Specific epigenetic microenvironment and the regulation of tumor-related gene expression by trichloroethylene in human hepatocytes

Abstract

Trichloroethylene (TCE), an important volatile organic solvent, causes a series of toxic damage to human. Conventional genetic mechanisms cannot fully explain its toxicity and carcinogenicity, indicative of the possible involvement of epigenetic mechanisms. Our study was intended to investigate the epigenetic toxicity and underlying mechanisms of TCE. Data showed that 0.3 mM TCE treatment for 24 h increased the growth of L-02 cells transiently. In contrast, subacute exposure to TCE inhibited cell growth and induced the genomic DNA hypomethylation and histone hyperacetylation. Further studies have revealed the TCE-induced DNA hypomethylation in the promoter regions of tumor-related genes, N-Ras, c-Jun, c-Myc, c-Fos and IGF-II, promoting their protein levels in a time-dependent manner. These results reveal there is a negative relationship existing between DNA hypomethylation and protein expression in tumor-related gene after TCE exposure under specific epigenetic microenvironment, serving as early biomarkers for TCE-associated diseases.

Keywords

• Trichloroethylene
• N-Ras
• C-jun
• C-Myc
• C-Fos
• IGF-II