慢性砷暴露致人体生物样品p53、p16启动子区甲基化的改变

发布时间：2018-01-22 08:34

本文关键词： 砷 DNA甲基化 p基因 p基因　出处：《环境与职业医学》2017年02期 　论文类型：期刊论文

【摘要】：[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P0.05);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P0.05)。[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。
[Abstract]:[Objective] to investigate the effect of arsenic exposure on methylation of p53 p16 promoter in human biological samples, and to explore the role of methylation of p53 p16 promoter DNA in arsenic pathogenicity. [Methods] 42 resident residents were selected as exposure group in the endemic arsenism area of coal-burning pollution in Guizhou Province, in addition, non-arsenic exposure villages about 12 km away from the endemic area were selected. 40 residents were selected as control group. Urine, blood and hair samples were collected under the principle of informed consent. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect arsenic in urine and hair, and p53 was detected by sulfite modified sequencing method (BSPs). Methylation of CP G site in p16 promoter region. [Results the average methylation rate of urinary arsenic and hair arsenic were 40.59 卤27.12 渭 g / g and 0.32 卤0.36 渭 g / g / g respectively in the exposed group. The average methylation rate of p53 was 8.32 卤1.51%. The methylation rates of CP G loci at positions 71, 42 and 109 in exposed group were 11.44 卤3.64 and 2.58 卤1.29% and 4.98 卤1.33%, respectively. All of them were higher than the control group (P 0.05). There was no significant difference in the average methylation rate of p16 and the methylation rate of each CP G site between the exposed group and the control group (all P 0.05). [Conclusion the methylation of CP G site in the promoter of p53 gene is related to arsenic exposure, and the DNA methylation induced by arsenic exposure may have site specificity.
【作者单位】：贵州医科大学环境污染与疾病监控教育部重点实验室;贵州医科大学公共卫生学院卫生毒理学教研室;中国人民解放军第44医院;
【基金】：国家自然科学基金(编号:81430077,81302394)
【分类号】：R114
【正文快照】： 砷是确认的人类致癌物,但其致病机制迄今未明[1]。现有研究提示,砷所致的表观遗传学改变,可能在其致病致癌中发挥重要作用[2-4]。DNA甲基化通过调节基因转录、印记等,在细胞分化、环境适应和疾病发生发展中扮演重要角色,是当前表观遗传学研究的热点领域之一[5-6]。研究证实砷

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