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Methyl triclosan (mTCS) is a methylated derivative of triclosan (TCS), which is extensively used as an antimicrobial component of various nursing products and disinfectants. Current research studies of mTCS mainly focused on the environmental persistence and bioaccumulation potential. Knowledge regarding the toxicity and carcinogenicity of mTCS is limited until now. In this study, the human hepatocyte L02 cells were used to investigate the cellular effects of mTCS under different concentrations (0.1-60 μM). The hormesis effect was observed where a low dose of mTCS (≤5 μM) exposure stimulated the cell proliferation ability, while high-dose exposure (≥20 μM) inhibited cell proliferation. In the same time, low doses of mTCS (0.5 and 1 μM) induced enhanced anchorage-independent proliferation ability and cell migration ability, indicating a positive effect on malignant transformation in L02 cells. Moreover, reactive oxygen species productions were significantly increased after mTCS exposure (≥1 μM), as compared with the control group. Furthermore, expressions of tumor-related genes, mouse double minute 2 (MDM2), matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA), and proto-oncogene MYC (c-Myc), Jun, and FosB were significantly upregulated, while no significant changes were observed on expressions of apoptosis-related and cell cycle-related genes in L02 cells after exposure of low-dose mTCS. In conclusion, these results indicated that a low dose of mTCS had a hormesis effect in L02 cells on cell proliferation and malignant transformation in vitro, which might be mediated through oxidative stress response.

Triclosan (TCS) has been a widely used antibacterial agent in medical and personal care products in the last few decades. Methyl TCS (MTCS) is the major biotransformation product of TCS through replacement of the hydroxyl group with methoxy. Previous studies revealed that MTCS showed reduced toxicity but enhanced environmental persistence, when compared with TCS. Till date, the toxicological molecular mechanisms of TCS and MTCS remain to be clarified. This study aimed to investigate the transcriptomic changes in HepG2 cells induced by TCS and MTCS using microarray chips and to identify key target genes and related signal pathways. The microarray data showed that there were 1664 and 7144 differentially expressed genes (DEGs) in TCS- and MTCS-treated groups, respectively. Gene ontology (GO) enrichment and Kyoto Encyclopedia of genes and genomes (KEGG) analysis revealed that TCS and MTCS induced overlapping as well as distinct transcriptome signatures in HepG2 cells. Both TCS and MTCS could result in various biological responses in HepG2 cells mainly responding to biosynthetic and metabolic processes but probably through different regulatory pathways. Among the selected 50 GO terms, 9 GO terms belonging to the cellular component category were only enriched in the MTCS group, which are mainly participating in the regulation of cellular organelle's function. KEGG analysis showed that 19 and 59 pathway terms were separately enriched in TCS and MTCS groups, with only seven identical pathways. The selected 10 TCS-specific signal pathways are mainly involved in cell proliferation and apoptosis, while the selected 10 MTCS-specific pathways mainly take part in the regulation of protein synthesis and modification. The overall data suggested that MTCS induced more enriched DEGs, GO terms, and pathway terms than TCS. In conclusion, compared with TCS, MTCS presents lower polarity and stronger lipophilicity, enabling MTCS to cause more extensive transcriptomic changes in HepG2 cells, activate differentiated signal pathways, and finally lead to differences in biological responses.