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 dichioroacetate (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 (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.
Austin
E W
EW
Pharmacology/Toxicology Graduate Program, Washington State University, Pullman, Washington 99164, USA.
Parrish
J M
JM
Kinder
D H
DH
Bull
R J
RJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000085:Acetates / Q000633:toxicity*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D018736:DNA Adducts / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004563:Electrochemistry; D006219:Halogens; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013056:Spectrophotometry, Ultraviolet; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000085:Acetates; D018736:DNA Adducts; D006219:Halogens; D017392:Thiobarbituric Acid Reactive Substances; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine