Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
권호 표지

Action-mechanisms of Genetic Polymorphism in the CYP2E1 on Susceptibility to Polycyclic Aromatic Hydrocarbons

다환성방향족탄화수소 노출에 대한 감수성에 미치는 CYP2E1의 작용

  • Kang Hyuck-Joon (Department of Microbiology, Hanyang University College of Medicine) ;
  • Park Chang- Hwan (Department of Microbiology, Hanyang University College of Medicine) ;
  • Kang Jin Sun (Department of Microbiology, Hanyang University College of Medicine) ;
  • Dong Mi- Sook (Graduate School of Biotechnology, Korea University) ;
  • Yang Mihi (Department of Toxicology, College of Pharmacy, Sookmyung Women's University)
  • Published : 2005.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

Environmental polycyclic aromatic hydrocarbones (PAHs), which are formed during incomplete combustion of fossil fuels, are widely distributed in our environment. Human exposure to PAHs may occur through smoking, polluted air, food consumption and occupational contact. Urinary naphthols, 1-and 2-naphthol, have been suggested as route -specific biomarkers for exposure to airborne PAHs. Cytochrome p450 2E1 (CYP2E1) is known to be a great importance for the metabolism of organic solvents, which is a precacinogens with small molecular weight. This study describes the metabolic differences between PstI and RsaI polymorphisms (c1 allele: PstI-. RsaI+ ; c2 allele: PstI+, RsaI-) of CYP2E1 5-flanking region by genetically modified HepG2 cells, which overexpress the polymorphic regions. The results of CAT assay and western blot in the c2 allele overexpressed cells have higher activities than the cl allele over-expressing cells. However, the metabolism of naphthalene to 2-naphthol has no difference due to the two genotypes. In this study, we established the CYP2E1 polymorphic allele transduced HepG2 cells to screen susceptibility -differences in PAH exposure. In conclusion, the CYP2E1 polymorphism may hardly induce susceptibility differences in PAH exposure monitoring with urinary naphthols.

Keywords

References

  1. Coles B, Yang M, Lang NP and Kadlubar FF. Expression of hGSTP1 alleles in human lung and catalytic activity of the native protein variants towards 1-chloro-2, 4-dinitro benzene, 4-vinylpyridine and (+)-anti benzoaJpyrene-7, 8-diol-9, 10-oxide, Cancer Lett 2000; 156(2): 167-175 https://doi.org/10.1016/S0304-3835(00)00458-4
  2. Hu Y, Oscarson M, Johansson I, Yue QY, Dahl ML, Tabone M, Arinco S, Albano E and Ingelman-Sundberg M. Genetic polymorphism of human CYP2E1: characterization of two variant alleles, Mol Pharmacol 1997; 51(3): 370-376
  3. Hu Y, Hakkola J, Oscarson M and Ingelman-Sundberg M. Structural and functional characterization of the 5'-flanking region of the rat and human cytochrome P450 2E1 genes: identification of a polymorphic repeat in the human gene, Biochem Biophys Res Commun 1999; 263: 286-293 https://doi.org/10.1006/bbrc.1999.1362
  4. Kawamoto T, Koga M, Murata K, Matsuda S and Kodama Y. Effects of ALDH2, CYP1A1, and CYP-2E1 genetic polymorphisms and smoking and drinking habits on toluene metabolism in humans, Toxicol Appl Pharmacol 1995, 133(2): 295-304 https://doi.org/10.1006/taap.1995.1154
  5. Kawamoto T and Yang M. Genetic polymorphisms in metabolic enzymes and metabolism of carcinogens. In Hanaoka, T. (ed.) Search for black boxes of environment-induced cancers: Challenge of molecular epidemiology in occupational medicine. Institute of Occupational Science Press, Human science-frontier series 2000 [III], Japan, 1999; 137-152
  6. Kim H, Kim YD, Lee H, Kawamoto T, Yang M and Katoh T. Assay of 2-naphthol in human urine by high-performance liquid chromatography, J Chromatogr B Biomed Sci Appl 1999; 734: 211-217 https://doi.org/10.1016/S0378-4347(99)00350-3
  7. Kim YD, Lee CH, Nan HM, Kang JW and Kim H. Effects of genetic polymorphisms in metabolic enzymes on the relationships between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary 1-hydroxypyrene and 2-naphthol concentration, J Occup Health 2003; 45: 160-167 https://doi.org/10.1539/joh.45.160
  8. Kim YD, Todoroki H, Oyama T, Isse T, Matsumoto A, Yamaguchi T, Kim H, Uchiyama I and Kawamoto T. Identification of cytochrome P450 isoforms involved in 1-hydroxylation of pyrene, Environ Res 2004; 94: 262-266 https://doi.org/10.1016/S0013-9351(03)00134-8
  9. Morimoto T and Sabatini DD: Subcellular fractionation of rough microsomes. In Spector DL, Goldman RD and Leinwand LA (eds.) Cells: a laboratory manual, pp 37.1-37.22, USA: CSHL Press, 1998
  10. Ory DS, Neugeboren BA and Mulligan RC. A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes, Proc Natl Acad Sci. USA 1996; 93: 11400-11406 https://doi.org/10.1073/pnas.93.21.11400
  11. Park CH, Oh HY, Heo OS, Sohn SJ, Han ES, Kim JW, Eom MO, Kim SH, Kim JS and Ha KW. Genetic Toxicity of Ochratoxin A in Chineses hamster lung and VERO cells, ddy mice, and Drosophila melanogaster, J Korean Soc Microbiol 1998; 33: 441-450
  12. Schulte P and Perera FP. Molecular Epidemiology principles and practices, Academic press, London, UK, 1993
  13. Uematsu F, Ikawa S, Kikuchi H, Sagami I, Kanamaru R, Abe T, Satoh K, Motomiya M and Watanabe M. Restriction fragment length polymorphism of the human CYP2E1 (cytochrome P450IIE1) gene and susceptibility to lung cancer: possible relevance to low smoking exposure, Pharmacogenetics 1994; 4: 58-63 https://doi.org/10.1097/00008571-199404000-00002
  14. Watanabe J, Hayashi Sand Kawajiri K. Different regulation and expression of the human CYP2E1 gene due to the RsaI polymorphism in the 5'-flanking region, J Biochem (Tokyo) 1994; 116(2): 321-326
  15. Yang M, Koga M, Katoh T and Kawamoto T. A study for the proper application of urinary naphthols, new biomarkers for airborne polycyclic aromatic hydrocarbons, Arch Environ Contam Toxicol 1999; 36(1): 99-108 https://doi.org/10.1007/s002449900447
  16. Yang M, Kunugita N, Kitagawa K, Kang SH, Coles B, Kadlubar FF, Katoh T, Matsuno K and Kawamoto T. Individual differences in urinary cotinine levels in Japanese smokers: relation to genetic polymorphism of drug-metabolizing enzymes, Cancer Epidemiol Biomarkers Prev 2001; 10(6): 589-93
  17. Yang M, Coles BF, Delongchamp R, Lang NP and Kadlubar FF. Effects of the ADH3, CYP2E1, and GSTP1 genetic polymorphisms on their expressions in Caucasian lung tissue, Lung Cancer 2002; 38: 315-321 https://doi.org/10.1016/S0169-5002(02)00150-2