© 1996 Oxford University Press
research-article |
Lipid Peroxidation and Formation of 8-Hydroxydeoxyguanosine from Acute Doses of Halogenated Acetic Acids
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*Pharmacology/Toxicology Graduate Program, Washington State University Pullman, Washington 99164
The Raabe College of Pharmacy, Ohio Northern University Ada, Ohio 45810
Battelle Pacific Northwest National Laboratory, Health Risk Assessment Department MSIN: P7-56, Richland, Washington 99352
Received June 27, 1995; accepted December 8, 1995
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 thiobarbi-turic acid-reactive substances (TBARS). The order of potency was DBA 
BCA > BDCA > DCA > TCA. The induction of 8-OHdG was found to be generally more sensitive to treatment with haloacetates than the TBARS response. Significantly elevated levels of 8-OHdG were observed at doses of DBA, 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.