Methanethiol is a widely existing malodorous
pollutant with health effects on the human population. However, the cytotoxicity mechanism of
methanethiol in vitro and its metabolic transformation (bioactivation or detoxification) have not been fully elucidated. Herein, the metabolites of
methanethiol during cell culture and the cytotoxicity of
methanethiol in human bronchial epithelial (16HBE) cells were investigated. Results indicate that
methanethiol (10-50 μM) was partially converted into
dimethyl sulfide, mainly catalyzed by
thiol S-methyltransferase in the 16HBE cells, and then it induced potent cytotoxicity and cell membrane permeability. Moreover,
methanethiol induced intracellular
reactive oxygen species (ROS) up to 50 μM and further activated the
tumor necrosis factor (TNF) signaling pathway, which eventually led to the decline in the mitochondrial membrane potential (
MMP) and cell
necrosis. However, all these effects were significantly alleviated with gene silencing of the
methyltransferase-like
protein 7B (METTL7B). These results indicate that
methanethiol may induce cell
necrosis in human respiratory tract cells mainly mediated by S-
methyltransferase with interfering TNF and ROS induction. Non-target metabolomics results suggest that
methanethiol potently affects expression of endogenous small molecule metabolites in 16HBE cells. To some extent, this work shows the possible conversion path and potential injury mechanism of human respiratory tract cells exposed to
methanethiol.