氯乙烯是一种以肝脏为靶器官的遗传毒性致癌物，我国现行职业卫生标准尚难以保护氯乙烯作业工人的健康，其遗传物质损伤程度显著高于一般人群。近年来遗传损伤检测正在向能反映损伤更早期的分子调控水平转移。一些研究表明氯乙烯暴露导致DNA损伤修复相关基因的高甲基化和基因表达沉默，并与遗传物质的损伤相关联。在化学物诱导的表观遗传调控机制中, DNA甲基转移酶（DNMTs）是化学物作用的重要靶点，氯乙烯导致的DNA甲基化异常是否与DNMTs过表达有关，还未见报道。本项目拟对氯乙烯作业工人暴露水平、遗传损伤进行综合评价的基础上，应用芯片技术绘制外周血全基因组DNA异常甲基化谱，筛查差异甲基化基因位点并加以验证；利用RNA干扰技术进行体外试验研究DNMTs过表达的调控作用，探讨环境-异常甲基化-遗传损伤之间的相关性以及在此过程中DNMTs的调控作用，为阐明氯乙烯致遗传物质损伤的机制以及寻找早期标志物提供依据。

Vinyl chloride is a genetically toxic carcinogen with the target organ of the liver. Our occupational health standard is still difficult to protect the health of many workers exposed to vinyl chloride. The damage of genetic material is significantly higher than that of the general population. In recent years, genetic damage detection is being able to respond to the earlier stages of molecular regulation. Some studies have shown that the hypermethylation of DNA damage associated with repair genes and gene silence induced by vinyl chloride, which in turn leads to genetic damage. In the case of chemical-induced epigenetic regulatory mechanisms, DNA methyltransferase (DNMTs) is an important target. Whether or not DNA methylation abnormalities caused by vinyl chloride are related to overexpression of DNMTs has not been reported. Based on the comprehensive evaluation of exposure and genetic damage of the occupational exposure to vinyl chloride, we will uses the chip technology to map the abnormal methylation spectrum of peripheral blood genome DNA and screen the differential methylation gene locus and verify it. The RNAi will be used to investigate the effect of DNMTs overexpression in vitro. This project will explore the correlation between environmental-abnormal methylation-genetic damage and the regulation of DNMTs in this process, and to elucidate the epigenetic mechanism of DNA damage and look for earlier biomarker of vinyl chloride.