Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Gene Expression Profiles Related with TCDD-Induced Hepatotoxicity

  • Ryu, Yeon-Mi (Department of Biochemistry & Molecular biology, Korea University Medical School) ;
  • Kim, Ki-Nam (Department of Biochemistry & Molecular biology, Korea University Medical School) ;
  • Kim, Yu-Ri (Department of Biochemistry & Molecular biology, Korea University Medical School) ;
  • Sohn, Sung-Hwa (Department of Biochemistry & Molecular biology, Korea University Medical School) ;
  • Seo, Sang-Hui (Department of Biochemistry & Molecular biology, Korea University Medical School) ;
  • Lee, Seung-Ho (Department of Biochemistry & Molecular biology, Korea University Medical School) ;
  • Kim, Hye-Won (Department of Biochemistry & Molecular biology, Korea University Medical School) ;
  • Won, Nam-Hee (Department of Pathology, Korea University Medical School) ;
  • Kim, Meyoung-Kon (Department of Biochemistry & Molecular biology, Korea University Medical School)
  • Published : 2005.09.30
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Abstract

Toxicological studies have an object of detecting adverse effects of a chemical on an organism based on observed toxicity marker (i.e., serum biochemical markers and chemical-specific gene expression) or phenotypic outcome. To date, most toxicogenomic studies concentrated on hepatic toxicity. cDNA microarray analysis enable discrimination of the responses in animals exposed to different classes of hepatotoxicants. In an effort to further characterize the mechanisms of 2, 3, 7, 8,-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin)-mediated toxicity, comprehensive temporal-responsive microarray analyses were performed on hepatic tissue from Sprague-Dawley rats treated with TCDD. Hepatic gene expression profiles were monitored using custom DNA chip containing 490 cDNA clones related with toxicology. Gene expression analysis identified 26 features which exhibited a significant change. In this study, we observed that the genes related with oxidative stress in rats exposed to Dioxin, such as CYPIIA3 and glutathione S-transferase, were up-regulated at 24hr after exposure. In this study, we carried out to discover novel evidence for previously unknown gene expression patterns related to mechanism of hepatic toxicity in rats exposed to dioxin, and to elucidate the effects of dioxin on the gene expression after exposure to dioxin.

