关键词: hMSH2, 基因甲基化, 硫化镍, 反式-二氢二醇环氧苯并茈

Abstract: BACKGROUND＆AIM：To study the aberrant methylation of the hMSH2 gene promoter and its mRNA expression in the nickel sulfide (NiS) and anti-7,8,-dihydrodiol-9,10-epoxide benzo[a] pyrene(anti-BPDE) transformed 16HBE cells and to explore the possible epigenetic mechanism for NiS and anti-BPDE carcinogenesis. MATERIAL AND METHODS： DNA methylation patterns in the hMSH2 gene promoter were determined by methylation-specific PCR(MSP) assay and mRNA expression was analysed by RT-PCR assay. The results were compared with the non-transformed 16HBE cells which and the aberrant methylation cells were treated with demethylating agent 5-Aza-2′-deoxycytidine. RESULTS： The hypermethylation in CpG island of the hMSH2 gene promoter was indentified in the NiS and anti-BPDE transformed 16HBE cells; comparing with non-transformed cells, hMSH2 gene mRNA expression levels of the NiS and anti-BPDE transformed 16HBE cells were reduced; treatment of the hMSH2 with 5-Azac decreased the methylation. CONCLUSION： Hypermethylation in CpG island of the hMSH2 gene promoter is known to result in mRNA expression reducing and gene silencing probably, it may represent a possible epigenetic mechanism for NiS and anti-BPDE induced cells transformation and carcinogenesis. Reversible methylation offered an important evidence for phenotype inversion and drug treatment.

Key words: hMSH2 gene, methylation, nickel sulfide, anti-7, 8, -dihydrodiol-9, 10-epoxide benzo[a] pyrene