Haloacetonitriles Induce Structure-Related Cellular Toxicity Through Distinct Proteome Thiol Reaction Mechanisms.

ABSTRACT: Haloacetonitriles (HANs) are a class of toxic drinking water disinfection byproducts (DBPs). However, the toxicity mechanisms of HANs remain unclear. We herein investigated the structure-related in vitro toxicity of 6 representative HANs by utilizing complementary bioanalytical approaches. Dibromoacetonitrile (DBAN) displayed strong cytotoxicity and Nrf2 oxidative stress responses, followed by monohalogenated HANs (monoHANs) while other polyhalogenated HANs (polyHANs) exhibited little toxicity. Activity based protein profiling (ABPP) revealed that toxic HANs adduct to human proteome thiols, supporting thiol reactivity as the primary toxicity mechanism for HANs. By using glutathione (GSH) as a thiol surrogate, monoHANs reacted with GSH via S_N2 while polyHANs reacted through ultra

SUBMITTER: Yeung K 

PROVIDER: S-EPMC11741059 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature