Role of Histone Modifications and miRNA Regulations in the Toxicity of Trichloroethylene in Terms of Cell Cycle Regulation in Human Kidney Cells

Trichloroethylene (TCE) is an organic solvent with various industrial applications. Therefore, the study aimed to determine the effects of TCE on cytotoxicity, apoptosis, reactive oxygen species (ROS) production, global histone modifications, and regulation in microRNAs (miRNAs) related to cancer pathways in human embryonic kidney cells (HEK-293) after exposure to TCE at concentrations of 0.03, 0.1, and 0.3 mM for 24 h. Results indicated that TCE caused dose- dependent cytotoxicity without induction of significant apoptosis or ROS production at concentrations of ≤ 0.3 mM. Upregulation in myc, pten, and mgmt and downregulation in ctnb1, cd44, and cdkn2a genes involved in cell cycle regulation and proliferation were detected. TCE decreased the expression of the ezh2 gene and increased the expression of riz1 and hat1 genes, which are associated with chromatin-modifying enzymes. Additionally, the levels of H3K27me3, H3K4me3, and H3K9me3 changed significantly. However, the alterations in global levels of H3K9ac were insignificant. TCE significantly altered the expression of approximately 25% of miRNAs related to cancer pathway in the miRNA array panel, as it upregulated 19 miRNAs and downregulated 4 miRNAs of the tested 84 miRNAs. Considering the effects on chromatin modification, proliferation rate, and miRNAs, it can be concluded that these mechanisms may be involved in TCE-induced nephrotoxicity.