KR101017060B1 - Biomarker to confirm exposure to toxaphene and verification method using the same - Google Patents

Abstract

The present invention relates to a biomarker for confirming exposure to toxaphene and a method of identifying the same, specifically, increase or decrease of gene expression in comparison to a control group by toxaphene, one of the residual organic contaminants. It relates to a biomarker and a method for confirming exposure to toxaphene using the same. The DNA microarray chip incorporating the biomarker of the present invention can be usefully used to determine toxaphene exposure to human liver, and can be used as a tool for identifying the mechanism of toxic action induced by toxaphene.

Toxaphene, Persistent Organic Contaminants, Insecticides, Biomarkers, DNA Microarray Chips

Description

Biomarker for confirming exposure to toxaphene and identification method using the same {Biomarker for identification of exposure to toxaphene and the method of identification using descriptor}

The present invention relates to a biomarker for confirming exposure to toxaphene and a method of identifying the same.

Toxaphene, one of persistent organic contaminants, is mainly used as a pesticide such as insecticides and herbicides. Persistent organic contaminants are chemicals that accumulate in living organisms along thousands of miles of mobility and food chains, and continue to exist in the environment, causing harm to plants, animals, and humans (James CY et. al . , Ecotoxicol . environ . saf , 72: 162-172, 2009). Toxaphene has been reported to be toxic to nervous system damage, cancer causing, immunotoxicity, endocrine disorders, and the entire organ system of the human body, and is mainly known as a substance showing tumor promoter. Toxaphene has a good effect as a pesticide, but it was banned in 1980 in the United States due to the risk of mutations and bioaccumulation, but is still used in Central and South America, Africa, Eastern Europe and Asia (James CY). et al ., Ecotoxicol . environ . saf , 72: 162-172, 2009).

Studies on the tumor development mechanism and activation of toxaphene are being conducted. In this regard, studies on the binding of the estrogen receptor, the aryl hydrocarbon receptor (AHR), and the toxaphene have been conducted. (Eva C.Bonefeld jØrgensen et al . , Carcinogenesis , 18 (8): 1651-1654, 1997). Toxaphene can be used in vivo with MCF-7 cells, a human breast cancer cell line. vivo ) Experiments have been reported to increase the activity of ESR1 and ESR2 proteins by binding to the estrogen receptor alpha (ESR1) and the beta-type estrogen receptor beta (ESR2) (Ramamoorthy K et. al . , Endocrinology , 138 (4): 1520-1527, 1997). Mainly in vivo In the experiment, the detection of toxaphene in human milk and urine samples was investigated (Sten GA). et al ., Environ. Sci . Tecnol ., 26 (1992) 1838-1840), Toxaphene has been reported to be highly toxic in experiments with fish (Oehme M et. al . , Sci Total Environ ., 186 (1996) 13-24; Muir d et al ., Trends Anal . Chem ., 14 (1995) 56-66). Animal studies have been shown to cause liver or thyroid cancer (Steinel HH et al ., Mutation Res ., 230: 29-33, 1990). In mouse and guinea pigs, changes in body weight, enzyme activity in brain, liver, and kidney were observed (Chandra J). et al ., Indian J. Med . Res., 93: 193-1981, 1993).

Although some studies of estrogen-like activity and hormone receptor binding, gene expression changes, and animal experiments of persistent organic contaminants have been reported, they are mostly limited to studies related to monitoring human breast cancer cells and tissues and biological samples. And as mentioned above, there is not enough risk assessment data in the human body even if the toxaphene may cause disorders in human liver, and the detection method for exposure is also Gas Chromatography-Mass Spectrometer (GC-MS). Or classical methods such as High Performance Liquid Chromatography (HPLC). When using the GC-MS or HPLC method, quantitative analysis is possible, but appropriate conditions for analysis must be set, and expensive equipment is required. Therefore, faster and easier screening methods, such as real-time reverse transcription polymerase chain reaction (RT-PCR) or DNA microarray chips using primers, can be used to quickly assess the human body. It is an important task to identify and utilize molecular indicators that can detect the toxic effects in Esau, and to take appropriate measures and control against toxaphene exposure.

Several genome sequencing projects, including six mammals and 292 microbes, have been completed and reported to the National Center for Biotechnology Information (NCBI). Genome-wide expression studies are being conducted to study the function of genes based on the vast amount of data obtained. In other words, DNA microarray analysis was performed to analyze the expression of thousands of genes in one experiment (Schena M). et al ., Proc . Natl . Acad . Sci . USA 93: 10614-10619, 1996). Microarrays integrate a set of oligonucleotides of complementary DNA (cDNA) or 20-25 base pairs length into glass. cDNA microarrays are produced by labs in schools or by companies such as Agilent and Genomic Solutions, either mechanically immobilizing the cDNA collection on a chip or by using ink jetting (Sellheyer K). et al ., J. Am . Acad . Dermatol . 51: 681-692, 2004). Oligonucleotide microarrays are made by Affymetrix by direct synthesis on a chip using photolithography, and Agillent et al. Are produced by immobilizing synthesized oligonucleotides (Sellheyer K). et al ., J. Am . Acad . Dermatol . 51: 681-692, 2004).

For analysis of gene expression, RNA is obtained from a sample such as tissue, labeled with fluorescence or isotope, converted to cDNA, and hybridized with oligonucleotides in a DNA microarray. Oligomicroarrays mainly label the control and experimental groups with two different fluorescences (eg Cy3 and Cy5), perform hybridization on the same chip at the same time, and then optically scan the image to obtain fluorescence intensity and analyze the results. . Gene expression is determined by the ratio of the two fluorescence intensities (Somasundaram K et al ., Genomics Proteomics I: 1-10, 2002). In combination with the recent research on toxic genomics (Toxicogenomics), which is an advanced technique using DNA macroarray technology, high-throughput expression in specific tissues or cell lines by all chemicals including drug and new drug candidates, as well as representative environmental pollutants Analysis and quantitative analysis of the expression patterns of genes are now possible. Accordingly, by analyzing the frequency of expression of specific genes in specific cells, it is possible to discover genes related to adverse effects of drugs and harmful effects of environmental pollutants. The molecular mechanisms will be understood, and further, the search for substances that cause toxicity and side effects will be possible.

Accordingly, the present inventors observed and analyzed a gene expression profile in HepG2 cell line of human liver cancer cells exposed to toxaphene using oligomicroarrays in which 45,220 fragments of human genes were accumulated, thereby being specific to toxaphene compared to the control group. The present invention was completed by establishing a biomarker capable of confirming the exposure of toxaphene and a method of identifying the exposure using the same, by discovering a gene whose gene expression is increased or decreased.

An object of the present invention is to provide a biomarker for confirming the exposure to toxaphene.

Another object of the present invention is to provide a microarray chip for confirming exposure to toxaphene, in which the biomarker is integrated.

Another object of the present invention is to provide a method for detecting the biomarker for confirming exposure to toxaphene.

Another object of the present invention is to provide a kit for confirming exposure to toxaphene using the biomarker.

In order to achieve the above object, the present invention provides a biomarker for confirming the exposure to toxaphene, characterized in that the expression changes by the exposure to the residual organic toxin (Toxaphene).

In addition, the present invention, the nucleic acid sequence of any one or more genes selected from the biomarker; Or an oligonucleotide that is a fragment of the gene; Or it provides a microarray chip for confirming the exposure to toxaphene, the complementary strand molecules thereof.

In addition, the present invention provides a method for detecting the marker for confirming the exposure to toxaphene.

In addition, the present invention provides a kit for confirming exposure to toxaphene using the biomarker.

Hereinafter, the present invention will be described in detail.

The present invention provides a biomarker for confirming exposure to toxaphene, which is characterized by causing a change in expression by exposure to persistent organic contaminant toxaphene.

The biomarker is a gene whose expression is changed in the concentration treatment group of 80% of the cell survival of toxaphene, the p-value corresponds to 0.001 or less, and the expression is increased by 5 times or more or decreased by 0.2 times or less. The functions of genes in the classification of biological processes are as follows: developmental process, multicellular organismal development, response to stress, regulation of biological quality. Cell proliferation, apoptosis, cell cycle, cell morphogenesis, angiogenesis, growth, hemopoesis, coagulation It consists of the sterol metabolic process, spindle checkpoints and related genes.

The present invention provides a biomarker, characterized in that selected from the group consisting of:

Genebank XM_939547 (zinc finger protein 697), Genebank U51869 [Human proto-oncogene Bcd orf1 and orf2 mRNA, complete cds.  (U51869)], Genebank NR_002834 (dual specificity phosphatase 5 pseudogene), Genebank NM_207337 [antagonist of mitotic exit network 1 homolog (S.  cerevisiae)], Genebank NM_203472 (selenoprotein S), Genebank NM_203403 (chromosome 9 open reading frame 150), Genebank NM_203380 (acyl-CoA synthetase long-chain family member 5 ), Genebank NM_199330 [homer homolog 2 (Drosophila)], Genebank NM_182491 (zinc finger, AN1-type domain 2A), Genebank NM_181727 (spermatogenesis associated 12), Genebank NM_178234 (tumor suppressor candidate 3), Genebank NM_153020 (RNA binding motif protein 24), Genebank NM_152995 (nuclear transcription factor, X-box binding-like 1), Genebank NM_152673 (mucin 20, cell surface associated), Genebank NM_145906 {Homo sapiens RIO kinase 3 (yeast) (RIOK3), transcript variant 2, mRNA [NM_145906]}, gene registration number ( Genebank) NM_145904 (high mobility group AT-hook 1), genes, etc. Genebank NM_144497 [A kinase (PRKA) anchor protein (gravin) 12], Genebank NM_080927 (discoidin, CUB and LCCL domain containing 2), Genebank NM_080655 (chromosome 9 open reading frame 30), Genebank NM_080388 (S100 calcium binding protein A16), Genebank NM_052871 (hypothetical protein MGC4677), Genebank NM_033027 (AXIN1 up-regulated 1), Gene Registration Number Genebank NM_032717 (lung cancer metastasis-associated protein), Genebank NM_031459 (sestrin 2), Genebank NM_031412 [GABA (A) receptor-associated protein like 1)], Gene Registration Number ( Genebank) NM_030627 (cytoplasmic polyadenylation element binding protein 4), Genebank NM_024854 (hypothetical protein FLJ22028), Genebank NM_024713 (chromosome 15 open reading frame 29), Genebank NM_024580 (elongation) factor Tu GTP binding domain containing 1), Genebank NM_024345 (WD repeat domain 32), Genebank NM_022818 (microtubule-associated protein 1 light chain 3 beta), Genebank NM_022157 (Ras- related GTP binding C), Genebank NM_021928 [signal peptidase complex subunit 3 homolog (S.  cerevisiae)], Genebank NM_021158 [tribbles homolog 3 (Drosophila)], Genebank NM_021103 (thymosin, beta 10), Genebank NM_020362 (chromosome 1 open reading frame 128), Genebank No. NM_019556 (motile sperm domain containing 1), Genebank No. NM_018590 (chondroitin sulfate GalNAcT-2), Genebank No. NM_018361 [1-acylglycerol-3-phosphate O-acyltransferase 5 ( lysophosphatidic acid acyltransferase, epsilon)], Genebank NM_017556 (filamin binding LIM protein 1), Genebank NM_016950 [sparc / osteonectin, cwcv and kazal-like domains proteoglycan (testican) 3], Gene registration Genebank NM_016470 (chromosome 20 open reading frame 111), Genebank NM_016131 (RAB10, member RAS oncogene family), Genebank NM_015167 (jumonji domain containing 6), Genebank (Genebank) NM_014685 (homocysteine -inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1), Genebank NM_014624 (S100 calcium binding protein A6), Genebank NM_014331 [solute carrier family 7, (cationic amino acid transporter , y + system) member 11], Genebank NM_014059 (chromosome 13 open reading frame 15), Genebank NM_013320 (host cell factor C2), Genebank NM_013259 (transgelin 3), Genebank NM_012394 (prefoldin subunit 2), Genebank NM_012258 (hairy / enhancer-of-split related with YRPW motif 1), Genebank NM_012154 (eukaryotic translation initiation factor 2C, 2 ), Genebank NM_012110 (cysteine-rich hydrophobic domain 2), Genebank NG_006644 (heat shock 105kDa / 110kDa protein 1), Genebank NM_005843 [signal transducing adapter molecule (SH3 domain) and ITAM motif) 2], Genebank NM_005746 (pre-B-cell colony enhancing factor 1), Genebank NM_005347 [heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)], Genebank (Genebank) ) NM_005228 [epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)], gene registration number (Genebank) NM_005110 (glutamine-fructose-6-phosphate transaminase 2), gene registration number (Genebank) NM_005018 (programmed cell death 1), Genebank NM_004972 [Janus kinase 2 (a protein tyrosine kinase)], Genebank NM_004926 (zinc finger protein 36, C3H type-like 1), gene registration number (Genebank) NM_004925 [aquaporin 3 (Gill blood group)], gene registration number (Genebank) NM_004760 (serine / threonine kinase 17a), gene registration number (Genebank) NM_004666 (vanin 1), gene registration number (Genebank) NM_004417 (dual specificity phosphatase 1), Genebank NM_004398 [DEAD (Asp-Glu-Ala-Asp ) box polypeptide 10], Genebank NM_004171 [solute carrier family 1 (glial high affinity glutamate transporter), member 2], Genebank NM_004073 [olo-like kinase 3 (Drosophila)], Gene registration Genebank NM_004024 (activating transcription factor 3), Genebank NM_003979 (G protein-coupled receptor, family C, group 5, member A), Genebank NM_003937 [kynureninase (L-kynurenine hydrolase) )], Genebank NM_003897 (immediate early response 3), Genebank NM_003873 (neuropilin 1), Genebank NM_003806 [harakiri, BCL2 interacting protein (contains only BH3 domain)], Genebank NM_003608 (G protein-coupled receptor 65), Genebank NM_003407 [zinc finger protein 36, C3H type, homolog (mouse)], Genebank NM_003388 (CAP-GLY domain containing linker protein 2), Genebank ) NM_003254 (TIMP metallopeptidase inhibitor 1), Genebank NM_003122 (serine peptidase inhibitor, Kazal type 1), Genebank NM_003113 (SP100 nuclear antigen), Genebank NM_002436 (membrane protein, palmitoylated 1, 55 kDa), Genebank NM_002421 [matrix metallopeptidase 1 (interstitial collagenase)], Genebank NM_002394 [solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2], Genebank NM_002309 [leukemia inhibitory factor (cholinergic differentiation factor)], Genebank NM_002305 [lectin, galactoside-binding, soluble, 1 (galectin 1)], Genebank NM_002288 (leukocyte -associated immunoglobulin-like receptor 2), Genebank NM_002276 (keratin 19), Genebank NM_002224 (inositol 1,4,5-triphosphate receptor, type 3), Genebank NM_0022 03 [integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)], gene registration number (Genebank) NM_002143 (hippocalcin), gene registration number (Genebank) NM_002131 (high mobility group AT-hook 1), gene registration Number (Genebank) NM_002061 (glutamate-cysteine ligase, modifier subunit), gene registration number (Genebank) NM_002056 (glutamine-fructose-6-phosphate transaminase 1), gene registration number (Genebank) NM_002032 (ferritin, heavy polypeptide 1) Genebank NM_001902 [cystathionase (cystathionine gamma-lyase)], Genebank NM_001731 (B-cell translocation gene 1, anti-proliferative), Genebank NM_001730 [Kruppel-like factor 5 ( intestinal)], Genebank NM_001614 (actin, gamma 1), Genebank NM_001554 (cysteine-rich, angiogenic inducer, 61), Genebank NM_001421 [E74-like factor 4 ( ets domain transcription factor], Genebank NM_001013398 (insulin-like growth factor binding protein 3), Genebank NM_000641 (interleukin 11), Genebank NM_000602 [serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1], gene registration number Genebank NM_000584 (interleukin 8), Genebank NM_000574 [CD55 molecule, decay accelerating factor for complement (Cromer blood group)], Genebank NM_000433 [neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease) , autosomal 2)], Genebank NM_000259 [myosin VA (heavy chain 12, myoxin)], Genebank NM_000214 [jagged 1 (Alagille syndrome)], Genebank NM_000202 [iduronate 2-sulfatase (Hunter syndrome)], Genebank D55639 [Kynureninase (L-kynurenine hydrolase)], Genebank BG001037 (Thioredoxin reductase 1), Genebank BC070200 (hypothetical LOC541471) , Genes, etc. Number (Genebank) BC030702 (microcephaly, primary autosomal recessive 1), gene registration number (Genebank) BC005130 (hypothetical protein MGC11082), Genebank AF180519 [GABA (A) receptors associated protein like 3], gene registration number ( Genebank) AB007870 (nucleoporin like 1), Genebank XM_940101 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 11], Genebank XM_938617 {PREDICTED: Homo sapiens hypothetical protein LOC649542 (LOC649542), mRNA [XM_938617]}, Genebank XM_936688 {PREDICTED: Homo sapiens similar to Ceruloplasmin precursor (Ferroxidase) (LOC441368), mRNA [XM_926222]}, Gene accession number (Genebank) XM_935655 [R nucleotide exchange factor (GEF) 5, Genebank XM_372002 [amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2 pseudogene], Genebank U68494 [Solute carrier family 30 (zinc transporte) r), member 1], Genebank NR_002932 (glutathione S-transferase M1 pseudogene), Genebank NR_002187 (hypothetical protein LOC286016), Genebank NM_203481 (hypothetical LOC403340), Gene Registration Genebank NM_201523 (kinesin light chain 4), Gene Registration Number (Genebank) NM_199337 (similar to RIKEN cDNA 1810059G22), Genebank NM_199327 [sprouty homolog 1, antagonist of FGF signaling (Drosophila)], Gene Registration Number (Genebank) NM_198504 (progestin and adipoQ receptor family member IX), gene registration number (Genebank) NM_198252 [gelsolin (amyloidosis, Finnish type)], gene registration number (Genebank) NM_183075 (cytochrome P450, family 2, subfamily U, polypeptide 1), gene registration number (Genebank) NM_182908 [dehydrogenase / reductase (SDR family) member 2], gene registration number (Genebank) NM_182760 (sulfatase modifying factor 1), gene registration number (Genebank) NM_181738 (peroxiredoxin 2), gene registration time Genebank NM_177550 [solute carrier family 13 (sodium-dependent citrate transporter), member 5], Genebank NM_176787 (phosphatidylinositol glycan anchor biosynthesis, class N), Genebank NM_175887 (proline rich 15 ), Gene registration number (Genebank) NM_173500 (tau tubulin kinase 2), gene registration number (Genebank) NM_173216 (ST6 beta-galactosamide alpha-2,6-sialyltranferase 1), gene registration number (Genebank) NM_172350 (CD46 molecule, complement regulatory protein), Genebank NM_172234 {Homo sapiens interleukin 17 receptor B (IL17RB), transcript variant 2, mRNA [NM_172234]}, Genebank NM_172164 [nuclear autoantigenic sperm protein (histone-binding)] , Genebank NM_153631 (homeobox A3), Genebank NM_153482 {Homo sapiens interleukin 17 receptor E (IL17RE), transcript variant 4, mRNA [NM_153482]}, Genebank NM_153344 {Homo sapiens chromosome 6 op en reading frame 141 (C6orf141), mRNA [NM_153344], Genebank NM_153186 (ankyrin repeat domain 15), Genebank NM_152764 (chromosome 16 open reading frame 73), Genebank (Genebank) NM_152722 (hepatocyte cell adhesion molecule), Genebank NM_152718 (von Willebrand factor C and EGF domains), Genebank NM_152379 (chromosome 1 open reading frame 131), Genebank NM_152308 (chromosome 16 open reading frame 75), Genebank NM_152299 (non-SMC condensin II complex, subunit H2), Genebank NM_148979 (cathepsin H), Genebank NM_145740 (glutathione S-transferase A1), Genebank NM_144966 (FRAS1 related extracellular matrix 1), Genebank NM_144595 (SLAIN motif family, member 1), Genebank NM_138730 (high mobility group nucleosomal binding domain 3) , Gene registration Genebank NM_138476 (magnesium-dependent phosphatase 1), Genebank NM_130806 (relaxin / insulin-like family peptide receptor 2), Genebank NM_058186 (family with sequence similarity 3, member B), Genebank (Genebank) NM_057091 (artemin), Genebank (Genebank) NM_054113 (calcium and integrin binding family member 3), Genebank (Genebank) NM_052968 (apolipoprotein AV), Genebank (Genebank) NM_033515 (Rho GTPase activating protein 18), Genebank NM_033502 (transcriptional regulating factor 1), Genebank NM_033380 [collagen, type IV, alpha 5 (Alport syndrome)], Genebank NM_033133 (2 ' , 3'-cyclic nucleotide 3 'phosphodiesterase, Genebank NM_031966 (cyclin B1), Genebank NM_031942 (cell division cycle associated 7), Genebank NM_031311 (carboxypeptidase, vitellogenic- like), heredity Genebank NM_030919 (family with sequence similarity 83, member D), Genebank NM_024743 (UDP glucuronosyltransferase 2 family, polypeptide A3), Genebank NM_024709 (chromosome 1 open reading frame 115), Genebank NM_024103 [solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 23], Genebank number NM_021871 (fibrinogen alpha chain), gene number (Genebank) NM_021139 (UDP glucuronosyltransferase 2 family, polypeptide B4), gene number (Genebank) NM_021069 (sorbin and SH3 domain containing 2), Genebank NM_020995 (haptoglobin-related protein), Genebank NM_020548 [diazepam binding inhibitor (GABA receptor modulator, acyl-Coenzyme A binding protein)], Genebank NM_020530 (oncostatin M), Genebank NM_020248 (catenin, beta interacting protein 1), Genebank NM_019101 (apolipoprotein M), Genebank NM_018663 (peroxisomal membrane protein 2, 22kDa), gene Genebank NM_018647 (tumor necrosis factor receptor superfamily, member 19), Genebank NM_018571 [amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2], Gene accession number (Genebank) bank) NM_018410 (hypothetical protein DKFZp762E1312), Genebank NM_018136 [asp (abnormal spindle) homolog, microcephaly associated (Drosophila)], Genebank NM_017915 (chromosome 12 open reading frame 48), gene registration number (Genebank) NM_017899 (tescalcin), Genebank NM_017893 [sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4G], Genebank NM_017855 (odontogenic , ameloblast asssociated, Genebank NM_017779 (DEP domain containing 1), Genebank NM_017770 [elongation of very long chain fatty acids (FEN1 / Elo2, SUR4 / Elo3, yeast) -like 2], Genebank No. NM_017763 (ring finger protein 43), Genebank No. NM_017410 (homeobox C13), Genebank No. NM_016824 [adducin 3 (gamma)], Genebank No. NM_016619 (placenta) -specific 8), gene registration number ( Genebank) NM_016618 (lysine-rich coiled-coil 1), Genebank NM_016343 [centromere protein F, 350 / 400ka (mitosin)], Genebank NM_016297 (prenylcysteine oxidase 1), Gene Registration Number ( Genebank) NM_016256 (N-acetylglucosamine-1-phosphodiester alpha- N-acetylglucosaminidase), Gene Registration Number (Genebank) NM_015974 (crystallin, lambda 1), Gene Registration Number (Genebank) NM_015917 (glutathione S-transferase kappa 1), Gene Registration Genebank NM_015471 [NSL1, MIND kinetochore complex component, homolog (S.  cerevisiae)], Genebank NM_015385 (sorbin and SH3 domain containing 1), Genebank NM_015277 (neural precursor cell expressed, developmentally down-regulated 4-like), Genebank NM_015261 ( non-SMC condensin II complex, subunit D3), Genebank NM_015071 (Rho GTPase activating protein 26), Genebank NM_015008 (transmembrane and coiled-coil domain family 1), Genebank (Genebank) NM_014762 (24-dehydrocholesterol reductase), Genebank (Genebank) NM_014430 (cell death-inducing DFFA-like effector b), Gene Registration Number (Genebank) NM_014333 (cell adhesion molecule 1), Gene Registration Number (Genebank) NM_014298 {quinolinate phosphoribosyltransferase [nicotinate-nucleotide pyrophosphorylase (carboxylating)], Genebank NM_014176 [ubiquitin-conjugating enzyme E2T (putative)], Genebank NM_014109 (ATPase family, AAA domain containing 2), Genebank NM_013282 (ubiquitin-like, containing PHD and RING finger domains, 1), Genebank NM_012484 [hyaluronan-mediated motility receptor (RHAMM)], Genebank NM_012288 (translocation associated membrane protein 2), Genebank NM_007256 (solute carrier organic anion transporter family, member 2B1), Genebank NM_007111 (transcription factor Dp-1), Genebank NM_006876 (UDP-GlcNAc : betaGal beta-1,3-N-acetylglucosaminyltransferase 1), Genebank NM_006863 [leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 1], Genebank NM_006821 (acyl- CoA thioesterase 2), Genebank NM_006744 (retinol binding protein 4, plasma), Genebank NM_006579 [emopamil binding protein (sterol isomerase)], Genebank NM_006546 (insulin-like growth factor 2 mRNA bindi ng protein 1), Genebank NM_006472 (thioredoxin interacting protein), Genebank NM_006461 (sperm associated antigen 5), Genebank NM_006403 (neural precursor cell expressed, developmentally down-regulated 9 ), Genebank NM_006079 (Cbp / p300-interacting transactivator, with Glu / Asp-rich carboxy-terminal domain, 2), Genebank NM_006055 [LanC lantibiotic synthetase component C-like 1 (bacterial) ], Genebank NM_005940 [matrix metallopeptidase 11 (stromelysin 3)], Genebank NM_005915 (minichromosome maintenance complex component 6), Genebank NM_005767 (purinergic receptor P2Y, G-protein coupled) , 5), Genebank NM_005733 (kinesin family member 20A), Genebank NM_005631 [smoothened homolog (Drosophila)], Genebank NM_005573 (lamin B1), Genebank (Genebank) ) NM_005567 (lectin, galactoside-binding, soluble, 3 binding protein), Genebank NM_005566 (lactate dehydrogenase A), Genebank NM_005502 [ATP-binding cassette, sub-family A (ABC1), member 1], Genebank NM_005432 (X-ray repair complementing defective repair in Chinese hamster cells 3), Genebank NM_005271 (glutamate dehydrogenase 1), Genebank NM_005165 (aldolase C, fructose) -bisphosphate), Gene Registration Number (Genebank) NM_005143 (haptoglobin), Gene Registration Number (Genebank) NM_005063 [stearoyl-CoA desaturase (delta-9-desaturase)], Gene Registration Number (Genebank) NM_005045 (reelin), Gene Registration Number (Genebank) NM_005030 [polo-like kinase 1 (Drosophila)], gene accession number (Genebank) NM_005021 (ectonucleotide pyrophosphatase / phosphodiesterase 3), gene accession number (Genebank) NM_004884 (putative neuronal cell adhesion molecule), gene registration number (Genebank) ) NM_004772 (chromosome 5 open reading frame 13), Genebank NM_004701 (cyclin B2), Genebank NM_004683 [regucalcin (senescence marker protein-30)], Genebank NM_004640 (HLA-B associated transcript 1), Genebank NM_004591 [chemokine (CC motif) ligand 20], Genebank NM_004508 (isopentenyl-diphosphate delta isomerase 1), Genebank NM_004428 (ephrin-A1), Gene Accession number (Genebank) NM_004252 [solute carrier family 9 (sodium / hydrogen exchanger), member 3 regulator 1], gene access number (Genebank) NM_004164 (retinol binding protein 2, cellular), gene accession number (Genebank) NM_004107 (Fc fragment of IgG, receptor, transporter, alpha), Genebank NM_004086 [coagulation factor C homolog, cochlin (Limulus polyphemus)], Genebank NM_003713 (phosphatidic acid phosphatase type 2B), Genebank (Genebank) ) NM_003707 [RuvB-like 1 (E.  coli)], Genebank NM_003667 (leucine-rich repeat-containing G protein-coupled receptor 5), Genebank NM_003634 [nipsnap homolog 1 (C.  elegans)], Genebank NM_003559 (phosphatidylinositol-4-phosphate 5-kinase, type II, beta), Genebank NM_003488 [A kinase (PRKA) anchor protein 1], Genebank (Genebank) ) NM_003483 (high mobility group AT-hook 2), Genebank number (Genebank) NM_003270 (tetraspanin 6), Genebank number (Genebank) NM_003243 (transforming growth factor, beta receptor III), Genebank number (Menebank) NM_003216 (thyrotrophic embryonic factor, Genebank NM_003118 [secreted protein, acidic, cysteine-rich (osteonectin)], Genebank (Genebank) NM_003104 (sorbitol dehydrogenase), Genebank (Nene) NM_003022 (SH3 domain binding glutamic acid -rich protein like), Genebank NM_002998 (syndecan 2), Genebank NM_002959 (sortilin 1), Genebank NM_002860 (aldehyde dehydrogenase 18 family, member A1), Gene accession number (Genebank) NM_002758 (mitogen-activa ted protein kinase kinase 6), Genebank NM_002729 (hematopoietically expressed homeobox), Genebank NM_002630 [progastricsin (pepsinogen C)], Genebank NM_002611 (pyruvate dehydrogenase kinase, isozyme 2) , Genebank NM_002592 (proliferating cell nuclear antigen), Genebank NM_002567 (phosphatidylethanolamine binding protein 1), Genebank NM_002508 (nidogen 1), Genebank NM_002413 (microsomal glutathione S-transferase 2), Genebank NM_002389 (CD46 molecule, complement regulatory protein), Genebank NM_002388 (minichromosome maintenance complex component 3), Genebank NM_002358 [MAD2 mitotic arrest deficient -like 1 (yeast)], Genebank NM_002340 [lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase)], Genebank NM_002334 (low density li poprotein receptor-related protein 4), gene registration number (Genebank) NM_002317 (lysyl oxidase), gene registration number (Genebank) NM_002083 [glutathione peroxidase 2 (gastrointestinal)], gene registration number (Genebank) NM_001948 (dUTP pyrophosphatase), gene registration Number (Genebank) NM_001914 [cytochrome b5 type A (microsomal)], gene registration number (Genebank) NM_001872 [carboxypeptidase B2 (plasma)], gene registration number (Genebank) NM_001815 (carcinoembryonic antigen-related cell adhesion molecule 3), gene registration Genebank NM_001809 (centromere protein A), Genebank NM_001789 [cell division cycle 25 homolog A (S.  pombe), Genebank NM_001786 (cell division cycle 2, G1 to S and G2 to M), Genebank NM_001756 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6], Genebank NM_001712 [carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)], Genebank NM_001461 (flavin containing monooxygenase 5), Genebank NM_001444 [fatty acid binding protein 5 (psoriasis-associated)], Genebank NM_001412 (eukaryotic translation initiation factor 1A, X-linked), Genebank NM_001360 (7-dehydrocholesterol reductase), Genebank NM_001359 ( 2,4-dienoyl CoA reductase 1, mitochondrial), Genebank NM_001311 [cysteine-rich protein 1 (intestinal)], Genebank NM_001237 (cyclin A2), Genebank NM_001182 (Genebank) aldehyde dehydrogenase 7 family, member A1), Genebank NM_001150 [alanyl (membrane) aminopeptidase N, aminopeptidase M, microsomal aminopeptidase, CD13, p150)], Genebank NM_001134 (alpha-fetoprotein), Genebank (Genebank) ) NM_001116 (adenylate cyclase 9), Genebank (Genebank) NM_001077 (UDP glucuronosyltransferase 2 family, polypeptide B17), Genebank (Genebank) NM_001075 (UDP glucuronosyltransferase 2 family, polypeptide B10), Gene registration number (Genebank) NM_001074 UDP glucuronosyltransferase 2 family, polypeptide B7), genebank NG_001073 (UDP glucuronosyltransferase 2 family, polypeptide B11), genebank NM_001072 (UDP glucuronosyltransferase 1 family, polypeptide A6), generegistration number (Genebank1) (thymidylate synthetase), Genebank NM_001067 (topoisomerase (DNA) II alpha 170kDa), Genebank NM_001040152 (paternally expressed 10) Genebank NM_001024074 (histamine N-methyltransferase), Genebank NM_001017395 (transmembrane and coiled-coil domain family 1), Genebank NM_001012271 [baculoviral IAP repeat-containing 5 (survivin)], Genebank NM_001010983 (glycosyltransferase 8 domain containing 1), Genebank NM_001005414 {Homo sapiens ZW10 interactor (ZWINT), transcript variant 4, mRNA [NM_001005414]}, Genebank NM_001005333 (melanoma antigen family D, 1), Genebank NM_001004320 (hypothetical protein LOC392636), Genebank NM_001003845 (Sp5 transcription factor), Genebank NM_001001290 (solute carrier family 2 (facilitated glucose transporter) , member 9], Genebank NM_000953 {prostaglandin D2 receptor (DP)}, Genebank NM_000859 (3-hydroxy-3-methylglutaryl-Coenzyme A reductase), Gene Registration Number (Genebank) NM_000851 (glutathione S-transferase M5), Genebank NM_000847 (glutathione S-transferase A3), Gene Registration Number (Genebank) NM_000791 (dihydrofolate reductase), Gene Registration Number (Genebank) NM_000790 [dopa decarboxylase (dopa decarboxylase (Genebank) aromatic L-amino acid decarboxylase)], Genebank NM_000784 (cytochrome P450, family 27, subfamily A, polypeptide 1), Genebank NM_000716 (complement component 4 binding protein, beta), Gene accession number (Genebank) NM_000689 (aldehyde dehydrogenase 1 family, member A1), Genebank NM_000672 [alcohol dehydrogenase 6 (class V)], Genebank NM_000671 [alcohol dehydrogenase 5 (class III), chi polypeptide] , Genebank NM_000638 (vitronectin), Genebank NM_000624 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5], Genebank NM_000509 (fibrinogen gamma chain ), U Genebank NM_000495 [collagen, type IV, alpha 5 (Alport syndrome)], Genebank (Genebank) NM_000483 (apolipoprotein C-II), Genebank (Menebank) NM_000457 (hepatocyte nuclear factor 4, alpha) , Gene registration number (Genebank) NM_000384 [apolipoprotein B (including Ag (x) antigen)], gene registration number (Genebank) NM_000371 [transthyretin (prealbumin, amyloidosis type I)], gene registration number (Genebank) NM_000365 (triosephosphate isomerase 1 ), Genebank NM_000354 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 7], Genebank NM_000313 [protein S (alpha)], Gene Registration number (Genebank) ) NM_000301 (plasminogen), Gene Registration Number (Genebank) NM_000277 (phenylalanine hydroxylase), Gene Registration Number (Genebank) NM_000253 (microsomal triglyceride transfer protein), Gene Registration Number (Genebank) NM_000211 [integrin, beta 2 (complement component 3 receptor 3) and 4 subunit)], gene Genebank NM_000204 (complement factor I), Genebank NM_000185 [serpin peptidase inhibitor, clade D (heparin cofactor), member 1], Genebank NM_000166 (gap junction protein, beta 1, 32 kDa), Genebank NM_000142 [fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)], Genebank NM_000130 [coagulation factor V (proaccelerin, labile factor)], Genebank NM_000064 (complement component 3), gene registration number (Genebank) NM_000042 [apolipoprotein H (beta-2-glycoprotein I)], gene registration number (Genebank) NM_000040 (apolipoprotein C-III), gene registration number (Genebank) NM_000039 (apolipoprotein AI) ), Genebank NM_000029 [angiotensinogen (serpin peptidase inhibitor, clade A, member 8)], Genebank NM_000014 (alpha-2-macroglobulin), Genebank M10036 (triosephosphate isomerase 1 ), Gene Registration No. (Genebank) CR627122 [MRNA; cDNA DKFZp779M2422 (from clone DKFZp779M2422)], Genebank CR625412 [acidic (leucine-rich) nuclear phosphoprotein 32 family, member A], Genebank CR624291 (CDNA: FLJ22515 fis, clone HRC12122, highly similar to AF052101 Homo sapiens clone 23872 mRNA sequence), Genebank CR605719 [Full-length cDNA clone CS0DK002YG10 of HeLa cells Cot 25-normalized of Homo sapiens (human)], Genebank CR603982 [MRNA; cDNA DKFZp313B1017 (from clone DKFZp313B1017)], Genebank No. BX405503 (Alpha-fetoprotein), Genebank No. BU783246 (in01c10. y1 Human insulinoma Homo sapiens cDNA clone IMAGE: 6123258 5 'similar to SW: ADHX_HUMAN P11766 ALCOHOL DEHYDROGENASE CLASS III CHI CHAIN;, mRNA sequence. ), Genebank BM928667 (Transcribed locus), Genebank BF591978 [Apolipoprotein H (beta-2-glycoprotein I)], Genebank BC067900 (hypothetical LOC149837), Gene Registry Number ( Genebank) BC064969 (Acidic (leucine-rich) nuclear phosphoprotein 32 family, member A), Genebank BC050733 [ATP-binding cassette, sub-family C (CFTR / MRP), member 6], gene registration number ( Genebank BC050292 (MGC44478), Genebank BC039065 [alcohol dehydrogenase 6 (class V)], Genebank (Genebank) BC027988 (hypothetical protein LOC253842), Genebank BC006267 (asparaginase like 1), Genebank Number (Genebank) AK123483 (CDNA FLJ41489 fis, clone BRTHA2004582), Genebank Number (Genebank) AK095855 (CDNA clone IMAGE: 4513453), Genebank Number AF132203 (PRO1933), Genebank Number AF118092 ( predicted protein of HQ2061; Homo sapiens PRO2061 mRNA, complete cds. ), Genebank AF007149 (hypothetical protein LOC257407).

1) Biomarker genes whose expression is increased by exposure of toxaphene in the biomarkers are as follows:

Genebank XM_939547 (zinc finger protein 697), Genebank U51869 [Human proto-oncogene Bcd orf1 and orf2 mRNA, complete cds. (U51869)], Genebank NR_002834 (dual specificity phosphatase 5 pseudogene), Genebank NM_207337 [antagonist of mitotic exit network 1 homolog (S. cerevisiae)], Genebank NM_203472 ( selenoprotein S), Genebank NM_203403 (chromosome 9 open reading frame 150), Genebank NM_203380 (acyl-CoA synthetase long-chain family member 5), Genebank NM_199330 [(homer) homolog 2 (Drosophila)], Genebank NM_182491 (zinc finger, AN1-type domain 2A), Genebank NM_181727 (spermatogenesis associated 12), Genebank NM_178234 (tumor suppressor candidate 3 ), Genebank NM_153020 (RNA binding motif protein 24), Genebank NM_152995 (nuclear transcription factor, X-box binding-like 1), Genebank NM_152673 (mucin 20, cell surface associated), gene registration number (G enebank) NM_145906 {Homo sapiens RIO kinase 3 (yeast) (RIOK3), transcript variant 2, mRNA [NM_145906]}, Genebank NM_145904 (high mobility group AT-hook 1), Genebank NM_144497 [A kinase (PRKA) anchor protein (gravin) 12], Genebank NM_080927 (discoidin, CUB and LCCL domain containing 2), Genebank NM_080655 (chromosome 9 open reading frame 30), Gene registration Genebank NM_080388 (S100 calcium binding protein A16), Genebank NM_052871 (hypothetical protein MGC4677), Genebank NM_033027 (AXIN1 up-regulated 1), Genebank NM_032717 (lung cancer metastasis-associated protein, Genebank NM_031459 (sestrin 2), Genebank NM_031412 [GABA (A) receptor-associated protein like 1], Genebank NM_030627 (cytoplasmic polyadenylation element binding protein 4), Gene Registration Number (Geneban k) NM_024854 (hypothetical protein FLJ22028), Genebank NM_024713 (chromosome 15 open reading frame 29), Genebank NM_024580 (elongation factor Tu GTP binding domain containing 1), Genebank NM_024345 (WD repeat domain 32), Genebank No. NM_022818 (microtubule-associated protein 1 light chain 3 beta), Genebank No. NM_022157 (Ras-related GTP binding C), Genebank No. NM_021928 [signal peptidase complex subunit 3 homolog (S. cerevisiae)], Genebank NM_021158 [tribbles homolog 3 (Drosophila)], Genebank NM_021103 (thymosin, beta 10), Genebank NM_020362 (chromosome 1 open reading frame 128), Genebank No. NM_019556 (motile sperm domain containing 1), Genebank No. NM_018590 (chondroitin sulfate GalNAcT-2), Genebank No. NM_018361 [1-acylglycerol-3-phosphate O-acyltransferase 5 ( lysophosphatidic acid acyltransferase, epsilon)], Genebank NM_017556 (filamin binding LIM protein 1), Genebank NM_016950 [sparc / osteonectin, cwcv and kazal-like domains proteoglycan (testican) 3], Gene registration Genebank NM_016470 (chromosome 20 open reading frame 111), Genebank NM_016131 (RAB10, member RAS oncogene family), Genebank NM_015167 (jumonji domain containing 6), Genebank (Genebank) NM_014685 (homocysteine- inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1), Genebank NM_014624 (S100 calcium binding protein A6), Genebank NM_014331 [solute carrier family 7, (cationic amino acid transporter, y + system) member 11], Genebank NM_014059 (chromosome 13 open reading frame 15), Genebank NM_013320 (host cell factor C2), Genebank NM_013259 (transgelin 3), Gene Genebank NM_012394 (prefoldin subunit 2), Genebank NM_012258 (hairy / enhancer-of-split related with YRPW motif 1), Genebank NM_012154 (eukaryotic translation initiation factor 2C, 2) , Genebank NM_012110 (cysteine-rich hydrophobic domain 2), Genebank NM_006644 (heat shock 105kDa / 110kDa protein 1), Genebank NM_005843 [signal transducing adaptor molecule (SH3 domain and ITAM motif) 2 ], Genebank NM_005746 (pre-B-cell colony enhancing factor 1), Genebank NM_005347 [heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)], Genebank (Genebank) NM_005228 [epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)], gene registration number (Genebank) NM_005110 (glutamine-fructose-6-phosphate transaminase 2), gene registration number (Genebank) NM_005018 (programmed cell death 1), Genebank NM_004972 [Janus kinase 2 (a protein tyrosine kinase)], Genebank NM_004926 (zinc finger protein 36, C3H type-like 1), gene registration number ( Genebank) NM_004925 [aquaporin 3 (Gill blood group)], Genebank NM_004760 (serine / threonine kinase 17a), Genebank Number (Genebank) NM_004666 (vanin 1), Genebank Number (Genebank) NM_004417 (dual specificity) phosphatase 1), Genebank NM_004398 [DEAD (Asp-Glu-Ala-Asp) box polypeptide 10], Genebank NM_004171 [solute carrier family 1 (glial high affinity glutamate transporter), member 2], Genebank NM_004073 [olo-like kinase 3 (Drosophila)], Gene accession number (Genebank) NM_004024 (activating transcription factor 3), Genebank NM_003979 (G protein-coupled receptor, family C, group 5, member A), Genebank NM_003937 [kynureninase (L-kynurenine hydrolase) ], Genebank NM_003897 (immediate early response 3), Genebank NM_003873 (neuropilin 1), Genebank NM_003806 [harakiri, BCL2 interacting protein (contains only BH3 domain)], genes Genebank NM_003608 (G protein-coupled receptor 65), Genebank NM_003407 [zinc finger protein 36, C3H type, homolog (mouse)], Genebank NM_003388 (CAP-GLY domain containing linker protein 2), Genebank NM_003254 (TIMP metallopeptidase inhibitor 1), Genebank (Genebank) NM_003122 (serine peptidase inhibitor, Kazal type 1), Gene Registration Number (Genebank) NM_003113 (SP100 nuclear antigen), Gene Registration Number (Genebank) NM_002436 (membrane protein, palmitoylated 1, 55 kDa), Genebank NM_002421 [matrix metallopeptidase 1 (interstitial collagenase)], Genebank NM_002394 [solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2], gene Genebank NM_002309 [leukemia inhibitory factor (cholinergic differentiation factor)], Genebank NM_002305 [lectin, galactoside-binding, soluble, 1 (galectin 1)], Genebank NM_002288 (leukocyte- associated immunoglobulin-like receptor 2), genebank NM_002276 (keratin 19), genebank NM_002224 (inositol 1,4,5-triphosphate receptor, type 3), genebank NM_0022 03 [integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)], gene registration number (Genebank) NM_002143 (hippocalcin), gene registration number (Genebank) NM_002131 (high mobility group AT-hook 1), gene registration Number (Genebank) NM_002061 (glutamate-cysteine ligase, modifier subunit), gene registration number (Genebank) NM_002056 (glutamine-fructose-6-phosphate transaminase 1), gene registration number (Genebank) NM_002032 (ferritin, heavy polypeptide 1) Genebank NM_001902 [cystathionase (cystathionine gamma-lyase)], Genebank NM_001731 (B-cell translocation gene 1, anti-proliferative), Genebank NM_001730 [Kruppel-like factor 5 ( intestinal)], Genebank NM_001614 (actin, gamma 1), Genebank NM_001554 (cysteine-rich, angiogenic inducer, 61), Genebank NM_001421 [E74-like factor 4 ( ets domain transcription factor], Genebank NM_001013398 (insulin-like growth factor binding protein 3), Genebank NM_000641 (interleukin 11), Genebank NM_000602 [serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1], gene registration number Genebank NM_000584 (interleukin 8), Genebank NM_000574 [CD55 molecule, decay accelerating factor for complement (Cromer blood group)], Genebank NM_000433 [neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease) , autosomal 2)], Genebank NM_000259 [myosin VA (heavy chain 12, myoxin)], Genebank NM_000214 [jagged 1 (Alagille syndrome)], Genebank NM_000202 [iduronate 2-sulfatase (Hunter syndrome)], Genebank D55639 [Kynureninase (L-kynurenine hydrolase)], Genebank BG001037 (Thioredoxin reductase 1), Genebank BC070200 (hypothetical LOC541471) , Gene registration Number (Genebank) BC030702 (microcephaly, primary autosomal recessive 1), gene registration number (Genebank) BC005130 (hypothetical protein MGC11082), Genebank AF180519 [GABA (A) receptors associated protein like 3], gene registration number ( Genebank) AB007870 (nucleoporin like 1).

