Lipid peroxidation and formation of 8-hydroxydeoxyguanosine from acute doses of halogenated acetic acids

Chlorinated, brominated, and mixed bromochloro acetates are major by-products of water disinfection by chlorine or ozone. The chlorinated acetates, trichloroacetate (TCA) and dichloroacetate (DCA), are carcinogenic in rodents. Brominated analogs of TCA and DCA have received little study. TCA and DCA induce lipid peroxidation in the livers of rodents when administered acutely. Oxidative stress can also result in oxidative damage to DNA, most commonly measured as increases in 8-hydroxydeoxyguanosine (8-OHdG) adducts. In this study, the ability of acute doses of TCA, DCA, dibromoacetate (DBA), bromodichloroacetate (BDCA), and bromochloroacetate (BCA) to induce lipid peroxidation and 8-OHdG formation was examined. Male B6C3F1 mice developed significant increases in 8-OHdG/dG ratios in nuclear DNA isolated from livers when treated with haloacetates. The extent of 8-OHdG formation appeared to be related to the ability to induce thiobarbituric acid-reactive substances (TEARS). The order of potency was DEA congruent to BCA > BDCA > DCA > TCA. The induction of 8-OHdG was found to be generally more sensitive to treatment with haloacetates than the TEARS response. Significantly elevated levels of 8-OHdG were observed at doses of DEA, BCA, and BDCA as low as 30 mg/kg. We suggest that formation of 8-OHdG by brominated haloacetates may contribute to their toxicological effects. (C) 1996 Society of Toxicology