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[目的]了解砷暴露对人体生物样品中p53、p16启动子区甲基化的影响,探讨p53、p16启动子区DNA甲基化改变及在砷致病中的作用。[方法]于贵州省燃煤污染型地方性砷中毒病区,选择42名常驻居民为暴露组,另于距病区约12 km的非砷暴露村,选择40例居民作为对照组。在知情同意的原则下,采集受试对象尿液、血液和发样,使用电感耦合等离子体质谱(ICP-MS)法检测受试对象尿砷和发砷,采用亚硫酸盐修饰后测序法(BSP)法检测p53、p16启动子区Cp G位点甲基化情况。[结果]暴露组尿砷为(40.59±27.12)μg/g、发砷为(0.32±0.36)μg/g,p53平均甲基化率为(8.32±1.51)%,暴露组-71、+42、+109位Cp G位点甲基化率分别为(11.44±3.64)%,(2.58±1.29)%和(4.98±1.33)%,均高于对照组(均P<0.05);暴露组和对照组p16平均甲基化率和各Cp G位点甲基化率差异均无统计学意义(均P>0.05)。[结论]p53基因启动子区Cp G位点的甲基化与砷暴露有关,砷暴露所致的DNA甲基化可能存在位点的特异性。
[Objective] To understand the effect of arsenic exposure on the methylation of p53 and p16 promoter regions in human biological samples and to explore the changes of DNA methylation in p53 and p16 promoter regions and their roles in arsenism pathogenesis. [Method] In the endemic arsenism poisoning area of coal-burning pollution in Guizhou Province, 42 resident residents were selected as the exposure group, and the other 40 residents were selected as the control group in the non-arsenic exposed village about 12 km away from the ward. Under the principle of informed consent, urine, blood and hair samples of the subjects were collected, urine arsenic and arsenic were determined by inductively coupled plasma mass spectrometry (ICP-MS) and sulfite modified sequencing BSP) assay was used to detect the CpG site methylation in p53 and p16 promoter regions. [Results] The urinary arsenic in the exposed group was (40.59 ± 27.12) μg / g, the hair arsenic was (0.32 ± 0.36) μg / g, the average methylation rate of p53 was (8.32 ± 1.51)%, (P <0.05). The methylation rates of + CpG at + 109 were (11.44 ± 3.64)%, (2.58 ± 1.29)% and (4.98 ± 1.33)%, respectively The average methylation rate of p16 in control group and the methylation rate of each CpG site showed no significant difference (all P> 0.05). [Conclusion] Methylation of CpG site in p53 gene promoter is related to arsenic exposure. There may be site-specific DNA methylation induced by arsenic exposure.