2) Among the biomarkers, biomarker genes whose expression is reduced by exposure of toxaphene are as follows:

Genebank XM_940101 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 11], Genebank XM_938617 {PREDICTED: Homo sapiens hypothetical protein LOC649542 (LOC649542), mRNA [XM_938617] }, Genebank XM_936688 {PREDICTED: Homo sapiens similar to Ceruloplasmin precursor (Ferroxidase) (LOC441368), mRNA [XM_926222]}, Genebank XM_935655 [Rap guanine nucleotide exchange factor (GEF) 5], Genebank XM_372002 [amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2 pseudogene], Genebank U68494 [Solute carrier family 30 (zinc transporter), member 1], Genebank (Genebank) NR_002932 (glutathione S-transferase M1 pseudogene), Genebank NR_002187 (hypothetical protein LOC286016), Genebank NM_203481 (hypothetical LOC403340), Genebank NM_201523 (kinesin lig ht chain 4), Genebank NM_199337 (similar to RIKEN cDNA 1810059G22), Genebank NM_199327 [sprouty homolog 1, antagonist of FGF signaling (Drosophila)], Genebank NM_198504 (progestin) and adipoQ receptor family member IX), Genebank NM_198252 [gelsolin (amyloidosis, Finnish type)], Genebank NM_183075 (cytochrome P450, family 2, subfamily U, polypeptide 1), gene registration number ( Genebank) NM_182908 [dehydrogenase / reductase (SDR family) member 2], Genebank NM_182760 (sulfatase modifying factor 1), Genebank NM_181738 (peroxiredoxin 2), Genebank NM_177550 [solute carrier family 13 (sodium-dependent citrate transporter), member 5], Genebank NM_176787 (phosphatidylinositol glycan anchor biosynthesis, class N), Genebank NM_175887 (proline rich 15), Gene accession number (Genebank) ) N M_173500 (tau tubulin kinase 2), gene registration number (Genebank) NM_173216 (ST6 beta-galactosamide alpha-2,6-sialyltranferase 1), gene registration number (Genebank) NM_172350 (CD46 molecule, complement regulatory protein), gene registration number ( Genebank) NM_172234 {Homo sapiens interleukin 17 receptor B (IL17RB), transcript variant 2, mRNA [NM_172234]}, Genebank NM_172164 [nuclear autoantigenic sperm protein (histone-binding)], Genebank number NM_153631 (homeobox A3), Genebank NM_153482 {Homo sapiens interleukin 17 receptor E (IL17RE), transcript variant 4, mRNA [NM_153482]}, Genebank NM_153344 {Homo sapiens chromosome 6 open reading frame 141 ( C6orf141), mRNA [NM_153344]}, Genebank NM_153186 (ankyrin repeat domain 15), Genebank NM_152764 (chromosome 16 open reading frame 73), Genebank NM_152722 (hepatocyte cell adhesion molecule), gene registration Genebank NM_152718 (von Willebrand factor C and EGF domains), Genebank NM_152379 (chromosome 1 open reading frame 131), Genebank NM_152308 (chromosome 16 open reading frame 75), Gene accession number (Genebank) NM_152299 (non-SMC condensin II complex, subunit H2), Gene Registration Number (Genebank) NM_148979 (cathepsin H), Gene Registration Number (Genebank) NM_145740 (glutathione S-transferase A1), Gene Registration Number (Genebank) NM_144966 (FRAS1 related extracellular matrix 1), Genebank NM_144595 (SLAIN motif family, member 1), Genebank NM_138730 (high mobility group nucleosomal binding domain 3), Genebank NM_138476 (magnesium -dependent phosphatase 1), Genebank NM_130806 (relaxin / insulin-like family peptide receptor 2), Genebank NM_058186 (family with sequence similarity 3, member B), Genebank NM_057091 (artemin), Genebank NM_054113 (calcium and integrin binding family member 3), Genebank NM_052968 (apolipoprotein AV), Genebank NM_033515 (Rho GTPase activating protein 18), Genebank (Genebank) NM_033502 (transcriptional regulating factor 1), Genebank NM_033380 [collagen, type IV, alpha 5 (Alport syndrome)], Genebank NM_033133 (2 ', 3'-cyclic nucleotide 3' phosphodiesterase), Genebank (Genebank) NM_031966 (cyclin B1), Genebank (Genebank) NM_031942 (cell division cycle associated 7), Genebank (Genebank) NM_031311 (carboxypeptidase, vitellogenic-like), Genebank NM_030919 ( family with sequence similarity 83, member D), Genebank NM_024743 (UDP glucuronosyltransferase 2 family, polypeptide A3), Genebank NM_024709 (chromosome 1 open reading frame 115), Genebank NM_02 4103 [solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 23], Genebank number NM_021871 (fibrinogen alpha chain), gene number (Genebank) NM_021139 (UDP glucuronosyltransferase 2 family, polypeptide B4), gene number (Genebank) NM_021069 (sorbin and SH3 domain containing 2), Genebank NM_020995 (haptoglobin-related protein), Genebank NM_020548 [diazepam binding inhibitor (GABA receptor modulator, acyl-Coenzyme A binding protein)], Genebank NM_020530 (oncostatin M), Genebank NM_020248 (catenin, beta interacting protein 1), Genebank NM_019101 (apolipoprotein M), Genebank NM_018663 (peroxisomal membrane protein 2, 22kDa), gene Genebank NM_018647 (tumor necrosis factor receptor superfamily, member 19), Genebank NM_018571 [amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2], gene registration number (Geneb) ank) NM_018410 (hypothetical protein DKFZp762E1312), Genebank NM_018136 [asp (abnormal spindle) homolog, microcephaly associated (Drosophila)], Genebank NM_017915 (chromosome 12 open reading frame 48), gene registration number (Genebank) NM_017899 (tescalcin), Genebank NM_017893 [sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4G], Genebank NM_017855 (odontogenic , ameloblast asssociated, Genebank NM_017779 (DEP domain containing 1), Genebank NM_017770 [elongation of very long chain fatty acids (FEN1 / Elo2, SUR4 / Elo3, yeast) -like 2] , Gene Registration Number (Genebank) NM_017763 (ring finger protein 43), Gene Registration Number (Genebank) NM_017410 (homeobox C13), Gene Registration Number (Genebank) NM_016824 [adducin 3 (gamma)], Gene Registration Number (Genebank) NM_016619 ( placenta-specific 8), gene registration number ( Genebank) NM_016618 (lysine-rich coiled-coil 1), Genebank NM_016343 [centromere protein F, 350 / 400ka (mitosin)], Genebank NM_016297 (prenylcysteine oxidase 1), Gene Registration Number ( Genebank) NM_016256 (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase), Gene Registration Number (Genebank) NM_015974 (crystallin, lambda 1), Gene Registration Number (Genebank) NM_015917 (glutathione S-transferase kappa 1), Gene Registration Genebank NM_015471 [NSL1, MIND kinetochore complex component, homolog (S. cerevisiae)], Genebank NM_015385 (sorbin and SH3 domain containing 1), Genebank NM_015277 (neural precursor cell expressed, developmentally down-regulated 4-like), Genebank NM_015261 ( non-SMC condensin II complex, subunit D3), Genebank NM_015071 (Rho GTPase activating protein 26), Genebank NM_015008 (transmembrane and coiled-coil domain family 1), Genebank (Genebank) NM_014762 (24-dehydrocholesterol reductase), Genebank (Genebank) NM_014430 (cell death-inducing DFFA-like effector b), Gene Registration Number (Genebank) NM_014333 (cell adhesion molecule 1), Gene Registration Number (Genebank) NM_014298 {quinolinate phosphoribosyltransferase [nicotinate-nucleotide pyrophosphorylase (carboxylating)], Genebank NM_014176 [ubiquitin-conjugating enzyme E2T (putative)], Genebank NM_014109 (ATPase family, AAA domain containing 2) , Genebank NM_013282 (ubiquitin-like, containing PHD and RING finger domains, 1), Genebank NM_012484 [hyaluronan-mediated motility receptor (RHAMM)], Genebank NM_012288 (translocation associated membrane protein 2), Genebank NM_007256 (solute carrier organic anion transporter family, member 2B1), Genebank NM_007111 (transcription factor Dp-1), Genebank NM_006876 (UDP- GlcNAc: betaGal beta-1,3-N-acetylglucosaminyltransferase 1), Genebank NM_006863 [leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 1], Genebank NM_006821 (acyl CoA thioesterase 2), Genebank NM_006744 (retinol binding protein 4, plasma), Genebank NM_006579 [emopamil binding protein (sterol isomerase)], Genebank NM_006546 (insulin-like growth factor 2 mRNA bindi ng protein 1), Genebank NM_006472 (thioredoxin interacting protein), Genebank NM_006461 (sperm associated antigen 5), Genebank NM_006403 (neural precursor cell expressed, developmentally down-regulated 9), Genebank NM_006079 (Cbp / p300-interacting transactivator, with Glu / Asp-rich carboxy-terminal domain, 2), Genebank NM_006055 [LanC lantibiotic synthetase component C-like 1 (bacterial) )], Genebank NM_005940 [matrix metallopeptidase 11 (stromelysin 3)], Genebank NM_005915 (minichromosome maintenance complex component 6), Genebank NM_005767 (purinergic receptor P2Y, G-protein) coupled, 5), Genebank NM_005733 (kinesin family member 20A), Genebank NM_005631 [smoothened homolog (Drosophila)], Genebank NM_005573 (lamin B1), Gene Registration Number ( Genebank) NM_005567 (lectin, galactoside-binding, soluble, 3 binding protein), Genebank NM_005566 (lactate dehydrogenase A), Genebank NM_005502 [ATP-binding cassette, sub-family A (ABC1), member 1], Genebank NM_005432 (X-ray repair complementing defective repair in Chinese hamster cells 3), Genebank NM_005271 (glutamate dehydrogenase 1), Genebank NM_005165 (aldolase C, fructose) -bisphosphate), Gene Registration Number (Genebank) NM_005143 (haptoglobin), Gene Registration Number (Genebank) NM_005063 [stearoyl-CoA desaturase (delta-9-desaturase)], Gene Registration Number (Genebank) NM_005045 (reelin), Gene Registration Number (Genebank) NM_005030 [polo-like kinase 1 (Drosophila)], gene accession number (Genebank) NM_005021 (ectonucleotide pyrophosphatase / phosphodiesterase 3), gene accession number (Genebank) NM_004884 (putative neuronal cell adhesion molecule), gene registration number (Genebank) ) NM_004772 (chromosom e 5 open reading frame 13), Genebank NM_004701 (cyclin B2), Genebank NM_004683 [regucalcin (senescence marker protein-30)], Genebank NM_004640 (HLA-B associated transcript 1), Genebank NM_004591 [chemokine (CC motif) ligand 20], Genebank NM_004508 (isopentenyl-diphosphate delta isomerase 1), Genebank NM_004428 (ephrin-A1), Genebank NM_004252 [solute carrier family 9 (sodium / hydrogen exchanger), member 3 regulator 1], Genebank NM_004164 (retinol binding protein 2, cellular), Genebank NM_004107 (Fc fragment of IgG, receptor, transporter, alpha), Genebank NM_004086 [coagulation factor C homolog, cochlin (Limulus polyphemus)], Genebank NM_003713 (phosphatidic acid phosphatase type 2B), gene registration number ( Genebank) NM_003707 [RuvB-like 1 (E. coli)], Genebank NM_003667 (leucine-rich repeat-containing G protein-coupled receptor 5), Genebank NM_003634 [nipsnap homolog 1 (C. elegans)], Genebank (Genebank) NM_003559 (phosphatidylinositol-4-phosphate 5-kinase, type II, beta), Genebank NM_003488 [A kinase (PRKA) anchor protein 1], Genebank NM_003483 (high mobility group AT-hook 2 ), Genebank NM_003270 (tetraspanin 6), Genebank NM_003243 (transforming growth factor, beta receptor III), Genebank NM_003216 (thyrotrophic embryonic factor), Genebank (Genebank) NM_003118 [secreted protein, acidic, cysteine-rich (osteonectin)], gene registration number (Genebank) NM_003104 (sorbitol dehydrogenase), gene registration number (Genebank) NM_003022 (SH3 domain binding glutamic acid-rich protein like), gene registration number ( Genebank) NM_002998 (syndecan 2), gene registration number (G enebank NM_002959 (sortilin 1), Genebank NM_002860 (aldehyde dehydrogenase 18 family, member A1), Genebank NM_002758 (mitogen-activated protein kinase kinase 6), Genebank NM_002729 (Genebank) hematopoietically expressed homeobox, Genebank NM_002630 [progastricsin (pepsinogen C)], Genebank NM_002611 (pyruvate dehydrogenase kinase, isozyme 2), Genebank NM_002592 (proliferating cell nuclear antigen), Genebank No. NM_002567 (phosphatidylethanolamine binding protein 1), Genebank No. NM_002508 (nidogen 1), Genebank No. NM_002413 (microsomal glutathione S-transferase 2), Genebank No. NM_002389 (Genebank) CD46 molecule, complement regulatory protein, Genebank NM_002388 (minichromosome maintenance complex component 3), Genebank NM_002358 [MAD2 mitotic arrest deficient -like 1 (yeast)], genebank NM_002340 [lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase)], genebank NM_002334 (low density lipoprotein receptor-related protein 4), gene registration Number (Genebank) NM_002317 (lysyl oxidase), gene registration number (Genebank) NM_002083 [glutathione peroxidase 2 (gastrointestinal)], gene registration number (Genebank) NM_001948 (dUTP pyrophosphatase), gene registration number (Genebank) NM_001914 [cytochrome b5 type A (microsomal)], Genebank NM_001872 [carboxypeptidase B2 (plasma)], Genebank NM_001815 (carcinoembryonic antigen-related cell adhesion molecule 3), Genebank NM_001809 (centromere protein A) , Genebank NM_001789 [cell division cycle 25 homolog A (S. pombe), Genebank NM_001786 (cell division cycle 2, G1 to S and G2 to M), Genebank NM_001756 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6], Genebank NM_001712 [carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)], Genebank NM_001461 (flavin containing monooxygenase 5), Genebank NM_001444 [fatty acid binding protein 5 (psoriasis-associated)], Genebank NM_001412 (eukaryotic translation initiation factor 1A, X-linked), Genebank NM_001360 (7-dehydrocholesterol reductase), Genebank NM_001359 ( 2,4-dienoyl CoA reductase 1, mitochondrial), Genebank NM_001311 [cysteine-rich protein 1 (intestinal)], Genebank NM_001237 (cyclin A2), Genebank NM_001182 (Genebank) aldehyde dehydrogenase 7 family, member A1), Genebank NM_001150 [alanyl (membrane) aminopeptidase N, aminopeptidase M, microsomal aminopeptidase, CD13, p150)], Genebank NM_001134 (alpha-fetoprotein), Genebank (Genebank) ) NM_001116 (adenylate cyclase 9), Genebank (Genebank) NM_001077 (UDP glucuronosyltransferase 2 family, polypeptide B17), Genebank (Genebank) NM_001075 (UDP glucuronosyltransferase 2 family, polypeptide B10), Gene registration number (Genebank) NM_001074 UDP glucuronosyltransferase 2 family, polypeptide B7), Genebank (Genebank) NM_001073 (UDP glucuronosyltransferase 2 family, polypeptide B11), Gene accession (Genebank) NM_001072 (UDP glucuronosyltransferase 1 family, polypeptide A6), Gene Registration Number (Genebank1) NM_ (thymidylate synthetase), Genebank NM_001067 (topoisomerase (DNA) II alpha 170kDa), Genebank NM_001040152 (paternally expressed 10) Genebank NM_001024074 (histamine N-methyltransferase), Genebank NM_001017395 (transmembrane and coiled-coil domain family 1), Genebank NM_001012271 [baculoviral IAP repeat-containing 5 (survivin)], Genebank NM_001010983 (glycosyltransferase 8 domain containing 1), Genebank NM_001005414 {Homo sapiens ZW10 interactor (ZWINT), transcript variant 4, mRNA [NM_001005414]}, Genebank NM_001005333 (melanoma antigen family D, 1), Genebank NM_001004320 (hypothetical protein LOC392636), Genebank NM_001003845 (Sp5 transcription factor), Genebank NM_001001290 (solute carrier family 2 (facilitated glucose transporter) , member 9], Genebank NM_000953 (prostaglandin D2 receptor (DP)), Genebank NM_000859 (3-hydroxy-3-methylglutaryl-Coenzyme A reductase), Gene Registration Number (Genebank) NM_000851 (glutathione S-transferase M5), Genebank NM_000847 (glutathione S-transferase A3), Gene Registration Number (Genebank) NM_000791 (dihydrofolate reductase), Gene Registration Number (Genebank) NM_000790 [dopa decarboxylase (dopa decarboxylase (Genebank) aromatic L-amino acid decarboxylase)], Genebank NM_000784 (cytochrome P450, family 27, subfamily A, polypeptide 1), Genebank NM_000716 (complement component 4 binding protein, beta), Gene accession number (Genebank) NM_000689 (aldehyde dehydrogenase 1 family, member A1), Genebank NM_000672 [alcohol dehydrogenase 6 (class V)], Genebank NM_000671 [alcohol dehydrogenase 5 (class III), chi polypeptide ], Genebank NM_000638 (vitronectin), Genebank NM_000624 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5], Genebank NM_000509 (fibrinogen gamma chain) Genebank NM_000495 [collagen, type IV, alpha 5 (Alport syndrome)], Genebank number (Genebank) NM_000483 (apolipoprotein C-II), Genebank number (Genebank) NM_000457 (hepatocyte nuclear factor 4, alpha) , Gene registration number (Genebank) NM_000384 [apolipoprotein B (including Ag (x) antigen)], gene registration number (Genebank) NM_000371 [transthyretin (prealbumin, amyloidosis type I)], gene registration number (Genebank) NM_000365 (triosephosphate isomerase 1 ), Genebank NM_000354 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 7], Genebank NM_000313 [protein S (alpha)], Genebank (Genebank) NM_000301 (plasminogen), Gene Registration Number (Genebank) NM_000277 (phenylalanine hydroxylase), Gene Registration Number (Genebank) NM_000253 (microsomal triglyceride transfer protein), Gene Registration Number (Genebank) NM_000211 [integrin, beta 2 (complement component 3 receptor 3 and 4 subunit)], gene Genebank NM_000204 (complement factor I), Genebank NM_000185 [serpin peptidase inhibitor, clade D (heparin cofactor), member 1], Genebank NM_000166 (gap junction protein, beta 1, 32 kDa), Genebank NM_000142 [fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)], Genebank NM_000130 [coagulation factor V (proaccelerin, labile factor)], Gene accession number (Genebank) NM_000064 (complement component 3), Genebank NM_000042 [apolipoprotein H (beta-2-glycoprotein I)], Genebank NM_000040 (apolipoprotein C-III), Genebank NM_000039 (apolipoprotein AI), gene registration number (Genebank) NM_000029 [angiotensinogen (serpin peptidase inhibitor, clade A, member 8)], gene registration number (Genebank) NM_000014 (alpha-2-macroglobulin), gene registration number (Genebank) M10036 (triosephosphate isomerase 1) Gene Registration No. (Genebank) CR627122 [MRNA; cDNA DKFZp779M2422 (from clone DKFZp779M2422)], Genebank CR625412 [acidic (leucine-rich) nuclear phosphoprotein 32 family, member A], Genebank CR624291 (CDNA: FLJ22515 fis, clone HRC12122, highly similar to AF052101 Homo sapiens clone 23872 mRNA sequence), Genebank CR605719 [Full-length cDNA clone CS0DK002YG10 of HeLa cells Cot 25-normalized of Homo sapiens (human)], Genebank CR603982 [MRNA; cDNA DKFZp313B1017 (from clone DKFZp313B1017)], Genebank number BX405503 (Alpha-fetoprotein), Gene accession number (Genebank) BU783246 (in01c10.y1 Human insulinoma Homo sapiens cDNA clone IMAGE: 6123258 5 'similar to SWMANAD11766_ ALCOHOL DEHYDROGENASE CLASS III CHI CHAIN;, mRNA sequence.), Genebank BM928667 (Transcribed locus), Genebank BG591978 [Apolipoprotein H (beta-2-glycoprotein I)], Genebank (Genebank) ) BC067900 (hypothetical LOC149837), Genebank BC064969 (Acidic (leucine-rich) nuclear phosphoprotein 32 family, member A), Genebank BC050733 [ATP-binding cassette, sub-family C (CFTR / MRP), member 6], gene registration number (Genebank) BC050292 (MGC44478), gene registration number (Genebank) BC039065 [alcohol dehydrogenase 6 (class V)], gene registration number (Genebank) BC027988 (hypothetical protein LOC253842), gene registration Number (Genebank) BC006267 (asparaginase like 1), Genebank AK123483 (CDNA FLJ41489 fis, clone BRTHA2004582), Genebank AK095855 (CDNA clone IMAGE: 4513453), Genebank AF132203 (PRO1933), Genebank AF118092 (Genebank) predicted protein of HQ2061; Homo sapiens PRO2061 mRNA, complete cds.), Genebank AF007149 (hypothetical protein LOC257407).

In order to discover a biomarker for confirming the exposure to toxaphene, the present inventors treated toxaphene with human liver cancer cell line (HepG2) to treat 80% viable toxin (IC20 dose) of toxaphene (see FIG. 1). After treatment, mRNA was isolated and analyzed for gene expression using 4X44 k oligomicroarray chip Human whole genome microarray (Agilent, USA) (see Figure 2). When the p-value was less than 0.001 and the Cy5 / Cy3 ratio was 5 times or more, the gene was classified as an increased expression, and when it was 0.2 or less, the gene was classified as a reduced gene. As a result, it was confirmed that the expression of the increased gene was 0.261% (118 of 45,220 genes), 0.599% (271 of 45,220 genes) reduced expression. Among the genes, genes whose functions are known are classified according to a biological process. As a result, the developmental process, multicellular organismal development, response to stress, and regulation of biological characteristics are regulated. of biological quality, cell proliferation, apoptosis, cell cycle, cell morphogenesis, angiogenesis, growth, hemopoiesis, Genes associated with coagulation, sterol metabolic processes, and spindle checkpoints (see Tables 2 and 3). The genes have not been reported to be associated with toxicity in human liver cancer cell lines when treated with the toxaphene used in the present invention.

In addition, the present invention, the nucleic acid sequence of any one or more genes selected from the biomarker; Or an oligonucleotide that is a fragment of the gene; Or it provides a microarray chip for confirming the exposure to toxaphene, the complementary strand molecules thereof.

The oligonucleotide or complementary strand molecule thereof comprises 15 to 50, preferably 15 to 30, more preferably 18 to 25 nucleic acids of the biomarker gene.

The DNA microarray chip of the present invention can be produced by methods known to those skilled in the art. The method of manufacturing the microarray chip is as follows. In order to immobilize the searched biomarker as a probe DNA molecule on a substrate of a DNA chip, a micropipetting method using a piezoelectric method or a pin type spotter is used. It is preferable to use a method and the like, but is not limited thereto. The substrate of the DNA microarray chip is preferably coated with one active group selected from the group consisting of amino-silane, poly-L-lysine, and aldehyde. It is not limited. In addition, the substrate may be selected from the group consisting of slide glass, plastic, metal, silicon, nylon membrane, and nitrocellulose membrane, but is not limited thereto.

