Environmental Mutagens and Carcinogens (한국환경성돌연변이발암원학회지)

Korean Environmental Mutagen Society (한국환경성돌연변이발암원학회)
권호 표지

Promoter Methylation and Expression of CYP1A2 in Dielhylnitrosamine-induced Mice liver Tumors

Diethylnitrosamine에 의하여 유발된 마우스 간 종양의 CYP1A2 메틸화와 발현

  • Jin, Bo-Hwan (College of Veterinary Medicine, Seoul National University) ;
  • Oh, Sae-Jin (College of Veterinary Medicine, Seoul National University) ;
  • Ryu, Doug-Young (College of Veterinary Medicine, Seoul National University)
  • Published : 2006.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Cytochrome P450 1A2 (CYP1A2) is a xenobiotic metabolizing enzyme that is tissue-specifically expressed in the mammalian liver. In this study, the extent of CYP1A2 promoter methylation was analyzed to determine its potential role in the regulation of CYP1A2 in diethylnitrosamine (DEN)-induced mouse liver tumors. CYP1A2 mRNA was under-expressed about three fold in DEN-induced liver tumors compared to age-matched control livers. The CYP1A2 promoter was hypermethylated in DEN-induced liver tumors compared to controls, especially in a promoter domain close to the coding region. These results suggest that promoter methylation is involved in the regulation of CYP1A2 in mouse liver tumors.

Keywords

References

  1. Botto, F., Seree, E., el Khyari, S., de Sousa, G., Massacrier, A., Placidi, M., Cau, P., Pellet, W., Rahmani, R. and Barra, Y. (1994). Tissue-specific expression and methylation of the human CYP2E1 gene. Biochem Pharmacol 48, 1095-103 https://doi.org/10.1016/0006-2952(94)90145-7
  2. Carrier, F., Chang, C.Y., Duh, J.L., Nebert, D.W. and Puga, A. (1994). Interaction of the regulatory domains of the murine Cyp1a1 gene with two DNA-binding proteins in addition to the Ah receptor and the Ah receptor nuclear translocator (ARNT). Biochem Pharmacol 48, 1767-78 https://doi.org/10.1016/0006-2952(94)90463-4
  3. Guengerich, F.P. and Shimada, T. (1991). Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem Res Toxicol 4, 391-407 https://doi.org/10.1021/tx00022a001
  4. Hammons, G.J., Yan-Sanders, Y., Jin, B., Blann, E., Kadlubar, F. F. and Lyn-Cook, B.D. (2001). Specific site methylation in the 5'-flanking region of CYP1A2 interindividual differences in human livers. Life Sci 69, 839-45 https://doi.org/10.1016/S0024-3205(01)01175-4
  5. Jaenisch, R. and Bird, A. (2003). Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33 Suppl, 245-54 https://doi.org/10.1038/ng1089
  6. Jin, B., Park, D.W., Nam, K.W., Oh, G.T., Lee, Y.S. and Ryu, D.Y. (2004). CpG methylation of the mouse CYP1A2 promoter. Toxicol Lett 152, 11-8 https://doi.org/10.1016/j.toxlet.2004.03.016
  7. Jin, B. and Ryu, D.Y. (2004). Regulation of CYP1A2 by histone deacetylase inhibitors in mouse hepatocytes. J Biochem Mol Toxicol 18, 131-2 https://doi.org/10.1002/jbt.20017
  8. Nakajima, M., Iwanari, M. and Yokoi, T. (2003). Effects of histone deacetylation and DNA methylation on the constitutive and TCDD-inducible expressions of the human CYP1 family in MCF-7 and HeLa cells. Toxicol Lett 144, 247-56 https://doi.org/10.1016/S0378-4274(03)00216-9
  9. Peterson, T.C., Gonzalez, F.J. and Nebert, D.W. (1986). Methylation differences in the murine P1450 and P3450 genes in wildtype and mutant hepatoma cell culture. Biochem Pharmacol 35, 2107-14 https://doi.org/10.1016/0006-2952(86)90577-0
  10. Robertson, K.D. (2002). DNA methylation and chromatin-unraveling the tangled web. Oncogene 21, 5361-79 https://doi.org/10.1038/sj.onc.1205609