中文摘要
本课题以我国饮水型砷中毒病区为背景，开展地方性砷中毒发病特点与砷代谢模式多样性关系的分子流行病学研究。结果表明：砷暴露人群的砷代谢模式呈多样性；随着砷累积暴露剂量增高,尿砷排泄增加,但甲基化能力降低,发病风险增大；高砷暴露儿童甲基化能力高于成人，可能是儿童砷中毒易感性低于成人的重要原因；性别及砷代谢酶相关基因GSTO1 ,2和cyt19多态性对人群尿砷排泄和甲基化能力无显著影响；同一砷暴露个体在不同时间点其代谢模式发生改变，提示外源性因素特别是饮食因素可能起重要作用；砷暴露人群氧化应激状态与砷甲基化能力有关，甲基化能力强者，抗氧化能力增强，DNA氧化损伤减轻；高砷暴露可使人体抗氧化能力下降，且随砷暴露时间的延长而加重；上述相关基因多态性对砷暴露人群的氧化应激状态无显著影响；尿8-OHdG随砷暴露浓度升高而增加且变化敏感，提示该指标可作为砷致DNA氧化损伤的早期标志；尿MMA%水平与机体抗氧化能力呈负相关，与氧化损伤正相关，提示尿MMA%的检测可作为砷毒性评价的重要指标。该研究阐明了砷在高暴露人群和中毒患者中的代谢规律及分子机制，为深入研究慢性砷中毒发病机制和开展有效防治奠定了基础。
英文摘要
In this topic, the molecular epidemiology research which is the relationship between clinical features of endemic arsenic poisoning and diversity of arsenic methylation pattern is carried out in drinking water of endemic arsenism areas. The results show: the arsenic methylation patterns of arsenic exposing population is variety; With increased of high arsenic cumulative exposure level, the arsenic in urinary excretion is increased, but methylation capacity is decreased, the risk of arsenism is increased; Children have higher arsenic methylation ability than adults when exposed to the high levels of arsenic in drinking water, this may be the important reason that children's susceptibility of arsenic poisoning is lower than adults';Urinary excretion and methylation capacity are not significantly affected by gender, polymorphism of arsenic metabolic enzyme-associated genes GSTO-1, 2, and Cyt19. Metabolic patterns are changed at different time points individually which suggests exogenous factors especially dietary factors may play an important role;The oxidative stress status of arsenic-exposed population is closely related to arsenic methylation capacity, it seems that the high arsenic methylation capacity is involved in the mitigation of oxidative DNA lesions and th increase of anti-oxidants capacity induced by ar
结题摘要
本课题以我国饮水型砷中毒病区为背景，开展地方性砷中毒发病特点与砷代谢模式多样性关系的分子流行病学研究。结果表明：砷暴露人群的砷代谢模式呈多样性；随着砷累积暴露剂量增高,尿砷排泄增加,但甲基化能力降低,发病风险增大；高砷暴露儿童甲基化能力高于成人，可能是儿童砷中毒易感性低于成人的重要原因；性别及砷代谢酶相关基因GSTO1 ,2和cyt19多态性对人群尿砷排泄和甲基化能力无显著影响；同一砷暴露个体在不同时间点其代谢模式发生改变，提示外源性因素特别是饮食因素可能起重要作用；砷暴露人群氧化应激状态与砷甲基化能力有关，甲基化能力强者，抗氧化能力增强，DNA氧化损伤减轻；高砷暴露可使人体抗氧化能力下降，且随砷暴露时间的延长而加重；上述相关基因多态性对砷暴露人群的氧化应激状态无显著影响；尿8-OHdG随砷暴露浓度升高而增加且变化敏感，提示该指标可作为砷致DNA氧化损伤的早期标志；尿MMA%水平与机体抗氧化能力呈负相关，与氧化损伤正相关，提示尿MMA%的检测可作为砷毒性评价的重要指标。该研究阐明了砷在高暴露人群和中毒患者中的代谢规律及分子机制，为深入研究慢性砷中毒发病机制和开展有效防治奠定了基础。