The present invention also provides a method for detecting the marker for confirming exposure to toxaphene.

The present invention

RNA samples isolated from somatic cells of subjects (experimental group) and control subjects suspected of exposure to toxaphene.

1) labeling the experimental and control groups with different fluorescent materials while synthesizing with cDNA;

2) hybridizing cDNA labeled with different fluorescent materials of step 1) with the DNA microarray chip of the present invention;

3) analyzing the reacted DNA microarray chip of step 2); And

4) provides a method of detecting the biomarker to confirm exposure to toxaphene, comprising comparing the expression level of the gene on the DNA microarray chip with the control in the analyzed data of step 3). .

The somatic cell is preferably used, but is not limited to cells derived from liver or liver cancer cells and tissues. At this time, the control group will be a healthy individual.

In addition, the fluorescent material of step 2) is preferably selected from the group consisting of Cy3, Cy5, poly L-lysine-fluorescein isothiocyanate (FITC), rhodamine-B-isothiocyanate (RITC), and rhodamine (rhodamine). Not all phosphors known to those skilled in the art can be used. In addition, the hybridization of step 2) is preferably performed at 40 to 50 ° C. for 10 to 20 hours, but is not limited thereto.

In addition, the DNA microarray chip of step 2) can be used as long as the microarray chip is loaded with the over- or low-expression gene (see Table 2 and Table 3) in the human genome of the present invention, and Whole Human Genome Oligo Microarray (Agilent, USA) is preferably used, but is not limited thereto. It is most preferable to use a DNA microarray chip manufactured by the present inventors.

In addition, in the analysis of step 3), it is preferable that the hybridized microarray chip is washed, stained, scanned, subjected to image processing, and then statistical analysis. The staining and washing using the uidics Station 450, the scan using the GeneChip scanner ^® 3000, the image processing using the Affymetrix GeneChip ^® Operating System (GCOS), all procedures are preferably performed according to Affymetrix protocol It is not limited to this. The statistical analysis is preferably performed using GenPlex software version 2.3, but is not limited thereto. Analysis software known to those skilled in the art may be used.

In addition,

RNA samples isolated from somatic cells of subjects (experimental group) and control subjects suspected of exposure to toxaphene.

1) Real-time reverse transcript polymerase chain reaction (RT-PCR) is performed on the RNA of step 1) using primer pairs complementary to the biomarker gene of the present invention and capable of amplifying the biomarker gene. step; And

2) comparing the amount of the gene product of step 1) with the control group, to provide a method for detecting the biomarker to confirm the exposure to toxaphene.

The somatic cells are preferably ones using cells derived from liver or liver cancer cells and tissues, but are not limited thereto. At this time, the control group will be a healthy individual.

The primer pair of step 1) is in the forward direction of 15 to 50mers long, preferably 15 to 30mers long, more preferably 18 to 25mers, designed so that the amplification product of the biomarker gene is 100 to 300 bp. And reverse primer pairs are both available.

The present invention also provides a kit for diagnosing exposure to toxaphene, including the microarray chip.

In addition to the identification kit provides a diagnostic kit for exposure to toxaphene containing human somatic cells. The somatic cells can be used if the cells derived from the liver or liver cancer cells and tissues. The liver cancer cells preferably use HepG2, but are not limited thereto.

In addition, the kit may further include a fluorescent material, and the fluorescent material may be composed of a strepavidin-like phosphatease conjugate, a chemical fluorescence (chemiflurorensce), and a chemiluminescent material (chemiluminescent). It is preferably selected from the group but is not limited thereto.

In addition, the kit may further include a reaction reagent, the reaction reagent used for hybridization, reverse transcriptase for synthesizing cDNA from RNA, cNTPs and rNTP (premixed or separated feed), fluorescent staining agent It may be composed of a labeling reagent, such as a chemical inducing agent, a washing buffer, and the like, but is not limited thereto, and may include all reaction reagents required for hybridization of DNA microarray chips known to those skilled in the art.

In addition, the present invention provides a kit for diagnosing exposure to toxaphene, comprising a primer pair complementary to the biomarker gene and capable of amplifying the biomarker gene.

The primer pair of the identification kit is preferably selected from the group consisting of primer pairs 1 to 11, but is not limited thereto, and is 15 to 50mer in length so that the amplification product of the biomarker gene is 100 to 300 bp. Both forward and reverse primer pairs, preferably 15-30 mer long, more preferably 18-25 mer long, can be used.

Primer pair 1: forward primer set forth in SEQ ID NO: 1 and reverse primer set forth in SEQ ID NO: 2;

Primer pair 2: forward primer set forth in SEQ ID NO: 3 and reverse primer set forth in SEQ ID NO: 4;

Primer pair 3: forward primer set forth in SEQ ID NO: 5 and reverse primer set forth in SEQ ID NO: 6;

Primer pair 4: forward primer set forth in SEQ ID NO: 7 and reverse primer set forth in SEQ ID NO: 8;

Primer pair 5: forward primer set forth in SEQ ID NO: 9 and reverse primer set forth in SEQ ID NO: 10;

Primer pair 6: forward primer set forth in SEQ ID NO: 11 and reverse primer set forth in SEQ ID NO: 12;

Primer pair 7: forward primer set forth in SEQ ID NO: 13 and reverse primer set forth in SEQ ID NO: 14;

Primer pair 8: forward primer set forth in SEQ ID NO: 15 and reverse primer set forth in SEQ ID NO: 16;

Primer pair 9: forward primer set forth in SEQ ID NO: 17 and reverse primer set forth in SEQ ID NO: 18;

Primer pair 10: forward primer set forth in SEQ ID NO: 19 and reverse primer set forth in SEQ ID NO: 20; And,

Primer pair 11: Forward primer set forth in SEQ ID NO: 21 and reverse primer set forth in SEQ ID NO: 22.

In addition to the identification kit provides a diagnostic kit for exposure to toxaphene containing human somatic cells. The somatic cells can be used if the cells derived from the liver or liver cancer cells and tissues. The liver cancer cells preferably use HepG2, but are not limited thereto.

In addition, the kit may further include a reaction reagent, the reagent for labeling such as reverse transcriptase for synthesizing cDNA from RNA, cNTPs and rNTP (premixed or separated feed), chemical inducer of fluorescent dye, It may be composed of a washing buffer, etc., but is not limited thereto, and may include all reaction reagents required for the RT-PCR reaction known to those skilled in the art.

The DNA microarray chip incorporating the biomarker of the present invention can be usefully used to determine toxaphene exposure to human liver, and can be used as a tool for identifying the mechanism of toxic action induced by toxaphene.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

Example 1 Cell Culture and Chemical Treatment

<1-1> Cell Culture

Human liver cancer cell line HepG2 cells (Human hepatocellular liver carcinoma cell line) were incubated in DMEM medium (Gibro-BRL, USA) to which 5% FBS was added until 80% growth in 100 mm dish. The present inventors selected toxaphen, one of the persistent organic pollutants, through existing studies and reports, and dissolved it in DMSO. Vehicle concentration was less than 0.1% in all experiments.

<1-2> cytotoxicity test ( MTT assay ) And chemical processing

MTT experiment using HepG2 cell line was performed by the method of Mossman et al . ( J. Immunol . Methods , 65: 55-63, 1983). The DMEM medium of the 24-well plate was treated with 80 × 10 ⁴ / well cell number and treated with toxaphene dissolved in DMSO, and after 48 hours, MTT (3- [4,5-dimethylthiazol-2-yl] -2 , 5-diphenyltetra zolium bromide) 5 mg / ml were mixed and incubated at 37 ° C. for 3 hours. Thereafter, the medium was removed and the formed formazan crystal was dissolved in 500 µl of DMSO. Transfer to a 96-well plate was aliquoted and the OD value was measured at absorbance 540 nm. As a result of examining the cytotoxicity of toxaphene in the HepG2 cell line, the 80% survival concentration (IC20 dose) for the cells was 238 μM (see FIG. 1), and the microarray experiment was performed by determining the concentration.

< Example  2> Microarray  Experiment

<2-1> RNA Isolation and Labeling of Fluorescent Materials

After dispensing HepG2 cells in a 100 mm dish at a concentration of 6 × 10 ⁶ cells / ml, toxaphene at the concentration determined in Example 1-2 was treated for 48 hours. Thereafter, total RNA was isolated from the treated cells using a trizol reagent (Invitrogen life technologies, USA) according to the manufacturer's method, and purified using an RNeasy mini kit (Qiagen, USA). Genomic DNA was removed using RNase-free DNase set (Qiagen, USA) during RNA purification. The amount of each total RNA sample was measured by spectrophotometer, the concentration was confirmed by Experion (Automated Electrophoresis station, Bio-Rad, USA).

<2-2> Labeled cDNA  Produce

CDNA was prepared using total RNA of the toxaphene treated group obtained in Example 2-1 for oligo microarray analysis. Specifically, 30 μg of the obtained RNA and 2 μg (1 μg / μl) of oligo (dT) primer were mixed and reacted at 65 ° C. for 10 minutes, and then annealed in ice immediately. Reagents were mixed as shown in Table 1 for Reverse Transcript reaction of the annealed RNA.

Configuration Volume (μl) 5X first strand buffer 6 dNTPs 0.6 0.1 M DDT 3 SuperScript II enzyme 3 Cy-3 or Cy-5 dUTP 2

Total RNA isolated from the control HepG2 cell line was labeled with Cy3-dUTP (green), and RNA isolated from the toxin-treated HepG2 cell line was labeled with Cy5-dUTP (red). At this time, the two samples were mixed and purified using a Microcon YM-30 column (Millipore, USA).

<2-3> Hybridization  reaction

Hybridization and washing process was carried out according to the instructions of Gino Chek Co., Ltd. (Korea). Hybridization was performed in a 62 ° C. oven for 12 hours. As a DNA microarray chip, 4 × 44 k Whole Human Genome Oligo Microarray (Agilent, USA) was used. After the washing process (washing in 2 × SSC / 0.1% SDS for 2 minutes, 1 × SSC for 3 minutes and 0.2 × SSC for 2 minutes), the slides were dried by centrifugation at 800 rpm for 3 minutes.

<2-4> Fluorescence Image Acquisition

Hybridization images on the slides were scanned with the Genepix 4000B (Axon Instruments, USA). Chips washed with unbound genes were obtained with a fluorescence image using a laser fluorescence scanner. In this case, the green fluorescence image in the control group, the red fluorescence image represents the activity level of the gene specifically expressed in the experimental group, and the yellow fluorescence image means that the expression of the two groups does not have a large difference in complementary colors of green and red. Scanned images were analyzed with GenePix 4.1 software (Axon Instruments, USA) to obtain gene expression rates. From the data obtained by the method, marker genes for toxaphene were selected by classifying the genes with increased expression when the Cy5 / Cy3 ratio was 5 times or more and by the genes with reduced expression when 0.2 or less. At this time, p-value is 0.001 or less. In the present example, the selection of five or more genes in the present embodiment results in a too large number of genes when 1.5 or 2 times the genes are selected according to the conventional method, so that the reliability of the specific gene for toxaphene may be reduced. Now, more than five times the expression genes were selected and P-value is the same reason.

As a result, it was confirmed that the genes with increased expression were 0.261% (118 out of 45,220 genes) and the genes with reduced expression were 0.599% (271 out of 45,220 genes).

As a result of classifying the functions of the selected genes according to a biological process, as shown in Tables 2 and 3, a developmental process, multicellular organismal development, and stress response stress, regulation of biological quality, cell proliferation, apoptosis, cell cycle, cell morphogenesis, angiogenesis, growth genes related to growth, hemopoiesis, coagulation, sterol metabolic processes, and spindle checkpoints.

Genes with Increased Expression by Toxaphene Registration Number
(Genebank) Gene name gene
Abbreviation Median ratio 1) developmental process NM_080927 discoidin, CUB and LCCL domain containing 2 DCBLD2 5.72 NM_022157 Ras-related GTP binding C RRAGC 5.43 NM_021158 tribbles homolog 3 (Drosophila) TRIB3 16.89 NM_017556 filamin binding LIM protein 1 FBLIM1 5.35 NM_015167 jumonji domain containing 6 JMJD6 5.17 NM_014624 S100 calcium binding protein A6 S100A6 13.98 NM_013259 transgelin 3 TAGLN3 39.15 NM_012258 hairy / enhancer-of-split related with YRPW motif 1 HEY1 15.97 NM_005347 heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) HSPA5 5.98 NM_005228 epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) EGFR 13.80 NM_005018 programmed cell death 1 PDCD1 6.43 NM_004972 Janus kinase 2 (a protein tyrosine kinase) JAK2 5.44 NM_004926 zinc finger protein 36, C3H type-like 1 ZFP36L1 8.02 NM_004760 serine / threonine kinase 17a STK17A 5.22 NM_003897 immediate early response 3 IER3 19.46 NM_003873 neuropilin 1 NRP1 8.35 NM_003806 harakiri, BCL2 interacting protein (contains only BH3 domain) HRK 6.98 NM_003608 G protein-coupled receptor 65 GPR65 16.35 NM_003407 zinc finger protein 36, C3H type, homolog (mouse) ZFP36 10.15 NM_003254 TIMP metallopeptidase inhibitor 1 TIMP1 47.63 NM_002394 solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2 SLC3A2 18.81 NM_002309 leukemia inhibitory factor (cholinergic differentiation factor) LIF 15.92 NM_002305 lectin, galactoside-binding, soluble, 1 (galectin 1) LGALS1 10.50 NM_002276 keratin 19 KRT19 5.02 NM_002203 integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) ITGA2 17.81 NM_002061 glutamate-cysteine ligase, modifier subunit GCLM 9.43 NM_001731 B-cell translocation gene 1, anti-proliferative BTG1 6.20 NM_001730 Kruppel-like factor 5 (intestinal) KLF5 23.27 NM_001614 actin, gamma 1 ACTG1 5.23 NM_001554 cysteine-rich, angiogenic inducer, 61 CYR61 5.60 NM_001013398 insulin-like growth factor binding protein 3 IGFBP3 6.94 NM_000641 interleukin 11 IL11 9.69 NM_000602 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 SERPINE1 8.54 NM_000584 interleukin 8 IL8 6.81 NM_000214 jagged 1 (Alagille syndrome) JAG1 5.99 U51869 Human proto-oncogene Bcd orf1 and orf2 mRNA, complete cds. [U51869] 9.31 NM_033027 AXIN1 up-regulated 1 AXUD1 6.63 2) multicellular organismal development NM_015167 jumonji domain containing 6 JMJD6 5.17 NM_014624 S100 calcium binding protein A6 S100A6 13.98 NM_013259 transgelin 3 TAGLN3 39.15 NM_012258 hairy / enhancer-of-split related with YRPW motif 1 HEY1 15.97 NM_005228 epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) EGFR 13.80 NM_005018 programmed cell death 1 PDCD1 6.43 NM_004972 Janus kinase 2 (a protein tyrosine kinase) JAK2 5.44 NM_004926 zinc finger protein 36, C3H type-like 1 ZFP36L1 8.02 NM_003873 neuropilin 1 NRP1 8.35 NM_003608 G protein-coupled receptor 65 GPR65 16.35 NM_003407 zinc finger protein 36, C3H type, homolog (mouse) ZFP36 10.15 NM_003254 TIMP metallopeptidase inhibitor 1 TIMP1 47.63 NM_002309 leukemia inhibitory factor (cholinergic differentiation factor) LIF 15.92 NM_002305 lectin, galactoside-binding, soluble, 1 (galectin 1) LGALS1 10.50 NM_002276 keratin 19 KRT19 5.02 NM_002203 integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) ITGA2 17.81 NM_002061 glutamate-cysteine ligase, modifier subunit GCLM 9.43 NM_001731 B-cell translocation gene 1, anti-proliferative BTG1 6.20 NM_001730 Kruppel-like factor 5 (intestinal) KLF5 23.27 NM_001614 actin, gamma 1 ACTG1 5.23 NM_001554 cysteine-rich, angiogenic inducer, 61 CYR61 5.60 NM_001013398 insulin-like growth factor binding protein 3 IGFBP3 6.94 NM_000641 interleukin 11 IL11 9.69 NM_000602 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 SERPINE1 8.54 NM_000584 interleukin 8 IL8 6.81 NM_000214 jagged 1 (Alagille syndrome) JAG1 5.99 U51869 Human proto-oncogene Bcd orf1 and orf2 mRNA, complete cds. [U51869] 9.31 3) response to stress NM_005228 epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) EGFR 13.80 NM_003407 zinc finger protein 36, C3H type, homolog (mouse) ZFP36 10.15 NM_002203 integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) ITGA2 17.81 NM_002061 glutamate-cysteine ligase, modifier subunit GCLM 9.43 NM_000641 interleukin 11 IL11 9.69 NM_000602 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 SERPINE1 8.54 NM_000584 interleukin 8 IL8 6.81 NM_080927 discoidin, CUB and LCCL domain containing 2 DCBLD2 5.72 NM_021158 tribbles homolog 3 (Drosophila) TRIB3 16.89 NM_005347 heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) HSPA5 5.98 NM_203472 selenoprotein S 5.01 NM_153020 RNA binding motif protein 24 RBM24 13.32 NM_014685 homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1 HERPUD1 14.42 NM_006644 heat shock 105kDa / 110kDa protein 1 HSPH1 10.82 NM_004417 dual specificity phosphatase 1 DUSP1 14.96 NM_000574 CD55 molecule, decay accelerating factor for complement (Cromer blood group) CD55 10.09 BG001037 Thioredoxin reductase 1 5.89 4) regulation of biological quality NM_003407 zinc finger protein 36, C3H type, homolog (mouse) ZFP36 10.15 NM_002203 integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) ITGA2 17.81 NM_002061 glutamate-cysteine ligase, modifier subunit GCLM 9.43 NM_000641 interleukin 11 IL11 9.69 NM_000602 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 SERPINE1 8.54 NM_080927 discoidin, CUB and LCCL domain containing 2 DCBLD2 5.72 NM_203472 selenoprotein S 5.01 NM_000574 CD55 molecule, decay accelerating factor for complement (Cromer blood group) CD55 10.09 BG001037 Thioredoxin reductase 1 5.89 NM_004926 zinc finger protein 36, C3H type-like 1 ZFP36L1 8.02 NM_001731 B-cell translocation gene 1, anti-proliferative BTG1 6.20 NM_001554 cysteine-rich, angiogenic inducer, 61 CYR61 5.60 NM_001013398 insulin-like growth factor binding protein 3 IGFBP3 6.94 U51869 Human proto-oncogene Bcd orf1 and orf2 mRNA, complete cds. [U51869] 9.31 NM_022157 Ras-related GTP binding C RRAGC 5.43 NM_002394 solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2 SLC3A2 18.81 NM_002032 ferritin, heavy polypeptide 1 FTH1 5.49 5) cell proliferation NM_000641 interleukin 11 IL11 9.69 BG001037 Thioredoxin reductase 1 5.89 NM_001731 B-cell translocation gene 1, anti-proliferative BTG1 6.20 NM_001554 cysteine-rich, angiogenic inducer, 61 CYR61 5.60 NM_002032 ferritin, heavy polypeptide 1 FTH1 5.49 NM_005228 epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) EGFR 13.80 NM_000584 interleukin 8 IL8 6.81 NM_014624 S100 calcium binding protein A6 S100A6 13.98 NM_004972 Janus kinase 2 (a protein tyrosine kinase) JAK2 5.44 NM_003873 neuropilin 1 NRP1 8.35 NM_003254 TIMP metallopeptidase inhibitor 1 TIMP1 47.63 NM_002309 leukemia inhibitory factor (cholinergic differentiation factor) LIF 15.92 NM_001730 Kruppel-like factor 5 (intestinal) KLF5 23.27 NM_000214 jagged 1 (Alagille syndrome) JAG1 5.99 NM_005746 pre-B-cell colony enhancing factor 1 PBEF1 5.36 NM_001421 E74-like factor 4 (ets domain transcription factor) ELF4 8.22 6) apoptosis NM_001731 B-cell translocation gene 1, anti-proliferative BTG1 6.20 NM_004972 Janus kinase 2 (a protein tyrosine kinase) JAK2 5.44 NM_002061 glutamate-cysteine ligase, modifier subunit GCLM 9.43 NM_001013398 insulin-like growth factor binding protein 3 IGFBP3 6.94 NM_022157 Ras-related GTP binding C RRAGC 5.43 NM_021158 tribbles homolog 3 (Drosophila) TRIB3 16.89 NM_005347 heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) HSPA5 5.98 NM_015167 jumonji domain containing 6 JMJD6 5.17 NM_005018 programmed cell death 1 PDCD1 6.43 NM_003608 G protein-coupled receptor 65 GPR65 16.35 NM_002305 lectin, galactoside-binding, soluble, 1 (galectin 1) LGALS1 10.50 NM_004760 serine / threonine kinase 17a STK17A 5.22 NM_003897 immediate early response 3 IER3 19.46 NM_003806 harakiri, BCL2 interacting protein (contains only BH3 domain) HRK 6.98 NM_033027 AXIN1 up-regulated 1 AXUD1 6.63 7) cell morphogenesis NM_001731 B-cell translocation gene 1, anti-proliferative BTG1 6.20 NM_001013398 insulin-like growth factor binding protein 3 IGFBP3 6.94 NM_022157 Ras-related GTP binding C RRAGC 5.43 NM_001554 cysteine-rich, angiogenic inducer, 61 CYR61 5.60 NM_014624 S100 calcium binding protein A6 S100A6 13.98 NM_003873 neuropilin 1 NRP1 8.35 NM_001730 Kruppel-like factor 5 (intestinal) KLF5 23.27 NM_080927 discoidin, CUB and LCCL domain containing 2 DCBLD2 5.72 U51869 Human proto-oncogene Bcd orf1 and orf2 mRNA, complete cds. [U51869] 9.31 NM_002394 solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2 SLC3A2 18.81 NM_017556 filamin binding LIM protein 1 FBLIM1 5.35 8) angiogenesis NM_001731 B-cell translocation gene 1, anti-proliferative BTG1 6.20 NM_001554 cysteine-rich, angiogenic inducer, 61 CYR61 5.60 NM_003873 neuropilin 1 NRP1 8.35 NM_001730 Kruppel-like factor 5 (intestinal) KLF5 23.27 NM_000584 interleukin 8 IL8 6.81 NM_000214 jagged 1 (Alagille syndrome) JAG1 5.99 NM_000602 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 SERPINE1 8.54 9) growth NM_001731 B-cell translocation gene 1, anti-proliferative BTG1 6.20 NM_001554 cysteine-rich, angiogenic inducer, 61 CYR61 5.60 NM_001013398 insulin-like growth factor binding protein 3 IGFBP3 6.94 NM_022157 Ras-related GTP binding C RRAGC 5.43 NM_080927 discoidin, CUB and LCCL domain containing 2 DCBLD2 5.72 U51869 Human proto-oncogene Bcd orf1 and orf2 mRNA, complete cds. [U51869] 9.31 NM_002394 solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2 SLC3A2 18.81 10) hemopoiesis U51869 Human proto-oncogene Bcd orf1 and orf2 mRNA, complete cds. [U51869] 9.31 NM_000214 jagged 1 (Alagille syndrome) JAG1 5.99 NM_004972 Janus kinase 2 (a protein tyrosine kinase) JAK2 5.44 NM_000641 interleukin 11 IL11 9.69 NM_003254 TIMP metallopeptidase inhibitor 1 TIMP1 47.63 NM_003407 zinc finger protein 36, C3H type, homolog (mouse) ZFP36 10.15