Keywords

References

  1. Minami, K. et al. Relationship between hepatic gene expression profiles and hepatotoxicity in five typical hepatotoxicant-administered rats. Toxicol. Sci. 87(1), 296-305 (2005) https://doi.org/10.1093/toxsci/kfi235
  2. Heijne, W.H. et al. Profiles of metabolites and gene expression in rats with chemically induced hepatic necrosis. Toxicol. Pathol. 33(4), 425-33 (2005) https://doi.org/10.1080/01926230590958146
  3. Bulera, S.J. et al. RNA expression in the early characterization of hepatotoxicants in Wistar rats by high-density DNA microarrays. Hepatology 33(5), 1239-1258 (2001) https://doi.org/10.1053/jhep.2001.23560
  4. Burczynski, M.E. et al. Toxicogenomics-based discrimination of toxic mechanism in HepG2 human hepatoma cells. Toxicol. Sci. 58(2), 399-415 (2000) https://doi.org/10.1093/toxsci/58.2.399
  5. Waring, J.F. et al. Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles. Toxicol. Appl. Pharmacol. 175(1), 28-42 (2001) https://doi.org/10.1006/taap.2001.9243
  6. Mandal, P.K. Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology. J. Comp. Physiol. 175, 221-230 (2005) https://doi.org/10.1007/s00360-005-0483-3
  7. Fisher, M.T., Nagarkatti, M. & Nagarkatti, P.S. Combined screening of thymocytes using apoptosisspecific cDNA array and promoter analysis yields novel gene targets mediating TCDD-induced toxicity. Toxicol. Sci. 78, 116-24 (2004) https://doi.org/10.1093/toxsci/kfh058
  8. Watanabe, H. et al. Comparative uterine gene expression analysis after dioxin and estradiol administration. J. Mol. Endocrinol. 33(3), 763-71 (2004) https://doi.org/10.1677/jme.1.01529
  9. Boverhof, D.R. et al. Temporal and dose-dependent hepatic gene expression patterns in mice provide new insights into TCDD-Mediated hepatotoxicity. Toxicol. Sci. 85, 1048-1063 (2005) https://doi.org/10.1093/toxsci/kfi162
  10. Couture, L.A., Abbott, B.D. & Birnbaum, L.S. A critical review of the developmental toxicity and teratogenicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin: recent advances toward understanding the mechanism. Teratology 42, 619-627 (1990) https://doi.org/10.1002/tera.1420420606
  11. Korkalainen, M., Tuomisto, J. & Pohjanvirta, R. Primary structure and inducibility by 2, 3, 7, 8-tetraclrodibenzo- p-dioxin (TCDD) of aryl hydrocarbon receptor repressor in a TCDD-sensitive and a TCDDresistant rat strain. Biochem. Biophys. Res. Commun. 315, 123-131 (2004) https://doi.org/10.1016/j.bbrc.2004.01.028
  12. Boverhof, D.R. et al. Temporal and dose-dependent hepatic gene expression patterns in mice provide new insights into TCDD-Mediated hepatotoxicity. Toxicol. Sci. 85, 1048-1063 (2005) https://doi.org/10.1093/toxsci/kfi162
  13. Davis, B.J., McCurdy, E.A., Miller, B.D., Lucier, G.W. & Tritscher, A.M. Ovarian tumors in rats induced by chronic 2, 3, 7, 8-tetrachlorodibenzo-pdioxin treatment. Cancer Res. 60, 5414-5419 (2000)
  14. Fletcher, N. et al. 2, 3, 7, 8-Tetrachlorodibenzo-pdioxin (TCDD) alters the mRNA expression of critical genes associated with cholesterol metabolism, bile acid biosynthesis, and bile transport in rat liver: A microarray study. Toxicol Appl. Pharmacol. 22, 207(1):1-24 (2005) https://doi.org/10.1016/0041-008X(72)90219-0
  15. Vawter, M.P. et al. Application of cDNA microarrays to examine gene expression differences in schizophrenia. Brain. Res. Bull. 55, 641-650 (2001) https://doi.org/10.1016/S0361-9230(01)00522-6
  16. Tanaka, T.S. et al. Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. Proc. Natl. Acad. Sci. 97, 9127-9132 (2000) https://doi.org/10.1073/pnas.97.16.9127
  17. Eisen, M.B., Spellman, P.T., Brown, P.O. & Botstein, D. Cluster analysis and display of genome-wide expression patterns. Proc. Natl. Acad. Sci. 95, 14863- 14868 (1998) https://doi.org/10.1073/pnas.95.25.14863
  18. Ishizuka, M., Yonemoto, J., Zaha, H., Tohyama, C. & Sone, H. Perinatal exposure to low doses of 2, 3, 7, 8- tetrachlorodibenzo-p-dioxin alters sex-dependent expression of hepatic CYP2C11. J. Biochem. Mol. Toxicol. 17, 278-85 (2003) https://doi.org/10.1002/jbt.10090
  19. Volz, D.C., Bencic, D.C., Hinton, D.E., Law, J.M. & Kullman, S.W. 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) induces organ- specific differential gene expression in male Japanese medaka (Oryzias latipes). Toxicol. Sci. 85, 572-584 (2005) https://doi.org/10.1093/toxsci/kfi109
  20. Adachi, J., Mori, Y., Matsui, S. & Matsuda, T. Comparison of gene expression patterns between 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin and a natural arylhydrocarbon receptor ligand, indirubin. Toxicol. Sci. 80, 161-169 (2004) https://doi.org/10.1093/toxsci/kfh129
