Abstract
Disinfection byproducts (DBPs) are inevitably generated during drinking water disinfection processes, and their hazards have not been well characterized. Because they plausibly cause toxicological and pathological damage to human kidney, we selected the human embryonic kidney (HEK293) cell, instead of the commonly used CHO cell, as a model to investigate the toxic potential and target of 10 DBPs, including 3 haloacetamides, 2 trihaloacetaldehydes and 5 iodomethanes. Based on the chronic toxicity parameter EC10 of the cell viability test, we obtained a toxic rank of the tested DBPs different from previous studies and calculated their risk quotients by combining their actual concentrations in drinking water systems. Then, dichloroacetamide (DCAM), trichloroacetaldehyde (TCAL), and bromochloroiodomethane (BCIM) were selected to conduct multiple mechanistic bioassays, including cellular lactate dehydrogenase (LDH) assay, ATP metabolism, ROS production, mitochondria-derived apoptosis and qRT-PCR assay. All bioassays revealed the effects of interrupting the molecular, physiological and biochemical processes relevant to mitochondrial functions, such as oxidative respiration, apoptosis, and energy metabolism. Our study improved the human risk assessment of DBPs with the help of a convenient model and parameter and revealed that mitochondrion is a potential toxic focus of DBPs exposure at the cellular level.
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