Genes with Reduced Expression by Toxaphene Registration Number
(Genebank) Gene name gene
Abbreviation Median ratio 1) developmental process XM_935655 Rap guanine nucleotide exchange factor (GEF) 5 RAPGEF5 0.19 U68494 Solute carrier family 30 (zinc transporter), member 1 0.19 NM_199327 sprouty homolog 1, antagonist of FGF signaling (Drosophila) SPRY1 0.16 NM_181738 peroxiredoxin 2 PRDX2 0.16 NM_175887 proline rich 15 PRR15 0.18 NM_173216 ST6 beta-galactosamide alpha-2,6-sialyltranferase 1 ST6GAL1 0.12 NM_172234 Homo sapiens interleukin 17 receptor B (IL17RB), transcript variant 2, mRNA [NM_172234] 0.15 NM_172164 nuclear autoantigenic sperm protein (histone-binding) NASP 0.16 NM_153631 homeobox A3 HOXA3 0.19 NM_152722 hepatocyte cell adhesion molecule HEPACAM 0.06 NM_144966 FRAS1 related extracellular matrix 1 FREM1 0.09 NM_130806 relaxin / insulin-like family peptide receptor 2 RXFP2 0.12 NM_057091 artemin ARTN 0.18 NM_052968 apolipoprotein A-V APOA5 0.16 NM_033502 transcriptional regulating factor 1 TRERF1 0.16 NM_033133 2 ', 3'-cyclic nucleotide 3' phosphodiesterase CNP 0.19 NM_021871 fibrinogen alpha chain FGA 0.03 NM_020530 oncostatin M OSM 0.18 NM_020248 catenin, beta interacting protein 1 CTNNBIP1 0.17 NM_018647 tumor necrosis factor receptor superfamily, member 19 TNFRSF19 0.15 NM_017893 sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4G SEMA4G 0.08 NM_017855 odontogenic, ameloblast asssociated ODAM 0.11 NM_017410 homeobox C13 HOXC13 0.14 NM_016343 centromere protein F, 350 / 400ka (mitosin) CENPF 0.05 NM_015071 Rho GTPase activating protein 26 ARHGAP26 0.18 NM_014762 24-dehydrocholesterol reductase DHCR24 0.06 NM_014430 cell death-inducing DFFA-like effector b CIDEB 0.17 NM_014333 cell adhesion molecule 1 CADM1 0.06 NM_007111 transcription factor Dp-1 TFDP1 0.15 NM_006579 emopamil binding protein (sterol isomerase) EBP 0.16 NM_006472 thioredoxin interacting protein TXNIP 0.05 NM_006403 neural precursor cell expressed, developmentally down-regulated 9 NEDD9 0.08 NM_006079 Cbp / p300-interacting transactivator, with Glu / Asp-rich carboxy-terminal domain, 2 CITED2 0.11 NM_005940 matrix metallopeptidase 11 (stromelysin 3) MMP11 0.10 NM_005631 smoothened homolog (Drosophila) SMO 0.08 NM_005045 reelin RELN 0.13 NM_004428 ephrin-A1 EFNA1 0.19 NM_004164 retinol binding protein 2, cellular RBP2 0.13 NM_003713 phosphatidic acid phosphatase type 2B PPAP2B 0.11 NM_003707 RuvB-like 1 (E. coli) RUVBL1 0.07 NM_003483 high mobility group AT-hook 2 HMGA2 0.09 NM_003243 transforming growth factor, beta receptor III TGFBR3 0.04 NM_003118 secreted protein, acidic, cysteine-rich (osteonectin) SPARC 0.14 NM_002959 sortilin 1 SORT1 0.11 NM_002729 hematopoietically expressed homeobox HHEX 0.11 NM_002317 lysyl oxidase LOX 0.18 NM_001786 cell division cycle 2, G1 to S and G2 to M CDC2 0.10 NM_001712 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein) CEACAM1 0.18 NM_001444 fatty acid binding protein 5 (psoriasis-associated) FABP5 0.15 NM_001360 7-dehydrocholesterol reductase DHCR7 0.19 NM_001150 alanyl (membrane) aminopeptidase (aminopeptidase N, aminopeptidase M, microsomal aminopeptidase, CD13, p150) ANPEP 0.14 NM_001134 alpha-fetoprotein AFP 0.12 NM_001067 topoisomerase (DNA) II alpha 170kDa TOP2A 0.02 NM_001012271 baculoviral IAP repeat-containing 5 (survivin) BIRC5 0.13 NM_001005333 melanoma antigen family D, 1 MAGED1 0.14 NM_000953 prostaglandin D2 receptor (DP) PTGDR 0.12 NM_000859 3-hydroxy-3-methylglutaryl-Coenzyme A reductase HMGCR 0.16 NM_000301 plasminogen PLG 0.11 NM_000211 integrin, beta 2 (complement component 3 receptor 3 and 4 subunit) ITGB2 0.17 NM_000166 gap junction protein, beta 1, 32kDa GJB1 0.13 NM_000142 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) FGFR3 0.06 NM_000029 angiotensinogen (serpin peptidase inhibitor, clade A, member 8) AGT 0.05 BX405503 Alpha-fetoprotein 0.11 2) multicellular organismal development XM_935655 Rap guanine nucleotide exchange factor (GEF) 5 RAPGEF5 0.19 U68494 Solute carrier family 30 (zinc transporter), member 1 0.19 NM_199327 sprouty homolog 1, antagonist of FGF signaling (Drosophila) SPRY1 0.16 NM_175887 proline rich 15 PRR15 0.18 NM_173216 ST6 beta-galactosamide alpha-2,6-sialyltranferase 1 ST6GAL1 0.12 NM_172164 nuclear autoantigenic sperm protein (histone-binding) NASP 0.16 NM_153631 homeobox A3 HOXA3 0.19 NM_144966 FRAS1 related extracellular matrix 1 FREM1 0.09 NM_130806 relaxin / insulin-like family peptide receptor 2 RXFP2 0.12 NM_057091 artemin ARTN 0.18 NM_052968 apolipoprotein A-V APOA5 0.16 NM_033502 transcriptional regulating factor 1 TRERF1 0.16 NM_033133 2 ', 3'-cyclic nucleotide 3' phosphodiesterase CNP 0.19 NM_021871 fibrinogen alpha chain FGA 0.03 NM_020530 oncostatin M OSM 0.18 NM_020248 catenin, beta interacting protein 1 CTNNBIP1 0.17 NM_017893 sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4G SEMA4G 0.08 NM_017855 odontogenic, ameloblast asssociated ODAM 0.11 NM_017410 homeobox C13 HOXC13 0.14 NM_016343 centromere protein F, 350 / 400ka (mitosin) CENPF 0.05 NM_015071 Rho GTPase activating protein 26 ARHGAP26 0.18 NM_014762 24-dehydrocholesterol reductase DHCR24 0.06 NM_014333 cell adhesion molecule 1 CADM1 0.06 NM_007111 transcription factor Dp-1 TFDP1 0.15 NM_006579 emopamil binding protein (sterol isomerase) EBP 0.16 NM_006079 Cbp / p300-interacting transactivator, with Glu / Asp-rich carboxy-terminal domain, 2 CITED2 0.11 NM_005940 matrix metallopeptidase 11 (stromelysin 3) MMP11 0.10 NM_005631 smoothened homolog (Drosophila) SMO 0.08 NM_005045 reelin RELN 0.13 NM_004428 ephrin-A1 EFNA1 0.19 NM_004164 retinol binding protein 2, cellular RBP2 0.13 NM_003713 phosphatidic acid phosphatase type 2B PPAP2B 0.11 NM_003483 high mobility group AT-hook 2 HMGA2 0.09 NM_003243 transforming growth factor, beta receptor III TGFBR3 0.04 NM_003118 secreted protein, acidic, cysteine-rich (osteonectin) SPARC 0.14 NM_002959 sortilin 1 SORT1 0.11 NM_002729 hematopoietically expressed homeobox HHEX 0.11 NM_002317 lysyl oxidase LOX 0.18 NM_001712 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein) CEACAM1 0.18 NM_001444 fatty acid binding protein 5 (psoriasis-associated) FABP5 0.15 NM_001360 7-dehydrocholesterol reductase DHCR7 0.19 NM_001150 alanyl (membrane) aminopeptidase (aminopeptidase N, aminopeptidase M, microsomal aminopeptidase, CD13, p150) ANPEP 0.14 NM_001134 alpha-fetoprotein AFP 0.12 NM_000953 prostaglandin D2 receptor (DP) PTGDR 0.12 NM_000859 3-hydroxy-3-methylglutaryl-Coenzyme A reductase HMGCR 0.16 NM_000301 plasminogen PLG 0.11 NM_000211 integrin, beta 2 (complement component 3 receptor 3 and 4 subunit) ITGB2 0.17 NM_000166 gap junction protein, beta 1, 32kDa GJB1 0.13 NM_000142 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) FGFR3 0.06 NM_000029 angiotensinogen (serpin peptidase inhibitor, clade A, member 8) AGT 0.05 BX405503 Alpha-fetoprotein 0.11 3) response to stress NM_052968 apolipoprotein A-V APOA5 0.16 NM_021871 fibrinogen alpha chain FGA 0.03 NM_020530 oncostatin M OSM 0.18 NM_014762 24-dehydrocholesterol reductase DHCR24 0.06 NM_006079 Cbp / p300-interacting transactivator, with Glu / Asp-rich carboxy-terminal domain, 2 CITED2 0.11 NM_005045 reelin RELN 0.13 NM_000301 plasminogen PLG 0.11 NM_000211 integrin, beta 2 (complement component 3 receptor 3 and 4 subunit) ITGB2 0.17 NM_000029 angiotensinogen (serpin peptidase inhibitor, clade A, member 8) AGT 0.05 NM_181738 peroxiredoxin 2 PRDX2 0.16 NM_014430 cell death-inducing DFFA-like effector b CIDEB 0.17 NM_006472 thioredoxin interacting protein TXNIP 0.05 NM_001786 cell division cycle 2, G1 to S and G2 to M CDC2 0.10 NM_001067 topoisomerase (DNA) II alpha 170kDa TOP2A 0.02 NM_172350 CD46 molecule, complement regulatory protein CD46 0.17 NM_013282 ubiquitin-like, containing PHD and RING finger domains, 1 UHRF1 0.07 NM_005432 X-ray repair complementing defective repair in Chinese hamster cells 3 XRCC3 0.11 NM_004591 chemokine (C-C motif) ligand 20 CCL20 0.16 NM_002758 mitogen-activated protein kinase kinase 6 MAP2K6 0.14 NM_002592 proliferating cell nuclear antigen PCNA 0.20 NM_002389 CD46 molecule, complement regulatory protein CD46 0.17 NM_002083 glutathione peroxidase 2 (gastrointestinal) GPX2 0.18 NM_001237 cyclin A2 CCNA2 0.14 NM_001071 thymidylate synthetase TYMS 0.17 NM_000847 glutathione S-transferase A3 GSTA3 0.07 NM_000716 complement component 4 binding protein, beta C4BPB 0.19 NM_000509 fibrinogen gamma chain FGG 0.04 NM_000457 hepatocyte nuclear factor 4, alpha HNF4A 0.20 NM_000313 protein S (alpha) PROS1 0.05 NM_000204 complement factor I CFI 0.03 NM_000185 serpin peptidase inhibitor, clade D (heparin cofactor), member 1 SERPIND1 0.08 NM_000130 coagulation factor V (proaccelerin, labile factor) F5 0.19 NM_000064 complement component 3 C3 0.19 NM_000042 apolipoprotein H (beta-2-glycoprotein I) APOH 0.07 BF591978 Apolipoprotein H (beta-2-glycoprotein I) 0.12 AF118092 predicted protein of HQ2061; Homo sapiens PRO2061 mRNA, complete cds. 0.03 4) cell cycle NM_014762 24-dehydrocholesterol reductase DHCR24 0.06 NM_006079 Cbp / p300-interacting transactivator, with Glu / Asp-rich carboxy-terminal domain, 2 CITED2 0.11 NM_006472 thioredoxin interacting protein TXNIP 0.05 NM_001786 cell division cycle 2, G1 to S and G2 to M CDC2 0.10 NM_013282 ubiquitin-like, containing PHD and RING finger domains, 1 UHRF1 0.07 NM_002758 mitogen-activated protein kinase kinase 6 MAP2K6 0.14 NM_002592 proliferating cell nuclear antigen PCNA 0.20 NM_001237 cyclin A2 CCNA2 0.14 NM_172164 nuclear autoantigenic sperm protein (histone-binding) NASP 0.16 NM_016343 centromere protein F, 350 / 400ka (mitosin) CENPF 0.05 NM_014333 cell adhesion molecule 1 CADM1 0.06 NM_007111 transcription factor Dp-1 TFDP1 0.15 NM_152722 hepatocyte cell adhesion molecule HEPACAM 0.06 NM_006403 neural precursor cell expressed, developmentally down-regulated 9 NEDD9 0.08 NM_003707 RuvB-like 1 (E. coli) RUVBL1 0.07 NM_001012271 baculoviral IAP repeat-containing 5 (survivin) BIRC5 0.13 NM_182908 dehydrogenase / reductase (SDR family) member 2 DHRS2 0.14 NM_153186 ankyrin repeat domain 15 ANKRD15 0.10 NM_031966 cyclin B1 CCNB1 0.13 NM_018571 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2 ALS2CR2 0.19 NM_018136 asp (abnormal spindle) homolog, microcephaly associated (Drosophila) ASPM 0.14 NM_015471 NSL1, MIND kinetochore complex component, homolog (S. cerevisiae) NSL1 0.19 NM_015261 non-SMC condensin II complex, subunit D3 NCAPD3 0.15 NM_006461 sperm associated antigen 5 SPAG5 0.16 NM_005915 minichromosome maintenance complex component 6 MCM6 0.17 NM_005030 polo-like kinase 1 (Drosophila) PLK1 0.13 NM_004701 cyclin B2 CCNB2 0.12 NM_002388 minichromosome maintenance complex component 3 MCM3 0.15 NM_002358 MAD2 mitotic arrest deficient-like 1 (yeast) MAD2L1 0.10 NM_001789 cell division cycle 25 homolog A (S. pombe) CDC25A 0.19 NM_001005414 Homo sapiens ZW10 interactor (ZWINT), transcript variant 4, mRNA [NM_001005414] 0.10 CR603982 MRNA; cDNA DKFZp313B1017 (from clone DKFZp313B1017) 0.11 5) regulation of biological quality NM_152722 hepatocyte cell adhesion molecule HEPACAM 0.06 NM_006403 neural precursor cell expressed, developmentally down-regulated 9 NEDD9 0.08 NM_003707 RuvB-like 1 (E. coli) RUVBL1 0.07 NM_021871 fibrinogen alpha chain FGA 0.03 NM_020530 oncostatin M OSM 0.18 NM_000301 plasminogen PLG 0.11 NM_000029 angiotensinogen (serpin peptidase inhibitor, clade A, member 8) AGT 0.05 NM_000716 complement component 4 binding protein, beta C4BPB 0.19 NM_000509 fibrinogen gamma chain FGG 0.04 NM_000457 hepatocyte nuclear factor 4, alpha HNF4A 0.20 NM_000313 protein S (alpha) PROS1 0.05 NM_000185 serpin peptidase inhibitor, clade D (heparin cofactor), member 1 SERPIND1 0.08 NM_000130 coagulation factor V (proaccelerin, labile factor) F5 0.19 NM_000042 apolipoprotein H (beta-2-glycoprotein I) APOH 0.07 BF591978 Apolipoprotein H (beta-2-glycoprotein I) 0.12 AF118092 predicted protein of HQ2061; Homo sapiens PRO2061 mRNA, complete cds. 0.03 U68494 Solute carrier family 30 (zinc transporter), member 1 0.19 NM_033502 transcriptional regulating factor 1 TRERF1 0.16 NM_000142 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) FGFR3 0.06 NM_172234 Homo sapiens interleukin 17 receptor B (IL17RB), transcript variant 2, mRNA [NM_172234] 0.15 NM_198252 gelsolin (amyloidosis, Finnish type) GSN 0.19 NM_015277 neural precursor cell expressed, developmentally down-regulated 4-like NEDD4L 0.09 NM_005143 haptoglobin HP 0.08 NM_004683 regucalcin (senescence marker protein-30) RGN 0.08 NM_004252 solute carrier family 9 (sodium / hydrogen exchanger), member 3 regulator 1 SLC9A3R1 0.14 NM_000039 apolipoprotein A-I APOA1 0.10 6) cell proliferation NM_021871 fibrinogen alpha chain FGA 0.03 NM_020530 oncostatin M OSM 0.18 NM_000301 plasminogen PLG 0.11 NM_000029 angiotensinogen (serpin peptidase inhibitor, clade A, member 8) AGT 0.05 NM_000509 fibrinogen gamma chain FGG 0.04 AF118092 predicted protein of HQ2061; Homo sapiens PRO2061 mRNA, complete cds. 0.03 NM_013282 ubiquitin-like, containing PHD and RING finger domains, 1 UHRF1 0.07 NM_002592 proliferating cell nuclear antigen PCNA 0.20 NM_172164 nuclear autoantigenic sperm protein (histone-binding) NASP 0.16 NM_016343 centromere protein F, 350 / 400ka (mitosin) CENPF 0.05 NM_014333 cell adhesion molecule 1 CADM1 0.06 NM_007111 transcription factor Dp-1 TFDP1 0.15 NM_005030 polo-like kinase 1 (Drosophila) PLK1 0.13 NM_001789 cell division cycle 25 homolog A (S. pombe) CDC25A 0.19 NM_057091 artemin ARTN 0.18 NM_020248 catenin, beta interacting protein 1 CTNNBIP1 0.17 NM_005631 smoothened homolog (Drosophila) SMO 0.08 NM_002729 hematopoietically expressed homeobox HHEX 0.11 NM_001360 7-dehydrocholesterol reductase DHCR7 0.19 NM_001005333 melanoma antigen family D, 1 MAGED1 0.14 NM_031942 cell division cycle associated 7 CDCA7 0.08 NM_001311 cysteine-rich protein 1 (intestinal) CRIP1 0.10 7) growth NM_021871 fibrinogen alpha chain FGA 0.03 NM_020530 oncostatin M OSM 0.18 NM_000301 plasminogen PLG 0.11 NM_000029 angiotensinogen (serpin peptidase inhibitor, clade A, member 8) AGT 0.05 NM_005631 smoothened homolog (Drosophila) SMO 0.08 NM_152722 hepatocyte cell adhesion molecule HEPACAM 0.06 NM_006403 neural precursor cell expressed, developmentally down-regulated 9 NEDD9 0.08 NM_003707 RuvB-like 1 (E. coli) RUVBL1 0.07 NM_000142 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) FGFR3 0.06 NM_172234 Homo sapiens interleukin 17 receptor B (IL17RB), transcript variant 2, mRNA [NM_172234] 0.15 NM_052968 apolipoprotein A-V APOA5 0.16 NM_173216 ST6 beta-galactosamide alpha-2,6-sialyltranferase 1 ST6GAL1 0.12 8) coagulation NM_021871 fibrinogen alpha chain FGA 0.03 NM_000301 plasminogen PLG 0.11 NM_000509 fibrinogen gamma chain FGG 0.04 AF118092 predicted protein of HQ2061; Homo sapiens PRO2061 mRNA, complete cds. 0.03 NM_000716 complement component 4 binding protein, beta C4BPB 0.19 NM_000457 hepatocyte nuclear factor 4, alpha HNF4A 0.20 NM_000313 protein S (alpha) PROS1 0.05 NM_000185 serpin peptidase inhibitor, clade D (heparin cofactor), member 1 SERPIND1 0.08 NM_000130 coagulation factor V (proaccelerin, labile factor) F5 0.19 NM_000042 apolipoprotein H (beta-2-glycoprotein I) APOH 0.07 BF591978 Apolipoprotein H (beta-2-glycoprotein I) 0.12 9) sterol metabolic process NM_001360 7-dehydrocholesterol reductase DHCR7 0.19 NM_033502 transcriptional regulating factor 1 TRERF1 0.16 NM_000039 apolipoprotein A-I APOA1 0.10 NM_014762 24-dehydrocholesterol reductase DHCR24 0.06 NM_006579 emopamil binding protein (sterol isomerase) EBP 0.16 NM_000859 3-hydroxy-3-methylglutaryl-Coenzyme A reductase HMGCR 0.16 NM_005502 ATP-binding cassette, sub-family A (ABC1), member 1 ABCA1 0.07 NM_004508 isopentenyl-diphosphate delta isomerase 1 IDI1 0.19 NM_000384 apolipoprotein B (including Ag (x) antigen) APOB 0.06 10) spindle checkpoint NM_016343 centromere protein F, 350 / 400ka (mitosin) CENPF 0.05 NM_001012271 baculoviral IAP repeat-containing 5 (survivin) BIRC5 0.13 NM_002358 MAD2 mitotic arrest deficient-like 1 (yeast) MAD2L1 0.10

< Example  3> Real time RT - PCR  dose

The degree of expression change of several genes overexpressed and underexpressed by the toxaphene of Example 2 was confirmed by real-time RT-PCR method.

Specifically, quantitative real-time RT-PCR was performed using My IQ Real-time PCR (Bio-rad, USA). Specifically, cDNA was synthesized by performing reverse transcription using an oligo dT primer and a Superscript kit (Omniscipt ™ kit, Qiagen, Co., USA). First, the primers for the target gene and endogenous control (RPLP0) used for PCR were added to the SYBR Green Master mix (Bio-rad, USA), and then PCR was selected. Primer optimization was performed. 0.2 µl of the cDNA, 3.8 µl of distilled water, 0.5 µl of the sense primer of Table 4, 0.5 µl of the antisense primer, and 5 µl of the Cyberrin I staining supermix (Bio-rad, USA) were added to the PCR tube, Step 1: 95 ° C. , 3 minutes; Step 2 (repeat 45): Step 2-1: 95 ° C., 10 seconds; Step 2-2: 55 to 65 ° C. 45 seconds; Step 3: 95 ° C., 1 minute; Step 4: 55 ° C., 1 minute; Step 5 (80 repetitions): The reaction was performed on a My IQ real-time PCR machine designed for program at 55 ° C., 10 seconds, followed by analysis using quantification software.

Cyberlin I staining is a staining method that binds to double-stranded DNA, which is used to quantify real-time RT-PCR products by increasing the fluorescence intensity as the double-stranded DNA is generated during the real-time RT-PCR process.

As a result, as shown in Table 5, the gene expression patterns of the six overexpression genes and the five low expression genes were confirmed to be very similar to those of the oligo microarray chip.

