氯乙烯致DNA损伤与DNA修复基因甲基化

DNA damage and methylation of DNA repair gene in vinyl chloride-exposed workers

目的探讨氯乙烯职业接触的早期效应DNA损伤与O6-甲基鸟嘌呤-DNA甲基转移酶基因MG-MT、错配修复基因hMLH1启动子甲基化的关系。方法氯乙烯接触工人按淋巴细胞双核微核数分为DNA损伤组(72例)和非损伤组(43例),采用甲基化特异的PCR法检测修复基因的甲基化。结果hMLH1基因在DNA损伤组和非损伤组均未检测到甲基化,MGMT基因在DNA非损伤组未检测到甲基化,在DNA损伤组MGMT发生甲基化频率为6.9%(5/72)。结论在氯乙烯致DNA损伤阶段,可检出MGMT基因甲基化异常。

Objective To explore the relationship between DNA damage induced by vinyl chloride monomer（VCM）exposure and the promoter methylation of O^6-methylguanine-DNA methyltransferase gene MGMT as well as mismatch repair gene hMLH1.Methods VCM exposed workers were divided into DNA damage group（72 individuals）and control group（43 individuals）according to the frequency of cytokinesis-block micronucleus.Methylation-specific PCR（MSP）was used to analyze the repair gene promoter methylation status of peripheral blood lymphocytes from VCM exposed workers.Results The MSP results revealed that there was no detectable promoter methylation of hMLH1 in both DNA damaged group and non-damaged group.The frequency of MGMT promoter methylation was 6.9%（5/72）in DNA damaged group and 0% in non-damaged group.Conclusions The results suggest that the aberrant methylation of MGMT gene may occur during DNA damage reflecting the early adverse effect induced by VCM exposure.