砷致氧化损伤与p53和p16基因启动子区甲基化的关联研究

Association between oxidative damage induced by arsenic and p53,p16 promoters methylation

目的探讨砷所致的氧化损伤与其所引起的基因启动子区高甲基化的关联。方法于2013年12月,在贵州省燃煤污染型地方性砷中毒病区招募74名常驻居民为研究对象,检测尿砷、发砷及尿中8-羟基脱氧鸟苷(8-OH-d G)的水平以及p53、p16启动子区CpG位点甲基化的情况。结果在控制年龄、性别、吸烟、饮酒后,尿砷与尿中8-OH-d G水平间呈正相关(P<0.05)。p16基因启动子区+248位和+317位CpG位点甲基化率与尿砷水平呈正相关(P<0.05),+248、+261、+314、+317、+320、+391位CpG位点甲基化率与尿中8-OH-d G水平呈正相关(P<0.05)。p53基因启动子区-9位、-127位CpG位点甲基化率与尿中8-羟基脱氧鸟苷水平呈正相关关系(P<0.05),+80位CpG位点甲基化率与尿砷水平呈正相关(P<0.05)。结论砷介导的氧化应激与砷所致基因异常甲基化间存在一定关联,其相关机制需进一步探索。

Objective To explore the correlation between arsenic exposure,DNA methylation of p53,p16 and 8-hydrox-2-deoxyguanosine（8-OH-d G） in arsenic exposure residents. Methods A total of 72 arsenic-exposed resident subjects were recruited during December 2013. The samples of blood,urine and hair were collected from all the subjects. The arsenic levels in urine and hair,8-OH-d G levels in urine and DNA methylations of p53,p16 promoters were determined. Results Increased urinary arsenic levels were associated with increased urinary 8-OH-d G levels（P〈0.05）;Methylation of ＋248,＋317CpG site of p16 was associated with increased urinary arsenic levels and 8-OH-d G（P〈0.05）. Additionally, the increased levels of urinary 8-OH-dG were significantly associated with increased methylation of-9,-127 CpG site of p53（P 〈0.05）. The increased urinary arsenic levels were significantly associated with increased methylation of ＋80 CpG site of p53（P 〈0.05）.Conclusion The results of the present study suggest that arsenic exposure may induce oxidative damage and thereby interfere with DNA methylation.