Primer sequence Registration Number Gene name PCR primer sequence (5 '-> 3') NM_001554 cysteine-rich, angiogenic inducer, 61 sense ATTGTAGAAAGGAAGCCTTGCTCAT (SEQ ID NO 1) Antisense TCCAATCGTGGCTGCATTAG (SEQ ID NO: 2) NM_003897 immediate early response 3 sense AGCCCTTTAATCTGACTTCGGAGC (SEQ ID NO 3) Antisense CAGGTACGCCTGGTGTTTCTTTGT (SEQ ID NO: 4) NM_000641 interleukin 11 sense TAAGGAGAGAGGCTTGCTTGGGAT (SEQ ID NO: 5) Antisense ACTTCAGTGATCCACTCGCTTCGT (SEQ ID NO: 6) NM_002305 lectin, galactoside-binding, soluble, 1 (galectin 1) sense TCGCCAGCAACCTGAATCTCAAAC (SEQ ID NO: 7) Antisense TTGTTGCTGTCTTTGCCCAGGTTC (SEQ ID NO: 8) NM_002203 integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) sense AACTCTTTGGATTTGCGTGTG (SEQ ID NO: 9) Antisense TGGCAGTCTCAGAATAGGCTTC (SEQ ID NO: 10) NM_021103 thymosin, beta 10 sense TTTCCTACCCCCGTCCTCTT (SEQ ID NO: 11) Antisense AGCTTGTGGCTCGTGTCCAT (SEQ ID NO: 12) NM_017915 chromosome 12 open reading frame 48 sense TATGCACCACCACCATCAGATCCT (SEQ ID NO: 13) Antisense CCCTGCAATGCTTGGGTTTGGTAT (SEQ ID NO: 14) NM_001809 centromere protein A sense TGCTGTCTGGACTTTGCTGTCTCT (SEQ ID NO: 15) Antisense TTTCAGGCCTTTGGAACGGTGTTG (SEQ ID NO: 16) NM_016343 centromere protein F, 350 / 400ka (mitosin) sense ACGGAAGGTACTGAGTTTGAGCCA (SEQ ID NO: 17) Antisense GAGTTGCCATGGTTGTTCTTCGCA (SEQ ID NO: 18) NM_001872 carboxypeptidase B2 (plasma) sense TCAGCATGCATTCATACTCCCAGC (SEQ ID NO: 19) Antisense TAGCACGAACTGCTTCACTGGCTA (SEQ ID NO: 20) NM_001948 dUTP pyrophosphatase sense CAGTTTGTGGAAGCACAGGCAAGA (SEQ ID NO: 21) Antisense ATGCTGGCTATGTCCCACTGAGTT (SEQ ID NO: 22)

Registration Number Gene name Toxaphene Real time PCR
(Relative magnification) cDNA Microarray
(Cy3 / Cy5 ratio) NM_001554 cysteine-rich, angiogenic inducer, 61 10.66 5.60 NM_003897 immediate early response 3 42.46 19.46 NM_000641 interleukin 11 14.26 9.69 NM_002305 lectin, galactoside-binding, soluble, 1 (galectin 1) 13.14 10.50 NM_002203 integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) 2.90 17.81 NM_021103 thymosin, beta 10 4.97 7.44 NM_017915 chromosome 12 open reading frame 48 0.09 0.18 NM_001809 centromere protein A 0.18 0.11 NM_016343 centromere protein F, 350 / 400ka (mitosin) 0.03 0.05 NM_001872 carboxypeptidase B2 (plasma) 0.01 0.02 NM_001948 dUTP pyrophosphatase 0.01 0.17

Thus, the genes selected by the experiment using the microarray chip of the present invention can be usefully used to confirm the exposure to toxaphene.

1 is a graph illustrating the cytotoxicity of toxaphene in human liver cancer cell lines.

Figure 2 is a diagram showing the results of analyzing the gene expression pattern in human liver cancer cell line treated with toxaphene using a microarray chip.

<110> Korea Instititue of Science and Technology <120> Biomarker for identification of exposure to toxaphene and the          method of identification using <130> 9P-02-19 <160> 22 <170> KopatentIn 1.71 <210> 1 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> CYR61 sense primer <400> 1 attgtagaaa ggaagccttg ctcat 25 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> CYR61 antisense primer <400> 2 tccaatcgtg gctgcattag 20 <210> 3 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> IER3 sense primer <400> 3 agccctttaa tctgacttcg gagc 24 <210> 4 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> IER3 antisense primer <400> 4 caggtacgcc tggtgtttct ttgt 24 <210> 5 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> IL11 sense primer <400> 5 taaggagaga ggcttgcttg ggat 24 <210> 6 <211> 24 <212> DNA <213> Artificial Sequence <220> IL223 antisense primer <400> 6 acttcagtga tccactcgct tcgt 24 <210> 7 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> LGALS1 sense primer <400> 7 tcgccagcaa cctgaatctc aaac 24 <210> 8 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> LGALS1 antisense primer <400> 8 ttgttgctgt ctttgcccag gttc 24 <210> 9 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> ITGA2 sense primer <400> 9 aactctttgg atttgcgtgt g 21 <210> 10 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> ITGA2 antisense primer <400> 10 tggcagtctc agaataggct tc 22 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> NM_021103 sense primer <400> 11 tttcctaccc ccgtcctctt 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> NM_021103 antisense primer <400> 12 agcttgtggc tcgtgtccat 20 <210> 13 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NM_017915 sense primer <400> 13 tatgcaccac caccatcaga tcct 24 <210> 14 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NM_017915 antisense primer <400> 14 ccctgcaatg cttgggtttg gtat 24 <210> 15 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NM_001809 sense primer <400> 15 tgctgtctgg actttgctgt ctct 24 <210> 16 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NM_001809 antisense primer <400> 16 tttcaggcct ttggaacggt gttg 24 <210> 17 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> CENPF sense primer <400> 17 acggaaggta ctgagtttga gcca 24 <210> 18 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> CENPF antisense primer <400> 18 gagttgccat ggttgttctt cgca 24 <210> 19 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NM_001872 sense primer <400> 19 tcagcatgca ttcatactcc cagc 24 <210> 20 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NM_001872 antisense primer <400> 20 tagcacgaac tgcttcactg gcta 24 <210> 21 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NM_001948 sense primer <400> 21 cagtttgtgg aagcacaggc aaga 24 <210> 22 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> NM_001948 antisense primer <400> 22 atgctggcta tgtcccactg agtt 24  

Claims (24)

