Modulation of the cytotoxicity and genotoxicity of the drinking water disinfection byproduct lodoacetic acid by suppressors of oxidative stress.
Drinking water disinfection byproducts (DBPs) are generated by the chemical disinfection of water and may pose a hazard to the public health. Previously we demonstrated that iodoacetic acid was the most cytotoxic and genotoxic DBP analyzed in a mammalian cell system. Little is known of the mechanisms of its genotoxicity. The involvement of oxidative stress in the toxicity of iodoacetic acid was analyzed with the antioxidants catalase and butylated hydroxyanisole (BHA). lodoacetic acid toxicity was quantitatively measured with and without antioxidants in Salmonella typhimurium strain TA100 and with Chinese hamster ovary (CHO) cells. The endpoints included cytotoxicity in S. typhimurium or in CHO cells, mutagenicity in S. typhimurium, and genotoxicity in CHO cells. Neither catalase nor BHA reduced the level of iodoacetic acid induced cytotoxicity in S. typhimurium. In CHO cells neither antioxidant caused a significant reduction in iodoacetic acid induced cytotoxicity. However, in S. typhimurium, BHA or catalase reduced the mutagenicity of iodoacetic acid by 33.5 and 26.8%, respectively. Likewise, BHA or catalase reduced iodoacetic acid induced genomic DNA damage by 86.5 and 42%, respectively. These results support the hypothesis that oxidative stress is involved in the induction of genotoxicity and mutagenicity by iodoacetic acid.
Cemeli
Eduardo
E
Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
Wagner
Elizabeth D
ED
Anderson
Diana
D
Richardson
Susan D
SD
Plewa
Michael J
MJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004249:DNA Damage; D004202:Disinfectants / Q000378:metabolism*; D005260:Female; D019807:Iodoacetic Acid / Q000032:analysis / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity; D010053:Ovary / Q000166:cytology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000502:physiology; D014881:Water Supply / Q000032:analysis*
D000975:Antioxidants; D004202:Disinfectants; D009153:Mutagens; D002083:Butylated Hydroxyanisole; D002374:Catalase; D019807:Iodoacetic Acid