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OXIDATIVE DNA DAMAGE FROM POTASSIUM BROMATE EXPOSURE IN LONG-EVANS RATS IS NOT ENHANCED BY A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS
Citation:
McDorman, K. S., B. F. Pachkowski, J. Nakamura, D C. Wolf, AND J. A. Swenberg. OXIDATIVE DNA DAMAGE FROM POTASSIUM BROMATE EXPOSURE IN LONG-EVANS RATS IS NOT ENHANCED BY A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS. CHEMICO-BIOLOGICAL INTERACTIONS. Elsevier Ireland Limited, Limerick, Ireland, 152(2-3):107-117, (2005).
Impact/Purpose:
To determine whether exposure to a chemical mixture of DBPs in drinking water resulted in a less than additive carcinogenic response
Description:
Public drinking water treated with chemical disinfectants contains a complex mixture of disinfection by-products (DBPs) for which the relative toxicity of the mixtures needs to be characterized to accurately assess risk. Potassium bromate (KBrO3) is a by-product from ozonation of high-bromide surface water for production of drinking water and is a rodent carcinogen that produces thyroid, mesothelial, and renal tumors. The proposed mechanism of KBrO3 renal carcinogenesis involves the formation of 8-oxoguanine (8oxoG), a promutagenic base lesion in DNA typically removed through base excision repair (BER). In this study, male Long-Evans rats were exposed via drinking water to carcinogenic concentrations of KBrO3 (0.4 g/L), 3-chloro-4-(dichloromethyl)-5-hydroxy2(5H)-furanone (0.07 g/L), chloroform (1.8 g/L), bromodichloromethane (0.7 g/L), or a mixture of all these chemicals for 3 weeks. Half of one kidney was processed for microscopic examination, and the remaining kidney was frozen for isolation of genomic DNA. Levels of 8oxoG were measured using HPLC with electrochemical detection in DNA samples incubated with formamidopyrimidine-DNA glycosylase. Aldehydic lesions (e.g., abasic sites) in DNA samples were quantitated using an aldehyde-reactive probe slot-blot assay. Treatment with KBrO3 produced a measurable increase of 8oxoG in the kidney, and this effect was greater than that produced by treatment with the DBP mixture. No other single chemical treatment caused measurable increases of 8oxoG. The mixture effect on the amount of 8-oxoG observed in this study suggests an interaction between chemicals that reduced the generation of oxidative DNA damage. No increases in abasic sites were observed with treatment, but a decrease was apparent in the rats treated with the DBP mixture. These data are consistent with our previous studies where exposure to this chemical mixture resulted in a less than additive carcinogenic response.