Biomarker for confirming the exposure to toxaphene, characterized in that the expression changes by toxaphene exposure, including any one or more genes selected from the group: Genebank XM_939547 (zinc finger protein 697), Genebank U51869 [Human proto-oncogene Bcd orf1 and orf2 mRNA, complete cds. (U51869)], Genebank NR_002834 (dual specificity phosphatase 5 pseudogene), Genebank NM_207337 [antagonist of mitotic exit network 1 homolog (S. cerevisiae)], Genebank NM_203472 ( selenoprotein S), Genebank NM_203403 (chromosome 9 open reading frame 150), Genebank NM_203380 (acyl-CoA synthetase long-chain family member 5), Genebank NM_199330 [(homer) homolog 2 (Drosophila)], Genebank NM_182491 (zinc finger, AN1-type domain 2A), Genebank NM_181727 (spermatogenesis associated 12), Genebank NM_178234 (tumor suppressor candidate 3 ), Genebank NM_153020 (RNA binding motif protein 24), Genebank NM_152995 (nuclear transcription factor, X-box binding-like 1), Genebank NM_152673 (mucin 20, cell surface associated), gene registration number (G enebank) NM_145906 {Homo sapiens RIO kinase 3 (yeast) (RIOK3), transcript variant 2, mRNA [NM_145906]}, Genebank NM_145904 (high mobility group AT-hook 1), Genebank NM_144497 [A kinase (PRKA) anchor protein (gravin) 12], Genebank NM_080927 (discoidin, CUB and LCCL domain containing 2), Genebank NM_080655 (chromosome 9 open reading frame 30), Gene registration Genebank NM_080388 (S100 calcium binding protein A16), Genebank NM_052871 (hypothetical protein MGC4677), Genebank NM_033027 (AXIN1 up-regulated 1), Genebank NM_032717 (lung cancer metastasis-associated protein, Genebank NM_031459 (sestrin 2), Genebank NM_031412 [GABA (A) receptor-associated protein like 1)], Genebank NM_030627 (cytoplasmic polyadenylation) element binding protein 4), gene registration number (Geneba) nk) NM_024854 (hypothetical protein FLJ22028), Genebank NM_024713 (chromosome 15 open reading frame 29), Genebank NM_024580 (elongation factor Tu GTP binding domain containing 1), Genebank NM_024345 (WD repeat domain 32), Genebank NM_022818 (microtubule-associated protein 1 light chain 3 beta), Genebank NM_022157 (Ras-related GTP binding C), Genebank NM_021928 [ signal peptidase complex subunit 3 homolog (S. cerevisiae)], Genebank NM_021158 [tribbles homolog 3 (Drosophila)], Genebank NM_021103 (thymosin, beta 10), Genebank NM_020362 (chromosome 1 open reading frame 128), Genebank No. NM_019556 (motile sperm domain containing 1), Genebank No. NM_018590 (chondroitin sulfate GalNAcT-2), Genebank No. NM_018361 [1-acylglycerol-3-phosphate O-acyltransferase 5 ( lysophosphatidic acid acyltransferase, epsilon)], Genebank NM_017556 (filamin binding LIM protein 1), Genebank NM_016950 [sparc / osteonectin, cwcv and kazal-like domains proteoglycan (testican) 3], Gene registration Genebank NM_016470 (chromosome 20 open reading frame 111), Genebank NM_016131 (RAB10, member RAS oncogene family), Genebank NM_015167 (jumonji domain containing 6), Genebank (Genebank) NM_014685 (homocysteine -inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1), gene registration number (Genebank) NM_014624 (S100 calcium binding protein A6), gene registration number (Genebank) NM_014331 [solute carrier family 7, (cationic amino acid transporter) , y + system) member 11], Genebank NM_014059 (chromosome 13 open reading frame 15), Genebank NM_013320 (host cell factor C2), Genebank NM_013259 (transgelin 3), Genebank NM_012394 (prefoldin subunit 2), Genebank NM_012258 (hairy / enhancer-of-split related with YRPW motif 1), Genebank NM_012154 (eukaryotic translation initiation factor 2C, 2 ), Genebank NM_012110 (cysteine-rich hydrophobic domain 2), Genebank NG_006644 (heat shock 105kDa / 110kDa protein 1), Genebank NM_005843 [signal transducing adapter molecule (SH3 domain) and ITAM motif) 2], Genebank NM_005746 (pre-B-cell colony enhancing factor 1), Genebank NM_005347 [heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)], Genebank (Genebank) ) NM_005228 [epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)], gene registration number (Genebank) NM_005110 (glutamine-fructose-6-phosphate transaminase 2), gene registration number (Genebank) NM_005018 (programmed cell death 1), Genebank NM_004972 [Janus kinase 2 (a protein tyrosine kinase)], Genebank NM_004926 (zinc finger protein 36, C3H type-like 1), gene registration number (Genebank) NM_004925 [aquaporin 3 (Gill blood group)], gene registration number (Genebank) NM_004760 (serine / threonine kinase 17a), gene registration number (Genebank) NM_004666 (vanin 1), gene registration number (Genebank) NM_004417 (dual specificity phosphatase 1), Genebank NM_004398 [DEAD (Asp-Glu-Ala-Asp ) box polypeptide 10], Genebank NM_004171 [solute carrier family 1 (glial high affinity glutamate transporter), member 2], Genebank NM_004073 [olo-like kinase 3 (Drosophila)], Gene registration Genebank NM_004024 (activating transcription factor 3), Genebank NM_003979 (G protein-coupled receptor, family C, group 5, member A), Genebank NM_003937 [kynureninase (L-kynurenine hydrolase), Genebank NM_003897 (immediate early response 3), Genebank NM_003873 (neuropilin 1), Genebank NM_003806 [harakiri, BCL2 interacting protein (contains only BH3 domain)] , Genebank NM_003608 (G protein-coupled receptor 65), Genebank NM_003407 [zinc finger protein 36, C3H type, homolog (mouse)], Genebank NM_003388 (CAP-GLY domain containing linker protein 2), Genebank ) NM_003254 (TIMP metallopeptidase inhibitor 1), Genebank NM_003122 (serine peptidase inhibitor, Kazal type 1), Genebank NM_003113 (SP100 nuclear antigen), Genebank NM_002436 (membrane protein, palmitoylated 1, 55 kDa), Genebank NM_002421 [matrix metallopeptidase 1 (interstitial collagenase)], Genebank NM_002394 [solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2], Genebank NM_002309 [leukemia inhibitory factor (cholinergic differentiation factor)], Genebank NM_002305 [lectin, galactoside-binding, soluble, 1 (galectin 1)], Genebank NM_002288 (leukocyte -associated immunoglobulin-like receptor 2), Genebank number NM_002276 (keratin 19), Genebank number NM_002224 (inositol 1,4,5-triphosphate receptor, type 3), Genebank number (Genebank) NM_002 203 [integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)], gene registration number (Genebank) NM_002143 (hippocalcin), gene registration number (Genebank) NM_002131 (high mobility group AT-hook 1), gene registration Number (Genebank) NM_002061 (glutamate-cysteine ligase, modifier subunit), gene registration number (Genebank) NM_002056 (glutamine-fructose-6-phosphate transaminase 1), gene registration number (Genebank) NM_002032 (ferritin, heavy polypeptide 1) Genebank NM_001902 [cystathionase (cystathionine gamma-lyase)], Genebank NM_001731 (B-cell translocation gene 1, anti-proliferative), Genebank NM_001730 [Kruppel-like factor 5 ( intestinal)], Genebank NM_001614 (actin, gamma 1), Genebank NM_001554 (cysteine-rich, angiogenic inducer, 61), Genebank NM_001421 [E74-like factor 4 ( ets domain transcription factor], Genebank NM_001013398 (insulin-like growth factor binding protein 3), Genebank NM_000641 (interleukin 11), Genebank NM_000602 [serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1], gene registration number Genebank NM_000584 (interleukin 8), Genebank NM_000574 [CD55 molecule, decay accelerating factor for complement (Cromer blood group)], Genebank NM_000433 [neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease) , autosomal 2)], Genebank NM_000259 [myosin VA (heavy chain 12, myoxin)], Genebank NM_000214 [jagged 1 (Alagille syndrome)], Genebank NM_000202 [iduronate 2-sulfatase (Hunter syndrome)], Genebank D55639 [Kynureninase (L-kynurenine hydrolase)], Genebank BG001037 (Thioredoxin reductase 1), Genebank BC070200 (hypothetical LOC541471) , Genes, etc. Number (Genebank) BC030702 (microcephaly, primary autosomal recessive 1), gene registration number (Genebank) BC005130 (hypothetical protein MGC11082), Genebank AF180519 [GABA (A) receptors associated protein like 3], gene registration number ( Genebank) AB007870 (nucleoporin like 1), Genebank XM_940101 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 11], Genebank XM_938617 {PREDICTED: Homo sapiens hypothetical protein LOC649542 (LOC649542), mRNA [XM_938617]}, Genebank XM_936688 {PREDICTED: Homo sapiens similar to Ceruloplasmin precursor (Ferroxidase) (LOC441368), mRNA [XM_926222]}, Gene accession number (Genebank) XM_935655 [R nucleotide exchange factor (GEF) 5, Genebank XM_372002 [amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2 pseudogene], Genebank U68494 [Solute carrier family 30 (zinc transporte) r), member 1], Genebank NR_002932 (glutathione S-transferase M1 pseudogene), Genebank NR_002187 (hypothetical protein LOC286016), Genebank NM_203481 (hypothetical LOC403340), gene Genebank NM_201523 (kinesin light chain 4), Genebank NM_199337 (similar to RIKEN cDNA 1810059G22), Genebank NM_199327 [sprouty homolog 1, antagonist of FGF signaling (Drosophila)] Genebank NM_198504 (progestin and adipoQ receptor family member IX), Genebank NM_198252 [gelsolin (amyloidosis, Finnish type)], Genebank NM_183075 (cytochrome P450, family 2, subfamily U, polypeptide 1), genebank NM_182908 [dehydrogenase / reductase (SDR family) member 2], genebank (Genebank) NM_182760 (sulfatase modifying factor 1), genebank NM_181738 (peroxiredoxin 2), gene Registration number Genebank NM_177550 [solute carrier family 13 (sodium-dependent citrate transporter), member 5], Genebank NM_176787 (phosphatidylinositol glycan anchor biosynthesis, class N), Genebank NM_175887 (proline rich 15 ), Gene registration number (Genebank) NM_173500 (tau tubulin kinase 2), gene registration number (Genebank) NM_173216 (ST6 beta-galactosamide alpha-2,6-sialyltranferase 1), gene registration number (Genebank) NM_172350 (CD46 molecule, complement regulatory protein), Genebank NM_172234 {Homo sapiens interleukin 17 receptor B (IL17RB), transcript variant 2, mRNA [NM_172234]}, Genebank NM_172164 [nuclear autoantigenic sperm protein (histone-binding) ], Genebank NM_153631 (homeobox A3), Genebank NM_153482 {Homo sapiens interleukin 17 receptor E (IL17RE), transcript variant 4, mRNA [NM_153482]}, Genebank NM_153344 { Homo sapiens chromosome 6 op en reading frame 141 (C6orf141), mRNA [NM_153344], Genebank NM_153186 (ankyrin repeat domain 15), Genebank NM_152764 (chromosome 16 open reading frame 73), Genebank (Genebank) NM_152722 (hepatocyte cell adhesion molecule), Genebank NM_152718 (von Willebrand factor C and EGF domains), Genebank NM_152379 (chromosome 1 open reading frame 131), Genebank NM_152308 (chromosome 16 open reading frame 75), Genebank NM_152299 (non-SMC condensin II complex, subunit H2), Genebank NM_148979 (cathepsin H), Genebank NM_145740 (glutathione S-transferase A1), Genebank NM_144966 (FRAS1 related extracellular matrix 1), Genebank NM_144595 (SLAIN motif family, member 1), Genebank NM_138730 (high mobility group nucleosomal binding domain 3) , Gene registration Genebank NM_138476 (magnesium-dependent phosphatase 1), Genebank NM_130806 (relaxin / insulin-like family peptide receptor 2), Genebank NM_058186 (family with sequence similarity 3, member B), Genebank (Genebank) NM_057091 (artemin), Genebank (Genebank) NM_054113 (calcium and integrin binding family member 3), Genebank (Genebank) NM_052968 (apolipoprotein AV), Genebank (Genebank) NM_033515 (Rho GTPase activating protein 18), Genebank NM_033502 (transcriptional regulating factor 1), Genebank NM_033380 [collagen, type IV, alpha 5 (Alport syndrome)], Genebank NM_033133 (2 ' , 3'-cyclic nucleotide 3 'phosphodiesterase, Genebank NM_031966 (cyclin B1), Genebank NM_031942 (cell division cycle associated 7), Genebank NM_031311 (carboxypeptidase, vitellogenic- like), heredity Genebank NM_030919 (family with sequence similarity 83, member D), Genebank NM_024743 (UDP glucuronosyltransferase 2 family, polypeptide A3), Genebank NM_024709 (chromosome 1 open reading frame 115), Genebank NM_024103 [solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 23], Genebank number NM_021871 (fibrinogen alpha chain), gene number (Genebank) NM_021139 (UDP glucuronosyltransferase 2 family, polypeptide B4), gene number (Genebank) NM_021069 (sorbin and SH3 domain containing 2), Genebank NM_020995 (haptoglobin-related protein), Genebank NM_020548 [diazepam binding inhibitor (GABA receptor modulator, acyl-Coenzyme A binding protein)], Genebank NM_020530 (oncostatin M), Genebank NM_020248 (catenin, beta interacting protein 1), Genebank NM_019101 (apolipoprotein M), Genebank NM_018663 (peroxisomal membrane protein 2, 22kDa), gene Genebank NM_018647 (tumor necrosis factor receptor superfamily, member 19), Genebank NM_018571 [amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2], Gene accession number (Genebank) bank) NM_018410 (hypothetical protein DKFZp762E1312), Genebank NM_018136 [asp (abnormal spindle) homolog, microcephaly associated (Drosophila)], Genebank NM_017915 (chromosome 12 open reading frame 48), gene registration number (Genebank) NM_017899 (tescalcin), Genebank NM_017893 [sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4G], Genebank NM_017855 (odontogenic , ameloblast asssociated, Genebank NM_017779 (DEP domain containing 1), Genebank NM_017770 [elongation of very long chain fatty acids (FEN1 / Elo2, SUR4 / Elo3, yeast) -like 2], Genebank No. NM_017763 (ring finger protein 43), Genebank No. NM_017410 (homeobox C13), Genebank No. NM_016824 [adducin 3 (gamma)], Genebank No. NM_016619 (placenta) -specific 8), gene registration number ( Genebank) NM_016618 (lysine-rich coiled-coil 1), Genebank NM_016343 [centromere protein F, 350 / 400ka (mitosin)], Genebank NM_016297 (prenylcysteine oxidase 1), Gene Registration Number ( Genebank) NM_016256 (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase), Gene Registration Number (Genebank) NM_015974 (crystallin, lambda 1), Gene Registration Number (Genebank) NM_015917 (glutathione S-transferase kappa 1), Gene Registration Genebank NM_015471 [NSL1, MIND kinetochore complex component, homolog (S. cerevisiae)], Genebank NM_015385 (sorbin and SH3 domain containing 1), Genebank NM_015277 (neural precursor cell expressed, developmentally down-regulated 4-like), Genebank NM_015261 ( non-SMC condensin II complex, subunit D3), Genebank NM_015071 (Rho GTPase activating protein 26), Genebank NM_015008 (transmembrane and coiled-coil domain family 1), Genebank (Genebank) NM_014762 (24-dehydrocholesterol reductase), Genebank (Genebank) NM_014430 (cell death-inducing DFFA-like effector b), Gene Registration Number (Genebank) NM_014333 (cell adhesion molecule 1), Gene Registration Number (Genebank) NM_014298 {quinolinate phosphoribosyltransferase [nicotinate-nucleotide pyrophosphorylase (carboxylating)], Genebank NM_014176 [ubiquitin-conjugating enzyme E2T (putative)], Genebank NM_014109 (ATPase family, AAA domain containing 2), Genebank NM_013282 (ubiquitin-like, containing PHD and RING finger domains, 1), Genebank NM_012484 [hyaluronan-mediated motility receptor (RHAMM)], Genebank NM_012288 (translocation associated membrane protein 2), Genebank NM_007256 (solute carrier organic anion transporter family, member 2B1), Genebank NM_007111 (transcription factor Dp-1), Genebank NM_006876 (UDP-GlcNAc : betaGal beta-1,3-N-acetylglucosaminyltransferase 1), Genebank NM_006863 [leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 1], Genebank NM_006821 (acyl- CoA thioesterase 2), Genebank NM_006744 (retinol binding protein 4, plasma), Genebank NM_006579 [emopamil binding protein (sterol isomerase)], Genebank NM_006546 (insulin-like growth factor 2 mRNA bindi ng protein 1), Genebank NM_006472 (thioredoxin interacting protein), Genebank NM_006461 (sperm associated antigen 5), Genebank NM_006403 (neural precursor cell expressed, developmentally down-regulated 9 ), Genebank NM_006079 (Cbp / p300-interacting transactivator, with Glu / Asp-rich carboxy-terminal domain, 2), Genebank NM_006055 [LanC lantibiotic synthetase component C-like 1 (bacterial) ], Genebank NM_005940 [matrix metallopeptidase 11 (stromelysin 3)], Genebank NM_005915 (minichromosome maintenance complex component 6), Genebank NM_005767 (purinergic receptor P2Y, G-protein coupled) , 5), Genebank NM_005733 (kinesin family member 20A), Genebank NM_005631 [smoothened homolog (Drosophila)], Genebank NM_005573 (lamin B1), Genebank (Genebank) ) NM_005567 (lectin, galactoside-binding, soluble, 3 binding protein), Genebank NM_005566 (lactate dehydrogenase A), Genebank NM_005502 [ATP-binding cassette, sub-family A (ABC1), member 1], Genebank NM_005432 (X-ray repair complementing defective repair in Chinese hamster cells 3), Genebank NM_005271 (glutamate dehydrogenase 1), Genebank NM_005165 (aldolase C, fructose) -bisphosphate), Gene Registration Number (Genebank) NM_005143 (haptoglobin), Gene Registration Number (Genebank) NM_005063 [stearoyl-CoA desaturase (delta-9-desaturase)], Gene Registration Number (Genebank) NM_005045 (reelin), Gene Registration Number (Genebank) NM_005030 [polo-like kinase 1 (Drosophila)], gene accession number (Genebank) NM_005021 (ectonucleotide pyrophosphatase / phosphodiesterase 3), gene accession number (Genebank) NM_004884 (putative neuronal cell adhesion molecule), gene registration number (Genebank) ) NM_004772 (chromosome 5 open reading frame 13), Genebank NM_004701 (cyclin B2), Genebank NM_004683 [regucalcin (senescence marker protein-30)], Genebank NM_004640 (HLA-B associated transcript 1), Genebank NM_004591 [chemokine (CC motif) ligand 20], Genebank NM_004508 (isopentenyl-diphosphate delta isomerase 1), Genebank NM_004428 (ephrin-A1), Gene Genebank NM_004252 [solute carrier family 9 (sodium / hydrogen exchanger), member 3 regulator 1], Genebank NM_004164 (retinol binding protein 2, cellular), Genebank NM_004107 (Fc fragment of IgG, receptor, transporter, alpha), Genebank NM_004086 [coagulation factor C homolog, cochlin (Limulus polyphemus)], Genebank NM_003713 (phosphatidic acid phosphatase type 2B), Genebank (Genebank) ) NM_003707 [RuvB-like 1 (E. coli)], Genebank NM_003667 (leucine-rich repeat-containing G protein-coupled receptor 5), Genebank NM_003634 [nipsnap homolog 1 (C. elegans)], Genebank (Genebank) NM_003559 (phosphatidylinositol-4-phosphate 5-kinase, type II, beta), Genebank NM_003488 [A kinase (PRKA) anchor protein 1], Genebank NM_003483 (high mobility group AT-hook 2 ), Genebank NM_003270 (tetraspanin 6), Genebank NM_003243 (transforming growth factor, beta receptor III), Genebank NM_003216 (thyrotrophic embryonic factor), Genebank (Genebank) NM_003118 [secreted protein, acidic, cysteine-rich (osteonectin)], gene registration number (Genebank) NM_003104 (sorbitol dehydrogenase), gene registration number (Genebank) NM_003022 (SH3 domain binding glutamic acid-rich protein like), gene registration number ( Genebank) NM_002998 (syndecan 2), gene registration number (G enebank NM_002959 (sortilin 1), Genebank NM_002860 (aldehyde dehydrogenase 18 family, member A1), Genebank NM_002758 (mitogen-activated protein kinase kinase 6), Genebank NM_002729 (Genebank) hematopoietically expressed homeobox, Genebank NM_002630 [progastricsin (pepsinogen C)], Genebank NM_002611 (pyruvate dehydrogenase kinase, isozyme 2), Genebank NM_002592 (proliferating cell nuclear antigen), Genebank No. NM_002567 (phosphatidylethanolamine binding protein 1), Genebank No. NM_002508 (nidogen 1), Genebank No. NM_002413 (microsomal glutathione S-transferase 2), Genebank No. NM_002389 (Genebank) CD46 molecule, complement regulatory protein, Genebank NM_002388 (minichromosome maintenance complex component 3), Genebank NM_002358 [MAD2 mitotic arrest deficient- like 1 (yeast)], Genebank NM_002340 [lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase)], Genebank NM_002334 (low density lipoprotein receptor-related protein 4), Gene accession number (Genebank) NM_002317 (lysyl oxidase), Genebank (Genebank) NM_002083 [glutathione peroxidase 2 (gastrointestinal)], Genebank (Genebank) NM_001948 (dUTP pyrophosphatase), Genebank (Menebank) NM_001914 [cytochrome b5 type A microsomal)], Genebank NM_001872 [carboxypeptidase B2 (plasma)], Genebank NM_001815 (carcinoembryonic antigen-related cell adhesion molecule 3), Genebank NM_001809 (centromere protein A), Genebank NM_001789 [cell division cycle 25 homolog A (S. pombe), Genebank NM_001786 (cell division cycle 2, G1 to S and G2 to M), Genebank NM_001756 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6], Genebank NM_001712 [carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)], Genebank NM_001461 (flavin containing monooxygenase 5), Genebank NM_001444 [fatty acid binding protein 5 (psoriasis-associated)], Genebank NM_001412 (eukaryotic translation initiation factor 1A, X-linked), Genebank NM_001360 (7-dehydrocholesterol reductase), Genebank NM_001359 ( 2,4-dienoyl CoA reductase 1, mitochondrial), Genebank NM_001311 [cysteine-rich protein 1 (intestinal)], Genebank NM_001237 (cyclin A2), Genebank NM_001182 (Genebank) aldehyde dehydrogenase 7 family, member A1), Genebank NM_001150 [alanyl (membrane) aminopeptidase N, aminopeptidase M, microsomal aminopeptidase, CD13, p150)], Genebank NM_001134 (alpha-fetoprotein), Genebank (Genebank) ) NM_001116 (adenylate cyclase 9), Genebank (Genebank) NM_001077 (UDP glucuronosyltransferase 2 family, polypeptide B17), Genebank (Genebank) NM_001075 (UDP glucuronosyltransferase 2 family, polypeptide B10), Gene registration number (Genebank) NM_001074 UDP glucuronosyltransferase 2 family, polypeptide B7), Genebank (Genebank) NM_001073 (UDP glucuronosyltransferase 2 family, polypeptide B11), Gene accession (Genebank) NM_001072 (UDP glucuronosyltransferase 1 family, polypeptide A6), Gene Registration Number (Genebank1) NM_ (thymidylate synthetase), Genebank NM_001067 (topoisomerase (DNA) II alpha 170kDa), Genebank NM_001040152 (paternally expressed 10) Genebank NM_001024074 (histamine N-methyltransferase), Genebank NM_001017395 (transmembrane and coiled-coil domain family 1), Genebank NM_001012271 [baculoviral IAP repeat-containing 5 (survivin)], Genebank NM_001010983 (glycosyltransferase 8 domain containing 1), Genebank NM_001005414 {Homo sapiens ZW10 interactor (ZWINT), transcript variant 4, mRNA [NM_001005414]}, Genebank NM_001005333 (melanoma antigen family D, 1), Genebank NM_001004320 (hypothetical protein LOC392636), Genebank NM_001003845 (Sp5 transcription factor), Genebank NM_001001290 (solute carrier family 2 (facilitated glucose transporter) , member 9], Genebank NM_000953 {prostaglandin D2 receptor (DP)}, Genebank NM_000859 (3-hydroxy-3-methylglutaryl-Coenzyme A reductase), Gene Registration Number (Genebank) NM_000851 (glutathione S-transferase M5), Genebank NM_000847 (glutathione S-transferase A3), Gene Registration Number (Genebank) NM_000791 (dihydrofolate reductase), Gene Registration Number (Genebank) NM_000790 [dopa decarboxylase (dopa decarboxylase (Genebank) aromatic L-amino acid decarboxylase)], Genebank NM_000784 (cytochrome P450, family 27, subfamily A, polypeptide 1), Genebank NM_000716 (complement component 4 binding protein, beta), Gene accession number (Genebank) NM_000689 (aldehyde dehydrogenase 1 family, member A1), Genebank NM_000672 [alcohol dehydrogenase 6 (class V)], Genebank NM_000671 [alcohol dehydrogenase 5 (class III), chi polypeptide] , Genebank NM_000638 (vitronectin), Genebank NM_000624 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5], Genebank NM_000509 (fibrinogen gamma chain ), U Genebank NM_000495 [collagen, type IV, alpha 5 (Alport syndrome)], Genebank (Genebank) NM_000483 (apolipoprotein C-II), Genebank (Menebank) NM_000457 (hepatocyte nuclear factor 4, alpha) , Genebank NM_000384 [apolipoprotein B (including Ag (x) antigen)], Genebank NM_000371 [transthyretin (prealbumin, amyloidosis type I)], Genebank NM_000365 (triosephosphate isomerase 1), Genebank NM_000354 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 7], Genebank NM_000313 [protein S (alpha)], gene registry number (Genebank) ) NM_000301 (plasminogen), Gene Registration Number (Genebank) NM_000277 (phenylalanine hydroxylase), Gene Registration Number (Genebank) NM_000253 (microsomal triglyceride transfer protein), Gene Registration Number (Genebank) NM_000211 [integrin, beta 2 (complement component 3 receptor 3) and 4 subunit)], gene Genebank NM_000204 (complement factor I), Genebank NM_000185 [serpin peptidase inhibitor, clade D (heparin cofactor), member 1], Genebank NM_000166 (gap junction protein, beta 1, 32 kDa), Genebank NM_000142 [fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)], Genebank NM_000130 [coagulation factor V (proaccelerin, labile factor)], Genebank NM_000064 (complement component 3), gene registration number (Genebank) NM_000042 [apolipoprotein H (beta-2-glycoprotein I)], gene registration number (Genebank) NM_000040 (apolipoprotein C-III), gene registration number (Genebank) NM_000039 (apolipoprotein AI) ), Genebank NM_000029 [angiotensinogen (serpin peptidase inhibitor, clade A, member 8)], Genebank NM_000014 (alpha-2-macroglobulin), Genebank M10036 (triosephosphate isomerase 1 ), Gene Registration No. (Genebank) CR627122 [MRNA; cDNA DKFZp779M2422 (from clone DKFZp779M2422)], Genebank CR625412 [acidic (leucine-rich) nuclear phosphoprotein 32 family, member A], Genebank CR624291 (CDNA: FLJ22515 fis, clone HRC12122, highly similar to AF052101 Homo sapiens clone 23872 mRNA sequence), Genebank CR605719 [Full-length cDNA clone CS0DK002YG10 of HeLa cells Cot 25-normalized of Homo sapiens (human)], Genebank CR603982 [MRNA; cDNA DKFZp313B1017 (from clone DKFZp313B1017)], Genebank number BX405503 (Alpha-fetoprotein), Gene accession number (Genebank) BU783246 (in01c10.y1 Human insulinoma Homo sapiens cDNA clone IMAGE: 6123258 5 'similar to SWMANAD11766_ ALCOHOL DEHYDROGENASE CLASS III CHI CHAIN;, mRNA sequence.), Genebank BM928667 (Transcribed locus), Genebank BG591978 [Apolipoprotein H (beta-2-glycoprotein I)], Genebank (Genebank) ) BC067900 (hypothetical LOC149837), Genebank BC064969 (Acidic (leucine-rich) nuclear phosphoprotein 32 family, member A), Genebank BC050733 [ATP-binding cassette, sub-family C (CFTR / MRP), member 6], Genebank BC050292 (MGC44478), Genebank BC039065 [alcohol dehydrogenase 6 (class V)], Genebank BC027988 (hypothetical protein LOC253842), gene Registration Number (Genebank) BC006267 (asparaginase like 1), Genebank AK123483 (CDNA FLJ41489 fis, clone BRTHA2004582), Genebank AK095855 (CDNA clone IMAGE: 4513453), Genebank AF132203 (PRO1933), Genebank AF118092 (Genebank) predicted protein of HQ2061; Homo sapiens PRO2061 mRNA, complete cds.), Genebank AF007149 (hypothetical protein LOC257407). The biomarker of claim 1, wherein the expression of the following genes is increased by exposure to toxaphene: Genebank XM_939547 (zinc finger protein 697), Genebank U51869 [Human proto-oncogene Bcd orf1 and orf2 mRNA, complete cds. (U51869)], Genebank NR_002834 (dual specificity phosphatase 5 pseudogene), Genebank NM_207337 [antagonist of mitotic exit network 1 homolog (S. cerevisiae)], Genebank NM_203472 ( selenoprotein S), Genebank NM_203403 (chromosome 9 open reading frame 150), Genebank NM_203380 (acyl-CoA synthetase long-chain family member 5), Genebank NM_199330 [(homer) homolog 2 (Drosophila)], Genebank NM_182491 (zinc finger, AN1-type domain 2A), Genebank NM_181727 (spermatogenesis associated 12), Genebank NM_178234 (tumor suppressor candidate 3 ), Genebank NM_153020 (RNA binding motif protein 24), Genebank NM_152995 (nuclear transcription factor, X-box binding-like 1), Genebank NM_152673 (mucin 20, cell surface associated), gene registration number (G enebank) NM_145906 {Homo sapiens RIO kinase 3 (yeast) (RIOK3), transcript variant 2, mRNA [NM_145906]}, Genebank NM_145904 (high mobility group AT-hook 1), Genebank NM_144497 [A kinase (PRKA) anchor protein (gravin) 12], Genebank NM_080927 (discoidin, CUB and LCCL domain containing 2), Genebank NM_080655 (chromosome 9 open reading frame 30), Gene registration Genebank NM_080388 (S100 calcium binding protein A16), Genebank NM_052871 (hypothetical protein MGC4677), Genebank NM_033027 (AXIN1 up-regulated 1), Genebank NM_032717 (lung cancer metastasis-associated protein, Genebank NM_031459 (sestrin 2), Genebank NM_031412 [GABA (A) receptor-associated protein like 1], Genebank NM_030627 (cytoplasmic polyadenylation element binding protein 4), Gene Registration Number (Geneban k) NM_024854 (hypothetical protein FLJ22028), Genebank NM_024713 (chromosome 15 open reading frame 29), Genebank NM_024580 (elongation factor Tu GTP binding domain containing 1), Genebank NM_024345 (WD repeat domain 32), Genebank NM_022818 (microtubule-associated protein 1 light chain 3 beta), Genebank NM_022157 (Ras-related GTP binding C), Genebank NM_021928 [ signal peptidase complex subunit 3 homolog (S. cerevisiae)], Genebank NM_021158 [tribbles homolog 3 (Drosophila)], Genebank NM_021103 (thymosin, beta 10), Genebank NM_020362 (chromosome 1 open reading frame 128), Genebank No. NM_019556 (motile sperm domain containing 1), Genebank No. NM_018590 (chondroitin sulfate GalNAcT-2), Genebank No. NM_018361 [1-acylglycerol-3-phosphate