  21. Puga, A., Maier, A. & Medvedovic, M. The transcriptional signature of dioxin in human hepatoma HepG2 cells. Biochem. Pharmacol. 60, 1129-1142 (2000) https://doi.org/10.1016/S0006-2952(00)00403-2
  22. Tan Z., Huang M., Puga A. & Xia Y. A critical role for MAP kinases in the control of Ah receptor complex activity. Toxicol. Sci. 82, 80-7 (2004) https://doi.org/10.1093/toxsci/kfh228
  23. Vezina C.M., Walker N.J. & Olson J.R. Subchronic exposure to TCDD, PeCDF, PCB126, and PCB153: effect on hepatic gene expression. Environ. Health Perspect. 112, 1636-1644 (2004) https://doi.org/10.1289/ehp.7253
  24. Schmidt, C.K. et al. 2, 3, 7, 8-tetrachlorodibenzo-pdioxin (TCDD) alters the endogenous metabolism of all-trans-retinoic acid in the rat. Arch. Toxicol. 77(7), 371-383 (2003) https://doi.org/10.1007/s00204-003-0457-8
  25. Mimura, J. & Fujii-Kuriyama, Y. Functional role of AhR in the expression of toxic effects by TCDD. Biochim. Biophys. Acta. 1619, 263-268 (2003) https://doi.org/10.1016/S0304-4165(02)00485-3
  26. Bagchi, D. et al. Comparative effects of TCDD, endrin, naphthalene and chromium (VI) on oxidative stress and tissue damage in the liver and brain tissues of mice. Toxicology 14, 73-82 (2002)
  27. Slezak, B.P., Diliberto, J.J. & Birnbaum, L.S. 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin-mediated oxidative stress in CYP1A2 knockout (CYP1A2-/-) mice. Biochem. Biophys. Res. Commun. 264(2), 376-379 (1999) https://doi.org/10.1006/bbrc.1999.1518
  28. Arpiainen, S., Raffalli-Mathieu, F., Lang, M.A., Pelkonen, O. & Hakkola, J. Regulation of the Cyp2a5 gene involves an aryl hydrocarbon receptor-dependent pathway. Mol. Pharmacol. 67(4), 1325-1333 (2005) https://doi.org/10.1124/mol.104.008078
  29. Rivera, S.P., Saarikoski, S.T. & Hankinson, O. Identification of a novel dioxin-inducible cytochrome P450. Mol. Pharmacol. 61(2), 255-259 (2002) https://doi.org/10.1124/mol.61.2.255
  30. Barouki, R. & Morel, Y. Repression of cytochrome P450 1A1 gene expression by oxidative stress: mechanisms and biological implications. Biochem. Pharmacol. 61(5), 511-516 (2001) https://doi.org/10.1016/S0006-2952(00)00543-8
  31. McMillian, M. et al. A gene expression signature for oxidant stress/reactive metabolites in rat liver. Biochem. Pharmacol. 68(11), 2249-2261 (2004) https://doi.org/10.1016/j.bcp.2004.08.003
  32. Pons, N., Pipino, S. & De Matteis F. Interaction of polyhalogenated compounds of appropriate configuration with mammalian or bacterial CYP enzymes. Increased bilirubin and uroporphyrinogen oxidation in vitro. Biochem. Pharmacol. 66(3), 405-414 (2003) https://doi.org/10.1016/S0006-2952(03)00284-3
  33. Nishimura, N. et al. Induction of metallothionein in the livers of female Sprague-Dawley rats treated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. Life Sci. 69(11), 1291-1303 (2001) https://doi.org/10.1016/S0024-3205(01)01212-7
  34. Bauman, J.W., Liu, J., Liu, Y.P. & Klaasse, C.D. Increase in metallothionein produced by chemicals that induce oxidative stress. Toxicol. Appl. Pharmacol. 110(2), 347-354 (1991) https://doi.org/10.1016/S0041-008X(05)80017-1
  35. Matsumura, F. On the significance of the role of cellular stress response reactions in the toxic actions of dioxin. Biochem. Pharmacol. 66(4), 527-540 (2003) https://doi.org/10.1016/S0006-2952(03)00157-6
  36. Kletzien, R.F., Harris, P.K. & Foellmi, L.A. Glucose- 6-phosphate dehydrogenase: a “housekeeping” enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress. FASEB J. 8(2), 174-181 (1994) https://doi.org/10.1096/fasebj.8.2.8119488
  37. Diez-Fernandez, C., Sanz, N. & Cascales, M. Changes in glucose-6-phosphate dehydrogenase and malic enzyme gene expression in acute hepatic injury induced by thioacetamide. Biochem. Pharmacol. 51(9), 1159-1163 (1996) https://doi.org/10.1016/0006-2952(96)00030-5
  38. Hori, M., Kondo, H., Ariyoshi, N., Yamada, H. & Oguri K. Species-specific alteration of hepatic glucose 6-phosphate dehydrogenase activity with coplanar polychlorinated biphenyl: evidence for an Ah-receptorlinked mechanism. Chemosphere. 35(5), 951-958 (1996) https://doi.org/10.1016/S0045-6535(97)00181-1
  39. Bartosiewicz, M., Penn, S. & Buckpitt, A. Applications of gene arrays in environmental toxicology: fingerprints of gene regulation associated with cadmium chloride, benzo(a)pyrene, and trichloroethylene. Environ. Health Perspect. 109(1), 71-74 (2001) https://doi.org/10.2307/3434924
  40. Vrana, K.E., Freeman, W.M. & Aschner, M. Use of Microarray Technologies in Toxicology Research. Neurotoxicology 24(3), 321-332 (2003) https://doi.org/10.1016/S0161-813X(02)00193-6