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  

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

作　　者：张爱华[1] 陈强[1] 李健[1] 潘雪莉[1] 赵转地[1] 黄晓欣[2] 岑笃才[2] 

机构地区：[1]贵阳医学院公共卫生学院,贵州贵阳550004 [2]解放军第44医院,贵州贵阳550009

出　　处：《环境与职业医学》2008年第5期425-428,共4页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学基金资助项目(编号：30460123，30760225);贵州省科研基金及省长基金(黔科合重大专项字[2006]6016)

摘　　要：[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MGMTmRNA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,MGMTmRNA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MGMTmRNA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。[ Objective ] To detect the Promoter hypermethylation of the DNA repair gone 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 hybridization was performed to detect the mRNA expression in skin of 61 victims of arsenism. [ Results ] ① The positive rate of MGMT methylation in case group was 40.4% vs. 2.91% in control group; The positive rate of the Promoter methylation of MGMT were gradually increased as the skin pathological changes grew worse. Among the group of lower-grade, medium and higher-grade group, the positive rate of methylation was 22.73%, 39.02% and 52.78% respectively, In non-carcinoma and carcinoma group, the positive rate was 27.78%and 65.00% respectively, they all were higher than the control group（ P 〈 0.05 or P 〈 0.01 ）. ②Along with the development of skin lesion in victims of arsenism, the expression rate of MGMT mRNA was decreased gradually. The expression rate in non-carcinoma group and carcinoma group was 71.05% and 30.43%, the difference between them was significantly （P 〈 0.01 ）. ③Relevance analysis showed that promoter hypermethylation rate of MGMT ascending was relate with decreasing of the mRNA expression （ r=0.456, P=0.01 ）. [ Conclusion ] The Promoter hypermethylation of the MGMT is a early incident in the development of the arsenism and also in the process of canceration; and the Promoter hypermethylation of the MGMT maybe an important cause in the decreasing of transcription, the latter may be an important factor in the decreasing of protein activity.

关 键 词：燃煤污染型砷中毒 MGMT基因 原位杂交 DNA甲基化 

分 类 号：R114[医药卫生—卫生毒理学]