Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
권호 표지

Identification of Hepatotoxicity Related Genes Induced by Hexachlorobenzne (HCB) in Human Hepatocellular Carcinoma (HepG2) Cells

  • Kim, Youn-Jung (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology) ;
  • Choi, Han-Saem (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology) ;
  • Song, Mee (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology) ;
  • Song, Mi-Kyung (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology) ;
  • Ryu, Jae-Chun (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology)
  • Published : 2009.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Hexachlorobenzene (HCB) is a bioaccumulative, persistent, and toxic pollutant. HCB is one of the 12 priority of Persistent Organic Pollutants (POPs) intended for global action by the United Nations Environment Program (UNEP) Governing Council. POPs are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. Some of HCB is ubiquitous in air, water, soil, and biological matrices, as well as in major environmental compartments. HCB has effects on various organs such as thyroid, bone, skin, kidneys and blood cells and especially, revealed strong toxicity to liver. In this study, we identified genes related to hepatotoxiciy induced by HCB in human hepatocellular carcinoma (HepG2) cells using microarray and gene ontology (GO) analysis. Through microarray analysis, we identified 96 up- and 617 down-regulated genes changed by more than 1.5-fold by HCB. And after GO analysis, we determined several key pathways which known as related to hepatotoxicity such as metabolism of xenobiotics by cytochrome P450, complement and coagulation cascades, and tight junction. Thus, our present study suggests that genes expressed by HCB may provide a clue for hepatotoxic mechanism of HCB and gene expression profiling by toxicogenomic analysis also affords promising opportunities to reveal potential new mechanistic markers of toxicity.

Keywords

References

  1. Ritter, L., Solomon, K. R. & Forget, J. Persistent organic pollutants. United Nations Environment Programme. (2007)
  2. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Hexachlorobenzene (Update). Public Health Service, U.S. Department of Health and Human Services. Atlanta, GA (1996)
  3. Braune, B. M. & Norstrom, R. J. Dynamics of organochlorine compound in herring gulls. III: Tissue distribution and bioaccumulation in Lake Ontario gulls. Environ Toxicol Chem 8: 957-968 (1989) https://doi.org/10.1002/etc.5620081015
  4. Lie, E. et al. Dose high organochlorine (OC) exposure impair the resistance to infection in polar bears (Ursus maritimus)? Part 2: Possible effect of OCs on mitogenand antigen-induced lymphocyte proliferation. J Toxicol Environ Health A 68:457-484 (2005) https://doi.org/10.1080/15287390590903685
  5. Sormo, E. G. et al. Thyroid hormone status in gray seal (Halichoerus grypus) pups from the Baltic Sea and the Atlantic Ocean in relation to organochlorine pollutants. Environ Toxicol Chem 24:610-616 (2005) https://doi.org/10.1897/04-017R.1
  6. Ezendam, J., Vos, J. G. & Pieters, R. Research articles mechanisms of hexachlorobenzene-induced adverse immune effects in brown norway rats. J Immunotoxicol 1:167-175 (2005) https://doi.org/10.1080/15476910490907026
  7. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for HCB Atlanta, GA, USA: U. S Department of Health and Human Services, Public Health Service, ATSDR (1997)
  8. Smith, A. G. & Cabral, J. R. Liver-cell tumours in rats fed hexachlorobenzene. Cancer Lett 11:169-172 (1980) https://doi.org/10.1016/0304-3835(80)90108-1
  9. Cabral, J. R., Mollner, T., Raitano, F. & Shubik, P. Carcinogenesis of hexachlorobenzene in mice. Int J Cancer 23:47-51 (1979) https://doi.org/10.1002/ijc.2910230110
  10. Cabral, J. R. & Shubik, P. Carcinogenic activity of hexachlorobenzene in mice and hamsters. IARC Sci Publ 77:411-416 (1986)
  11. Smith, A. G. & De Matteis, R. Drugs and porphyria. Clin Haematol 9:399-425 (1980)
  12. Elder, G. H. Porphyria cutanea tarda. Semin Liver Dis 18:67-75 (1998) https://doi.org/10.1055/s-2007-1007142
  13. San Martin de Viale, L. C., Viale, A. A., Nacht, S. & Grinstein, M. Experimental porphyria induced in rats by hexachlorobenzene. A study of the porphyrin excreted by urine. Clin Chim Acta 28:13-23 (1970) https://doi.org/10.1016/0009-8981(70)90155-5
  14. Gorman, N. et al. Uroporphyria in mice: thresholds for hepatic CYP 1A2 and iron. Hepatology 35:912-921 (2002) https://doi.org/10.1053/jhep.2002.32487
  15. Gross, U., Hoffmann, G. F. & Doss, M. O. Erythropoietic and hepatic porphyrias. J Inherit Metab Dis 23: 641-661 (2000) https://doi.org/10.1023/A:1005645624262
  16. Thunell, S. (Far) Outside the box: genomic approach to acute porphyria. Physiol Res 55:S43-S66 (2006)
  17. Gardlo, K. et al. Cytochrome p450A1 polymorphisms in a Caucasian population with porphyria cutanea tarda. Exp Dermatol 12:843-848 (2003) https://doi.org/10.1111/j.0906-6705.2003.00095.x
  18. Ezendam, J. et al. Toxicogenomics of subchronic hexachlorobenzene exposure in Brown Norway rats. Environ Health Perspect 112:782-791 (2004)
  19. Goetz, A. K. et al. Gene expression profiling in the liver of CD-1 mice to characterize the hepatotoxicity of triazole fungicides. Toxicol Appl Pharmacol 215: 274-284 (2006) https://doi.org/10.1016/j.taap.2006.02.016
  20. Soultati, A. & Dourakis, S. P. Coagulation disorders in liver diseases. Haema 9:31-44 (2006)
  21. Garred, P. Mannose-binding lectin genetics: from A to Z. Biochem Soc Trans 36:1461-1466 (2007) https://doi.org/10.1042/BST0361461
  22. Takahashi, K. Lessons learned from murine models of mannose-binding lectin deficiency. Biochem Soc Trans 36:1487-1490 (2008) https://doi.org/10.1042/BST0361487
  23. Benedicto, I. Hepatitis C virus envelope components alter localization of hepatocyte tight junction-associated proteins and promote occludin retention in the endoplasmic reticulum. Hepatology 48:1044-1053 (2008) https://doi.org/10.1002/hep.22465
  24. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55-63 (1983) https://doi.org/10.1016/0022-1759(83)90303-4
  25. Park, H. W. et al. Gene expression patterns of environmental chemicals in human cell lines using HazChem human array. BioChip J 3:65-70 (2009)