O-acyltransferase 5 ( lysophosphatidic acid acyltransferase, epsilon)], Genebank NM_017556 (filamin binding LIM protein 1), Genebank NM_016950 [sparc / osteonectin, cwcv and kazal-like domains proteoglycan (testican) 3], Gene registration Genebank NM_016470 (chromosome 20 open reading frame 111), Genebank NM_016131 (RAB10, member RAS oncogene family), Genebank NM_015167 (jumonji domain containing 6), Genebank (Genebank) NM_014685 (homocysteine- inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1), Genebank NM_014624 (S100 calcium binding protein A6), Genebank NM_014331 [solute carrier family 7, (cationic amino acid transporter, y + system) member 11], Genebank NM_014059 (chromosome 13 open reading frame 15), Genebank NM_013320 (host cell factor C2), Genebank NM_013259 (transgelin 3), Gene Genebank NM_012394 (prefoldin subunit 2), Genebank NM_012258 (hairy / enhancer-of-split related with YRPW motif 1), Genebank NM_012154 (eukaryotic translation initiation factor 2C, 2) , Genebank NM_012110 (cysteine-rich hydrophobic domain 2), Genebank NM_006644 (heat shock 105kDa / 110kDa protein 1), Genebank NM_005843 [signal transducing adaptor molecule (SH3 domain and ITAM motif) 2 ], Genebank NM_005746 (pre-B-cell colony enhancing factor 1), Genebank NM_005347 [heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)], Genebank (Genebank) NM_005228 [epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)], gene registration number (Genebank) NM_005110 (glutamine-fructose-6-phosphate transaminase 2), gene registration number (Genebank) NM_005018 (programmed cell death 1), Genebank NM_004972 [Janus kinase 2 (a protein tyrosine kinase)], Genebank NM_004926 (zinc finger protein 36, C3H type-like 1), gene registration number ( Genebank) NM_004925 [aquaporin 3 (Gill blood group)], Genebank NM_004760 (serine / threonine kinase 17a), Genebank NM_004666 (vanin 1), Genebank NM_004417 (dual specificity phosphatase 1), Genebank NM_004398 [DEAD (Asp-Glu-Ala-Asp ) box polypeptide 10], Genebank NM_004171 [solute carrier family 1 (glial high affinity glutamate transporter), member 2], Genebank NM_004073 [olo-like kinase 3 (Drosophila)], Gene registration Genebank NM_004024 (activating transcription factor 3), Genebank NM_003979 (G protein-coupled receptor, family C, group 5, member A), Genebank NM_003937 [kynureninase (L-kynurenine hydrolase) )], Genebank NM_003897 (immediate early response 3), Genebank NM_003873 (neuropilin 1), Genebank NM_003806 [harakiri, BCL2 interacting protein (contains only BH3 domain)], Genebank NM_003608 (G protein-coupled receptor 65), Genebank NM_003407 [zinc finger protein 36, C3H type, homolog (mouse)], Genebank NM_003388 (CAP-GLY domain containing linker protein 2), Genebank NM_003254 (TIMP metallopeptidase inhibitor 1), Genebank (Genebank) NM_003122 (serine peptidase inhibitor, Kazal type 1), Gene Registration Number (Genebank) NM_003113 (SP100 nuclear antigen), Gene Registration Number (Genebank) NM_002436 (membrane protein, palmitoylated 1, 55 kDa), Genebank NM_002421 [matrix metallopeptidase 1 (interstitial collagenase)], Genebank NM_002394 [solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2], gene Genebank NM_002309 [leukemia inhibitory factor (cholinergic differentiation factor)], Genebank NM_002305 [lectin, galactoside-binding, soluble, 1 (galectin 1)], Genebank NM_002288 (leukocyte- associated immunoglobulin-like receptor 2), genebank NM_002276 (keratin 19), genebank NM_002224 (inositol 1,4,5-triphosphate receptor, type 3), genebank NM_0022 03 [integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)], gene registration number (Genebank) NM_002143 (hippocalcin), gene registration number (Genebank) NM_002131 (high mobility group AT-hook 1), gene registration Number (Genebank) NM_002061 (glutamate-cysteine ligase, modifier subunit), gene registration number (Genebank) NM_002056 (glutamine-fructose-6-phosphate transaminase 1), gene registration number (Genebank) NM_002032 (ferritin, heavy polypeptide 1) Genebank NM_001902 [cystathionase (cystathionine gamma-lyase)], Genebank NM_001731 (B-cell translocation gene 1, anti-proliferative), Genebank NM_001730 [Kruppel-like factor 5 ( intestinal)], Genebank NM_001614 (actin, gamma 1), Genebank NM_001554 (cysteine-rich, angiogenic inducer, 61), Genebank NM_001421 [E74-like factor 4 ( ets domain transcription factor], Genebank NM_001013398 (insulin-like growth factor binding protein 3), Genebank NM_000641 (interleukin 11), Genebank NM_000602 [serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1], gene registration number Genebank NM_000584 (interleukin 8), Genebank NM_000574 [CD55 molecule, decay accelerating factor for complement (Cromer blood group)], Genebank NM_000433 [neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease) , autosomal 2)], Genebank NM_000259 [myosin VA (heavy chain 12, myoxin)], Genebank NM_000214 [jagged 1 (Alagille syndrome)], Genebank NM_000202 [iduronate 2-sulfatase (Hunter syndrome)], Genebank D55639 [Kynureninase (L-kynurenine hydrolase)], Genebank BG001037 (Thioredoxin reductase 1), Genebank BC070200 (hypothetical LOC541471) , Gene registration Number (Genebank) BC030702 (microcephaly, primary autosomal recessive 1), gene registration number (Genebank) BC005130 (hypothetical protein MGC11082), Genebank AF180519 [GABA (A) receptors associated protein like 3], gene registration number ( Genebank) AB007870 (nucleoporin like 1). The biomarker of claim 1, wherein the expression of the following genes is reduced by exposure to toxaphene: Genebank XM_940101 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 11], Genebank XM_938617 {PREDICTED: Homo sapiens hypothetical protein LOC649542 (LOC649542), mRNA [XM_938617] }, Genebank XM_936688 {PREDICTED: Homo sapiens similar to Ceruloplasmin precursor (Ferroxidase) (LOC441368), mRNA [XM_926222]}, Genebank XM_935655 [Rap guanine nucleotide exchange factor (GEF) 5], Genebank XM_372002 [amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2 pseudogene], Genebank U68494 [Solute carrier family 30 (zinc transporter), member 1], Genebank (Genebank) NR_002932 (glutathione S-transferase M1 pseudogene), Genebank NR_002187 (hypothetical protein LOC286016), Genebank NM_203481 (hypothetical LOC403340), Genebank NM_201523 (kinesin ligh t chain 4), Genebank NM_199337 (similar to RIKEN cDNA 1810059G22), Genebank NM_199327 [sprouty homolog 1, antagonist of FGF signaling (Drosophila)], Genebank NM_198504 (progestin) and adipoQ receptor family member IX), Genebank NM_198252 [gelsolin (amyloidosis, Finnish type)], Genebank NM_183075 (cytochrome P450, family 2, subfamily U, polypeptide 1), gene registration number ( Genebank) NM_182908 [dehydrogenase / reductase (SDR family) member 2], Genebank NM_182760 (sulfatase modifying factor 1), Genebank NM_181738 (peroxiredoxin 2), Genebank NM_177550 [solute carrier family 13 (sodium-dependent citrate transporter), member 5], Genebank NM_176787 (phosphatidylinositol glycan anchor biosynthesis, class N), Genebank NM_175887 (proline rich 15), Gene accession number (Genebank) ) NM _173500 (tau tubulin kinase 2), gene registration number (Genebank) NM_173216 (ST6 beta-galactosamide alpha-2,6-sialyltranferase 1), gene registration number (Genebank) NM_172350 (CD46 molecule, complement regulatory protein), gene registration number ( Genebank) NM_172234 {Homo sapiens interleukin 17 receptor B (IL17RB), transcript variant 2, mRNA [NM_172234]}, Genebank NM_172164 [nuclear autoantigenic sperm protein (histone-binding)], Genebank number NM_153631 (homeobox A3), Genebank NM_153482 {Homo sapiens interleukin 17 receptor E (IL17RE), transcript variant 4, mRNA [NM_153482]}, Genebank NM_153344 {Homo sapiens chromosome 6 open reading frame 141 ( C6orf141), mRNA [NM_153344]}, Genebank NM_153186 (ankyrin repeat domain 15), Genebank NM_152764 (chromosome 16 open reading frame 73), Genebank NM_152722 (hepatocyte cell adhesion molecule), gene registration Genebank NM_152718 (von Willebrand factor C and EGF domains), Genebank NM_152379 (chromosome 1 open reading frame 131), Genebank NM_152308 (chromosome 16 open reading frame 75), Gene accession number (Genebank) NM_152299 (non-SMC condensin II complex, subunit H2), Gene Registration Number (Genebank) NM_148979 (cathepsin H), Gene Registration Number (Genebank) NM_145740 (glutathione S-transferase A1), Gene Registration Number (Genebank) NM_144966 (FRAS1 related extracellular matrix 1), Genebank NM_144595 (SLAIN motif family, member 1), Genebank NM_138730 (high mobility group nucleosomal binding domain 3), Genebank NM_138476 (magnesium -dependent phosphatase 1), Genebank NM_130806 (relaxin / insulin-like family peptide receptor 2), Genebank NM_058186 (family with sequence similarity 3, member B), Genebank NM_057091 (artemin), Genebank NM_054113 (calcium and integrin binding family member 3), Genebank NM_052968 (apolipoprotein AV), Genebank NM_033515 (Rho GTPase activating protein 18), Genebank (Genebank) NM_033502 (transcriptional regulating factor 1), Genebank NM_033380 [collagen, type IV, alpha 5 (Alport syndrome)], Genebank NM_033133 (2 ', 3'-cyclic nucleotide 3' phosphodiesterase), Genebank (Genebank) NM_031966 (cyclin B1), Genebank (Genebank) NM_031942 (cell division cycle associated 7), Genebank (Genebank) NM_031311 (carboxypeptidase, vitellogenic-like), Genebank NM_030919 ( family with sequence similarity 83, member D), Genebank NM_024743 (UDP glucuronosyltransferase 2 family, polypeptide A3), Genebank NM_024709 (chromosome 1 open reading frame 115), Genebank NM_02 4103 [solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 23], Genebank number NM_021871 (fibrinogen alpha chain), gene number (Genebank) NM_021139 (UDP glucuronosyltransferase 2 family, polypeptide B4), gene number (Genebank) NM_021069 (sorbin and SH3 domain containing 2), Genebank NM_020995 (haptoglobin-related protein), Genebank NM_020548 [diazepam binding inhibitor (GABA receptor modulator, acyl-Coenzyme A binding protein)], Genebank NM_020530 (oncostatin M), Genebank NM_020248 (catenin, beta interacting protein 1), Genebank NM_019101 (apolipoprotein M), Genebank NM_018663 (peroxisomal membrane protein 2, 22kDa), gene Genebank NM_018647 (tumor necrosis factor receptor superfamily, member 19), Genebank NM_018571 [amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2], gene registration number (Geneb) ank) NM_018410 (hypothetical protein DKFZp762E1312), Genebank NM_018136 [asp (abnormal spindle) homolog, microcephaly associated (Drosophila)], Genebank NM_017915 (chromosome 12 open reading frame 48), gene registration number (Genebank) NM_017899 (tescalcin), Genebank NM_017893 [sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4G], Genebank NM_017855 (odontogenic , ameloblast asssociated, Genebank NM_017779 (DEP domain containing 1), Genebank NM_017770 [elongation of very long chain fatty acids (FEN1 / Elo2, SUR4 / Elo3, yeast) -like 2], Genebank No. NM_017763 (ring finger protein 43), Genebank No. NM_017410 (homeobox C13), Genebank No. NM_016824 [adducin 3 (gamma)], Genebank No. NM_016619 (placenta) -specific 8), gene registration number ( Genebank) NM_016618 (lysine-rich coiled-coil 1), Genebank NM_016343 [centromere protein F, 350 / 400ka (mitosin)], Genebank NM_016297 (prenylcysteine oxidase 1), Gene Registration Number ( Genebank) NM_016256 (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase), Gene Registration Number (Genebank) NM_015974 (crystallin, lambda 1), Gene Registration Number (Genebank) NM_015917 (glutathione S-transferase kappa 1), Gene Registration Genebank NM_015471 [NSL1, MIND kinetochore complex component, homolog (S. cerevisiae)], Genebank NM_015385 (sorbin and SH3 domain containing 1), Genebank NM_015277 (neural precursor cell expressed, developmentally down-regulated 4-like), Genebank NM_015261 ( non-SMC condensin II complex, subunit D3), Genebank NM_015071 (Rho GTPase activating protein 26), Genebank NM_015008 (transmembrane and coiled-coil domain family 1), Genebank (Genebank) NM_014762 (24-dehydrocholesterol reductase), Genebank (Genebank) NM_014430 (cell death-inducing DFFA-like effector b), Gene Registration Number (Genebank) NM_014333 (cell adhesion molecule 1), Gene Registration Number (Genebank) NM_014298 {quinolinate phosphoribosyltransferase [nicotinate-nucleotide pyrophosphorylase (carboxylating)], Genebank NM_014176 [ubiquitin-conjugating enzyme E2T (putative)], Genebank NM_014109 (ATPase family, AAA domain containing 2) , Genebank NM_013282 (ubiquitin-like, containing PHD and RING finger domains, 1), Genebank NM_012484 [hyaluronan-mediated motility receptor (RHAMM)], Genebank NM_012288 (translocation associated membrane protein 2), Genebank NM_007256 (solute carrier organic anion transporter family, member 2B1), Genebank NM_007111 (transcription factor Dp-1), Genebank NM_006876 (UDP- GlcNAc: betaGal beta-1,3-N-acetylglucosaminyltransferase 1), Genebank NM_006863 [leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 1], Genebank NM_006821 (acyl CoA thioesterase 2), Genebank NM_006744 (retinol binding protein 4, plasma), Genebank NM_006579 [emopamil binding protein (sterol isomerase)], Genebank NM_006546 (insulin-like growth factor 2 mRNA bind ing protein 1), Genebank NM_006472 (thioredoxin interacting protein), Genebank NM_006461 (sperm associated antigen 5), Genebank NM_006403 (neural precursor cell expressed, developmentally down-regulated 9 ), Genebank NM_006079 (Cbp / p300-interacting transactivator, with Glu / Asp-rich carboxy-terminal domain, 2), Genebank NM_006055 [LanC lantibiotic synthetase component C-like 1 (bacterial) ], Genebank NM_005940 [matrix metallopeptidase 11 (stromelysin 3)], Genebank NM_005915 (minichromosome maintenance complex component 6), Genebank NM_005767 (purinergic receptor P2Y, G-protein coupled) , 5), Genebank NM_005733 (kinesin family member 20A), Genebank NM_005631 [smoothened homolog (Drosophila)], Genebank NM_005573 (lamin B1), Genebank (Genebank) ) NM_005567 (lectin, galactoside-binding, soluble, 3 binding protein), Genebank NM_005566 (lactate dehydrogenase A), Genebank NM_005502 [ATP-binding cassette, sub-family A (ABC1), member 1], Genebank NM_005432 (X-ray repair complementing defective repair in Chinese hamster cells 3), Genebank NM_005271 (glutamate dehydrogenase 1), Genebank NM_005165 (aldolase C, fructose) -bisphosphate), Gene Registration Number (Genebank) NM_005143 (haptoglobin), Gene Registration Number (Genebank) NM_005063 [stearoyl-CoA desaturase (delta-9-desaturase)], Gene Registration Number (Genebank) NM_005045 (reelin), Gene Registration Number (Genebank) NM_005030 [polo-like kinase 1 (Drosophila)], gene accession number (Genebank) NM_005021 (ectonucleotide pyrophosphatase / phosphodiesterase 3), gene accession number (Genebank) NM_004884 (putative neuronal cell adhesion molecule), gene registration number (Genebank) ) NM_004772 (chromosom e 5 open reading frame 13), Genebank NM_004701 (cyclin B2), Genebank NM_004683 [regucalcin (senescence marker protein-30)], Genebank NM_004640 (HLA-B associated transcript 1), Genebank NM_004591 [chemokine (CC motif) ligand 20], Genebank NM_004508 (isopentenyl-diphosphate delta isomerase 1), Genebank NM_004428 (ephrin-A1), Genebank NM_004252 [solute carrier family 9 (sodium / hydrogen exchanger), member 3 regulator 1], Genebank NM_004164 (retinol binding protein 2, cellular), Genebank NM_004107 (Fc fragment of IgG, receptor, transporter, alpha), Genebank NM_004086 [coagulation factor C homolog, cochlin (Limulus polyphemus)], Genebank NM_003713 (phosphatidic acid phosphatase type 2B), gene registration number ( Genebank) NM_003707 [RuvB-like 1 (E. coli)], Genebank NM_003667 (leucine-rich repeat-containing G protein-coupled receptor 5), Genebank NM_003634 [nipsnap homolog 1 (C. elegans)], Genebank (Genebank) NM_003559 (phosphatidylinositol-4-phosphate 5-kinase, type II, beta), Genebank NM_003488 [A kinase (PRKA) anchor protein 1], Genebank NM_003483 (high mobility group AT-hook 2 ), Genebank NM_003270 (tetraspanin 6), Genebank NM_003243 (transforming growth factor, beta receptor III), Genebank NM_003216 (thyrotrophic embryonic factor), Genebank (Genebank) NM_003118 [secreted protein, acidic, cysteine-rich (osteonectin)], gene registration number (Genebank) NM_003104 (sorbitol dehydrogenase), gene registration number (Genebank) NM_003022 (SH3 domain binding glutamic acid-rich protein like), gene registration number ( Genebank) NM_002998 (syndecan 2), Gene Registration Number (Ge nebank) NM_002959 (sortilin 1), Genebank NM_002860 (aldehyde dehydrogenase 18 family, member A1), Genebank NM_002758 (mitogen-activated protein kinase kinase 6), Genebank number NM_002729 (Genebank) hematopoietically expressed homeobox, Genebank NM_002630 [progastricsin (pepsinogen C)], Genebank NM_002611 (pyruvate dehydrogenase kinase, isozyme 2), Genebank NM_002592 (proliferating cell nuclear antigen), Genebank No. NM_002567 (phosphatidylethanolamine binding protein 1), Genebank No. NM_002508 (nidogen 1), Genebank No. NM_002413 (microsomal glutathione S-transferase 2), Genebank No. NM_002389 (CD46 molecule, complement regulatory protein), Genebank NM_002388 (minichromosome maintenance complex component 3), Genebank NM_002358 [MAD2 mitotic arrest deficient- like 1 (yeast)], Genebank NM_002340 [lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase)], Genebank NM_002334 (low density lipoprotein receptor-related protein 4), Gene accession number (Genebank) NM_002317 (lysyl oxidase), Genebank (Genebank) NM_002083 [glutathione peroxidase 2 (gastrointestinal)], Genebank (Genebank) NM_001948 (dUTP pyrophosphatase), Genebank (Menebank) NM_001914 [cytochrome b5 type A microsomal)], Genebank NM_001872 [carboxypeptidase B2 (plasma)], Genebank NM_001815 (carcinoembryonic antigen-related cell adhesion molecule 3), Genebank NM_001809 (centromere protein A), Genebank NM_001789 [cell division cycle 25 homolog A (S. pombe), Genebank NM_001786 (cell division cycle 2, G1 to S and G2 to M), Genebank NM_001756 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6], Genebank NM_001712 [carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)], Genebank NM_001461 (flavin containing monooxygenase 5), Genebank NM_001444 [fatty acid binding protein 5 (psoriasis-associated)], Genebank NM_001412 (eukaryotic translation initiation factor 1A, X-linked), Genebank NM_001360 (7-dehydrocholesterol reductase), Genebank NM_001359 ( 2,4-dienoyl CoA reductase 1, mitochondrial), Genebank NM_001311 [cysteine-rich protein 1 (intestinal)], Genebank NM_001237 (cyclin A2), Genebank NM_001182 (Genebank) aldehyde dehydrogenase 7 family, member A1), Genebank NM_001150 [alanyl (membrane) aminopeptidase N, aminopeptidase M, microsomal aminopeptidase, CD13, p150)], Genebank NM_001134 (alpha-fetoprotein), Genebank (Genebank) ) NM_001116 (adenylate cyclase 9), Genebank (Genebank) NM_001077 (UDP glucuronosyltransferase 2 family, polypeptide B17), Genebank (Genebank) NM_001075 (UDP glucuronosyltransferase 2 family, polypeptide B10), Gene registration number (Genebank) NM_001074 UDP glucuronosyltransferase 2 family, polypeptide B7), genebank NG_001073 (UDP glucuronosyltransferase 2 family, polypeptide B11), genebank NM_001072 (UDP glucuronosyltransferase 1 family, polypeptide A6), generegistration number (Genebank1) (thymidylate synthetase), Genebank NM_001067 (topoisomerase (DNA) II alpha 170kDa), Genebank NM_001040152 (paternally expressed 10), Genetic Genebank NM_001024074 (histamine N-methyltransferase), Genebank NM_001017395 (transmembrane and coiled-coil domain family 1), Genebank NM_001012271 [baculoviral IAP repeat-containing 5 (survivin)], Genebank NM_001010983 (glycosyltransferase 8 domain containing 1), Genebank NM_001005414 {Homo sapiens ZW10 interactor (ZWINT), transcript variant 4, mRNA [NM_001005414]}, Genebank NM_001005333 (melanoma antigen family D, 1), Genebank NM_001004320 (hypothetical protein LOC392636), Genebank NM_001003845 (Sp5 transcription factor), Genebank NM_001001290 (solute carrier family 2 (facilitated glucose transporter) , member 9], Genebank NM_000953 (prostaglandin D2 receptor (DP)), Genebank NM_000859 (3-hydroxy-3-methylglutaryl-Coenzyme A reductase), Gene Registration Number (Genebank) NM_000851 (glutathione S-transferase M5), Genebank NM_000847 (glutathione S-transferase A3), Gene Registration Number (Genebank) NM_000791 (dihydrofolate reductase), Gene Registration Number (Genebank) NM_000790 [dopa decarboxylase (dopa decarboxylase (Genebank) aromatic L-amino acid decarboxylase)], Genebank NM_000784 (cytochrome P450, family 27, subfamily A, polypeptide 1), Genebank NM_000716 (complement component 4 binding protein, beta), Gene accession number (Genebank) NM_000689 (aldehyde dehydrogenase 1 family, member A1), Genebank NM_000672 [alcohol dehydrogenase 6 (class V)], Genebank NM_000671 [alcohol dehydrogenase 5 (class III), chi polypeptide] , Genebank NM_000638 (vitronectin), Genebank NM_000624 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5], Genebank NM_000509 (fibrinogen gamma chain ), U Genebank NM_000495 [collagen, type IV, alpha 5 (Alport syndrome)], Genebank number (Genebank) NM_000483 (apolipoprotein C-II), Genebank number (Genebank) NM_000457 (hepatocyte nuclear factor 4, alpha) , Gene registration number (Genebank) NM_000384 [apolipoprotein B (including Ag (x) antigen)], gene registration number (Genebank) NM_000371 [transthyretin (prealbumin, amyloidosis type I)], gene registration number (Genebank) NM_000365 (triosephosphate isomerase 1 ), Genebank NM_000354 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 7], Genebank NM_000313 [protein S (alpha)], Genebank (Genebank) NM_000301 (plasminogen), Genebank (Genebank) NM_000277 (phenylalanine hydroxylase), Genebank (Genebank) NM_000253 (microsomal triglyceride transfer protein), Genebank (Genebank) NM_000211 [integrin, beta 2 (complement component 3 receptor 3 and 4 subunit)], heredity Genebank NM_000204 (complement factor I), Genebank NM_000185 [serpin peptidase inhibitor, clade D (heparin cofactor), member 1], Genebank NM_000166 (gap junction protein, beta 1, 32 kDa), Genebank NM_000142 [fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)], Genebank NM_000130 [coagulation factor V (proaccelerin, labile factor)], Genebank NM_000064 (complement component 3), gene registration number (Genebank) NM_000042 [apolipoprotein H (beta-2-glycoprotein I)], gene registration number (Genebank) NM_000040 (apolipoprotein C-III), gene registration number (Genebank) NM_000039 (apolipoprotein AI) ), Genebank NM_000029 [angiotensinogen (serpin peptidase inhibitor, clade A, member 8)], Genebank NM_000014 (alpha-2-macroglobulin), Genebank M10036 (triosephosphate isomerase 1 ), Gene Registration No. (Genebank) CR627122 [MRNA; cDNA DKFZp779M2422 (from clone DKFZp779M2422)], Genebank CR625412 [acidic (leucine-rich) nuclear phosphoprotein 32 family, member A], Genebank CR624291 (CDNA: FLJ22515 fis, clone HRC12122, highly similar to AF052101 Homo sapiens clone 23872 mRNA sequence), Genebank CR605719 [Full-length cDNA clone CS0DK002YG10 of HeLa cells Cot 25-normalized of Homo sapiens (human)], Genebank CR603982 [MRNA; cDNA DKFZp313B1017 (from clone DKFZp313B1017)], Genebank number BX405503 (Alpha-fetoprotein), Gene accession number (Genebank) BU783246 (in01c10.y1 Human insulinoma Homo sapiens cDNA clone IMAGE: 6123258 5 'similar to SWMANAD11766_ ALCOHOL DEHYDROGENASE CLASS III CHI CHAIN;, mRNA sequence.), Genebank BM928667 (Transcribed locus), Genebank BG591978 [Apolipoprotein H (beta-2-glycoprotein I)], Genebank (Genebank) ) BC067900 (hypothetical LOC149837), Genebank BC064969 (Acidic (leucine-rich) nuclear phosphoprotein 32 family, member A), Genebank BC050733 [ATP-binding cassette, sub-family C (CFTR / MRP), member 6], gene registration number (Genebank) BC050292 (MGC44478), gene registration number (Genebank) BC039065 [alcohol dehydrogenase 6 (class V)], gene registration number (Genebank) BC027988 (hypothetical protein LOC253842), gene registration Genebank BC006267 (asparaginase like 1) Genebank AK123483 (CDNA FLJ41489 fis, clone BRTHA2004582), Genebank AK095855 (CDNA clone IMAGE: 4513453), Genebank AF132203 (PRO1933), Genebank AF118092 ( predicted protein of HQ2061; Homo sapiens PRO2061 mRNA, complete cds.), Genebank AF007149 (hypothetical protein LOC257407). All of the nucleic acid sequences of any one or more genes selected from the biomarkers of claim 1; Or an oligonucleotide that is a fragment of the gene; Or a microarray chip for confirming exposure to toxaphene, in which its complementary strand molecules are integrated. The method of claim 4, wherein the oligonucleotide; Or a complementary strand molecule thereof, comprising 15 to 50 nucleic acids of the biomarker. The method of claim 5, wherein the oligonucleotide; Or a complementary strand thereof, wherein the microarray chip comprises 15 to 30 nucleic acids of the biomarker. RNA samples isolated from somatic cells of subjects (experimental group) and control subjects suspected of exposure to toxaphene. 1) labeling the experimental and control groups with different fluorescent materials while synthesizing with cDNA; 2) hybridizing cDNA labeled with different fluorescent materials of step 1) with the DNA microarray chip of claim 4; 3) analyzing the reacted DNA microarray chip of step 2); And 4) comparing the expression level of the gene on the DNA microarray chip with the control group in the analyzed data of step 3), the method of detecting the biomarker to confirm the exposure to toxaphene. 8. The method of claim 7, wherein said somatic cells are liver or cells derived from liver cancer cells and tissues. The method of claim 7, wherein the fluorescent material of step 2) is selected from the group consisting of Cy3, Cy5, poly L-lysine-fluorescein isothiocyanate (FITC), rhodamine-B-isothiocyanate (RITC), and rhodamine (rhodamine) Characterized in that the method. RNA samples isolated from somatic cells of subjects (experimental group) and control subjects suspected of exposure to toxaphene. 1) performing real-time reverse transcript polymerase chain reaction (RT-PCR) on the isolated RNA using a pair of primers complementary to the biomarker gene of claim 1 and capable of amplifying the biomarker gene ; And 2) detecting the biomarker to confirm exposure to toxaphene, comprising comparing the amount of gene product of step 1) with a control. The method of claim 10, wherein the somatic cells are liver or cells derived from liver cancer cells and tissues. 11. The method of claim 10, wherein the primer pair of step 1) is a 15-50mer long forward and reverse primer pair designed to have an amplification product of the biomarker gene of 100-300 bp. 13. The method of claim 12, wherein the primer pairs are forward and reverse primer pairs of 15 to 30mers in length. A diagnostic kit for exposure to toxaphene, comprising the microarray chip of claim 4. The kit of claim 14 further comprising human somatic cells. The kit of claim 15, wherein the somatic cells are cells derived from liver or liver cancer cells and tissues. The kit of claim 16, wherein the liver cancer cells are HepG2. Claim 1 complementary to the biomarker gene, comprising a primer pair capable of amplifying the biomarker gene, kit for diagnosing exposure to toxaphene. 19. The kit of claim 18, wherein the primer pairs are 15-50mer long forward and reverse primer pairs designed to have an amplification product of the biomarker gene of 100-300 bp. The method of claim 20, wherein the primer pairs are forward and reverse primer pairs of 15 to 30mers in length. 19. The kit of claim 18, wherein said primer pair is selected from the group consisting of the following primer pairs 1-11. Primer pair 1: forward primer set forth in SEQ ID NO: 1 and reverse primer set forth in SEQ ID NO: 2; Primer pair 2: forward primer set forth in SEQ ID NO: 3 and reverse primer set forth in SEQ ID NO: 4; Primer pair 3: forward primer set forth in SEQ ID NO: 5 and reverse primer set forth in SEQ ID NO: 6; Primer pair 4: forward primer set forth in SEQ ID NO: 7 and reverse primer set forth in SEQ ID NO: 8; Primer pair 5: forward primer set forth in SEQ ID NO: 9 and reverse primer set forth in SEQ ID NO: 10; Primer pair 6: forward primer set forth in SEQ ID NO: 11 and reverse primer set forth in SEQ ID NO: 12; Primer pair 7: forward primer set forth in SEQ ID NO: 13 and reverse primer set forth in SEQ ID NO: 14; Primer pair 8: forward primer set forth in SEQ ID NO: 15 and reverse primer set forth in SEQ ID NO: 16; Primer pair 9: forward primer set forth in SEQ ID NO: 17 and reverse primer set forth in SEQ ID NO: 18; Primer pair 10: forward primer set forth in SEQ ID NO: 19 and reverse primer set forth in SEQ ID NO: 20; And, Primer pair 11: Forward primer set forth in SEQ ID NO: 21 and reverse primer set forth in SEQ ID NO: 22. 19. The kit of claim 18, further comprising human somatic cells. 23. The kit of claim 22, wherein said somatic cells are cells derived from liver or liver cancer cells and tissues. The kit of claim 23, wherein the liver cancer cells are HepG2.

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