Distinct cytotoxicity of water disinfection byproducts in human uroepithelium and Chinese hamster ovary cells.

Water disinfection unintentionally produces hundreds of disinfection byproducts (DBPs). Although the cytotoxicity of over 100 DBPs has been extensively studied in Chinese hamster ovary (CHO) cells, toxicity data in human cell models remain limited. Given the epidemiological association of DBPs with bladder cancer risk, it is necessary to conduct studies using cell lines that exhibit biological characteristics resembling human bladder cells, e.g., the immortalized human uroepithelium SV-HUC-1 cells. In this study, the cytotoxicity of 14 regulated and unregulated DBPs in SV-HUC-1 and CHO-K1 cells was examined in parallel using a real-time cell analysis (RTCA) platform. SV-HUC-1 cells exhibited greater sensitivity to eight DBPs than CHO-K1 cells. Notably, iodoacetic acid (IAA) and bromoacetic acid (BAA) were significantly more cytotoxic to SV-HUC-1 cells than iodoacetonitrile (IAN) and bromoacetonitrile (BAN), whereas the reverse trend was observed in CHO-K1 cells. Cell cycle analysis showed that only IAN and BAN induced G2/M phase arrest in SV-HUC-1 cells. In contrast, in CHO-K1 cells, IAN caused G2/M arrest, BAN and CAN induced G0/G1 arrest, and IAA and BAA arrested cells in the S phase. Morphological assessments showed that SV-HUC-1 cells aggregated upon exposure to monohaloacetic acids (monoHAAs), while exposure to monohaloacetonitriles (monoHANs) led to cell shrinkage and nuclear lysis. CHO-K1 cells maintained a spindle-shaped morphology with reduced size under monoHAA exposure, whereas monoHAN treatment induced an elliptical shape, with a notable subset transitioning to hypertrophic hyperploidy. These findings highlight cell- and DBP-specific toxic effects, stressing the need to include human cell lines in future DBP toxicity assessments.