燃煤污染型砷中毒患者MGMT基因启动区甲基化及MGMT mRNA的表达

[目的]了解燃煤污染型砷中毒患者血中O^6-甲基鸟嘌呤-DNA甲基转移酶基因（MGMT基因）启动区甲基化及患者皮肤组织中MGMT mRNA转录表达的情况，探讨两者间关系及其在砷中毒发生发展乃至癌变中的作用。[方法]采用甲基化特异性PCR法（MSP）检测99例砷中毒患者和103例正常对照MGMT基因启动区甲基化情况；同时采用原位杂交技术检测其中61例砷中毒患者皮肤组织中MGMT mRNA的表达情况。[结果]①砷中毒组MGMT基因启动区甲基化阳性率为40．4％，对照组为2．91％；随病情加重砷中毒患者甲基化阳性率逐渐升高，轻、中、重度砷中毒组甲基化阳性率分别为22．73％、39．02％和52．78％，非癌变组与癌变组甲基化阳性率分别为27．78％和65．00％，均显著高于对照组（P〈0．05或P〈0．01）。②随着砷中毒患者皮肤病变的加重，MGMT mRNA阳性表达率逐渐降低，其表达率在非癌变组与癌变组分别为71．05％和30．43％，两组间差异有统计学意义（P〈0．01）。③MGMT基因启动区甲基化阳性率升高与该基因mRNA表达降低有关联（r=0．456，P=0．01）。[结论]MGMT基因启动区高甲基化是砷中毒发生发展乃至癌变发生的早期事件；MGMT基因启动区高甲基化可导致MGMT mRNA转录水平下降并可能是进一步导致蛋白活性降低的重要原因之一。

Study on the Promoter Hypermethylation of the DNA Repair Gene O~6-methylguanine-DNA Methyltransferase and mRNA Expression in Victims of Endemic Arsenism Caused by Coal-burning

[Objective]To detect the Promoter hypermethylation of the DNA repair gene O~6-methylguanine-DNA methyltransferase in blood and mRNA expression in skin of victims of endemic arsenism caused by coal-burning.To probe the relationship between them and the effect in the development of the arsenism and also in the process of canceration.[Methods] Methylation-specific PCR was performed to detect the Promoter hypermethylation of MGMT in peripheral blood of 99 victims of arsenism and 103 normal controls.And in situ ...