No significant paraquat-induced oxidative DNA damage in rats.
The metabolism of paraquat generates oxygen radicals. Paraquat has thus been suggested as a model compound to induce oxidative damage to DNA, lipids and proteins in different cells and tissues, although experimental data are inconsistent. In order to explore the possibilities for an animal model of oxidative DNA damage in vivo, rats were treated with 20 mg/kg paraquat or vehicle i.p. One and five days later we measured DNA oxidation in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in the liver and lung as well as the urinary excretion of 8-oxodG. No significant effects on the level of 8-oxodG in the liver, the lung or the urinary excretion, could be distinguished following paraquat treatment. We found, however, a significant correlation (r = 0.69; p<0.0002) between the 8-oxodG level in the lung and the urinary excretion, but no significant correlation between the level in the liver and the urinary excretion or between the levels in the liver and the lung. During the experiment the rats were clearly affected by the paraquat as they were very lethargic compared to the controls. Accordingly, even at toxic doses, paraquat did not cause detectable oxidative damage to DNA. The data do not support the use of paraquat as a model compound in experiments investigating effects or prevention of oxidative damage to DNA.
Sørensen
M
M
Institute of Public Health, University of Copenhagen, Denmark.
Loft
S
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D004195:Disease Models, Animal; D006540:Herbicides / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010269:Paraquat / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D006540:Herbicides; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D010269:Paraquat