TCE作用下肝细胞中SET相关的表观遗传调控机制研究

三氯乙烯（TCE）是一种工业上应用广泛的有机溶剂，也是一种环境污染物，具有遗传毒性和致癌等作用，主要通过呼吸道吸入和皮肤吸收进入机体，产生职业性危害，肝脏是TCE在体内的重要代谢场所和主要受损器官之一，目前TCE对肝脏损害的分子机制尚不清楚。我们前期发现TCE可诱导肝细胞SET表达上调。本研究拟在前期研究基础上，以正常肝细胞和SET缺陷肝细胞为受试细胞，通过液相色谱、串联质谱鉴定和生物信息学技术，结合表观遗传学研究方法，筛选和鉴定TCE作用下肝细胞中与SET相关的特异组蛋白和DNA甲基化修饰，探讨TCE作用下组蛋白和DNA甲基化修饰与SET表达调控之间的因果关系，并进一步阐明TCE作用下SET表达上调的表观遗传调控机制。寻找TCE毒性相关的表观遗传生物标志，为其应用于TCE职业人群的研究提供理论依据，也为建立更加快速、灵敏、高效的职业毒物和环境污染物安全性评价方法提供新思路。

Trichloroethylene (TCE) is a common industrial solvent and environmental contaminant. TCE exposure is shown to cause genetic toxicity and carcinogenesis through the skin exposure as well as the respiratory tract. The liver is a major site of TCE metabolism and a target organ damaged by TCE exposure. The mechanisms underlying TCE hepatoxicity remain largely unclear. Based on the initial study demonstrating that TCE exposure up-regulates SET expression in liver cells, by exposing the normal liver cells and SET-deficient liver cells to TCE, we are aimed to screen and identify SET-related specific histone and DNA methylation modifications in liver cells under the treatment of TCE by using HPLC, MS/MS analysis, bioinformatics in combination with epigenetics analysis. This study will be expected to clarify the potential cause-effect relationships between histone and DNA methylation modifications and SET expression and the epigenetic regulation mechanisms leading to SET up-regulation in response to TCE exposure. Moreover, This study will help to seek the epigenetic biomarkers of TCE toxicity that can be applied into the study on TCE occupation exposure populations and also provide new insights into establishing fast, sensitive, high-efficiency safety assessment methodologies for occupational toxicants and environmental pollutants.