Haloacetonitriles (HANs) are a chemical class of disinfection byproducts (DBPs) that form from reactions between disinfectants and dissolved nitrogen precursors, the latter more prevalent in water sources impacted by algae bloom and municipal wastewater effluent discharge. HANs have been shown to be mutagenic, genotoxic, carcinogenic, clastogenic and developmentally toxic. Mammalian cell cycle alteration by HANs was investigated since DNA damage in eukaryotic cells is strongly associated with cell cycle modulation to ensure the integrity of the genome and cell division. Chinese hamster ovary (CHO) cells were treated with monoHANs for 4 h and subsequently incubated in fresh cell culture medium for up to 52 h. All three HANs demonstrated that to be capable of shifting the cell cycle distribution toward high chromosome numbers in a concentration-dependent manner. With 6 �M iodoacetonitrile, 12 �M bromoacetonitrile and 900 �M chloroacetonitrile, no DNA strand breaks were detected after 26 h post-treatment incubation while the cell cycles were exceedingly altered. Cell proliferation of HAN-treated cells was suppressed for as long as 43 to 52 h. Abnormally large cells were observed after 52 h post-treatment incubation without cytotoxicity. The HAN-mediated cell cycle alteration was mitosis- and proliferation-dependent, which suggested that HAN treatment induced mitosis override and further progression of cell cycle resulted in induction of high ploidy cells (8N). Other studies have shown that a transient tetraploid state proceeds to the induction of aneuploidy in cancer cell progression. These data suggest that HAN disruption of the cell cycle and the generation of aberrant cells with abnormal number of chromosomes may contribute to cancer induction and adverse health outcomes associated with consumption of disinfected water. This is the first demonstration of the induction of high ploidy in cells by a class of DBPs.

Cell cycle alterations induced by haloacetonitrile disinfection byproducts

248th National Meeting (2014)

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