Time-concentration-dependent profile of histone modifications on human hepatocytes treated by trichloroacetic acid.

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.