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Triclosan (TCS) is used as an antimicrobial agent and has been widely dispersed and detected in the environment and organisms including human samples. Methyl-triclosan (MTCS) is the predominant bacterial TCS metabolite. At present, the toxicological effects and mechanism of TCS and MTCS are still not fully understood. In this study, the cytotoxic effects of TCS and MTCS in HepG2 cells were investigated in terms of cell proliferation, comet assay, cell cycle, and apoptosis. In addition, the expressions of related proteins were detected with western blotting analysis. The results showed that TCS could significantly inhibit cell proliferation, while MTCS had no obvious effect on cell growth. Both TCS and MTCS caused oxidative injury associated with HO-1 induction and increased DNA strand breaks, which consequently initiated the damage repair process via up-regulation of DNA-PKcs. In addition, TCS blocked the HepG2 cells in S and G2/M phases of cell cycle through down-regulation of cyclin A2 and CDK; while MTCS induced cell cycle arrest at the S phase through up-regulation of cyclin A2 and CDK. Furthermore, TCS activated p53 mediated apoptosis in HepG2 cells in a caspase-independent manner, while MTCS induced apoptosis was dependent on caspase. Moreover, TCS exposure exhibited more severe toxicity in HepG2 cells as compared with MTCS exposure, indicating that the replacement of the ionizable proton in TCS by the methyl group in MTCS is correlated with the cellular toxicity and the molecular mechanism. [ABSTRACT FROM AUTHOR]

Triclosan (TCS) is used as an antimicrobial agent and has been widely dispersed and detected in the environment and organisms including human samples. Methyl-triclosan (MTCS) is the predominant bacterial TCS metabolite. At present, the toxicological effects and mechanism of TCS and MTCS are still not fully understood. In this study, the cytotoxic effects of TCS and MTCS in HepG2 cells were investigated in terms of cell proliferation, comet assay, cell cycle, and apoptosis. In addition, the expressions of related proteins were detected with western blotting analysis. The results showed that TCS could significantly inhibit cell proliferation, while MTCS had no obvious effect on cell growth. Both TCS and MTCS caused oxidative injury associated with HO-1 induction and increased DNA strand breaks, which consequently initiated the damage repair process via up-regulation of DNA-PKcs. In addition, TCS blocked the HepG2 cells in S and G2/M phases of cell cycle through down-regulation of cyclin A2 and CDK; while MTCS induced cell cycle arrest at the S phase through up-regulation of cyclin A2 and CDK. Furthermore, TCS activated p53 mediated apoptosis in HepG2 cells in a caspase-independent manner, while MTCS induced apoptosis was dependent on caspase. Moreover, TCS exposure exhibited more severe toxicity in HepG2 cells as compared with MTCS exposure, indicating that the replacement of the ionizable proton in TCS by the methyl group in MTCS is correlated with the cellular toxicity and the molecular mechanism.