ABSTRACT

Trichloroacetic acid (TCA) is a common non-volatile by-product of chlorination disinfection for drinking water. It is necessary to know the epigenetic toxicity and mechanisms for establishing safe exposure limit for environmental TCA exposure. This study explored the histone modification variations of TCA-treated human hepatocytes L-02 at different time and concentrations. TCA (0.1 mM, 0.3 mM and 0.9 mM) had an inhibitory effect on the growth of L-02 cells, with no significant changes in morphology. Treated with TCA for 24 h and 48 h, L-02 cells showed decreased mRNA and protein level of histone deacetylases (HDACs), but increased after 72 h. The downregulation of HDACs in early stage of TCA exposure might be one of the important reasons for the increase of H3K9ac level. These changes of histone modification may serve as early epigenetic biomarkers for TCA exposure and the related diseases, offering the safe environmental exposure concentration reference.

摘要

三氯乙酸 (TCA) 是饮用水氯化消毒的常见非挥发性副产物。有必要了解表观遗传毒性和建立环境 TCA 暴露安全暴露限值的机制。本研究探讨了 TCA 处理的人肝细胞 L-02 在不同时间和浓度下的组蛋白修饰变化。TCA（0.1 mM、0.3 mM和0.9 mM）对L-02细胞的生长有抑制作用，形态没有明显变化。用 TCA 处理 24 小时和 48 小时，L-02 细胞显示组蛋白脱乙酰酶 (HDAC) 的 mRNA 和蛋白质水平降低，但在 72 小时后增加。TCA暴露早期HDACs的下调可能是H3K9ac水平升高的重要原因之一。