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

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.

KEYWORDS:

• Trichloroacetic acid
• HDACs
• PCAF
• H3K9ac

Disclosure statement

No potential conflicts of interest was reported by authors.

Data availability statement

The data that support the findings of this study are available from the corresponding authors upon request.

Additional information

Funding

This work was supported by the Natural Science Foundation of Guangdong Province of China [2021A1515011220]; Administration of Traditional Chinese Medicine of Guangdong Province of China [20211008]; National Natural Science Foundation of China [81473014]; Open Fund of State Key Laboratory of Respiratory Disease of China [SKLRD-OP-201810]; Top Young Talents of Guangdong Hundreds of Millions of Projects of China [87316004] and Outstanding Young Scholar of Double Hundred Talents and Scientific Research Creativeness Cultivation Project for Outstanding Postgraduates of Jinan University of China.