Investigation of nuclear enzyme topoisomerase as a putative molecular target of monohaloacetonitrile disinfection by-products

Abstract

Disinfection by-products occur widely as the unintended effect of water disinfection and are associated with toxicity and adverse human health effects. Yet the molecular mechanisms of their toxicity are not well understood. To investigate the molecular basis of hyperploidy induction by monohaloacetonitriles, the interaction of monohaloacetonitriles with topoisomerase II in Chinese hamster ovary cells was examined. We showed a concentration-dependent inhibition of DNA decatenation activity of topoisomerase under acellular conditions while in vitro monohaloacetonitrile treatment expressed mixed results. The working hypothesis, that topoisomerase II is a molecular target of monohaloacetonitriles, was only partially supported. Nevertheless, this research serves as a starting point toward molecular mechanisms of toxic action of monohaloacetonitriles.