INCREASED 8-HYDROXYDEOXYGUANOSINE IN HEPATIC DNA OF RATS TREATED WITHTHE PEROXISOME PROLIFERATORS CIPROFIBRATE AND PERFLUORODECANOIC ACID

In this study we examined the ability of peroxisome proliferators to i nduce oxidative DNA damage in the form of 8-hydroxydeoxyguanosine (OHd G), We studied the hypolipidemic drug ciprofibrate, which is among the most potent and efficacious of the peroxisome proliferators, and perf luorodecanoic acid (PFDA), which is an inhibitor of peroxisomal beta-o xidation. Rats were fed 0.01% ciprofibrate in the diet, or were inject ed with PFDA at doses of 3 or 10 mg/kg every 14 days (controls and cip rofibrate-fed rats were given equivalent doses of corn oil). Rats were maintained for 10 days, 24 days, 6 weeks, 26 weeks, or 54 weeks. DNA was isolated from the liver at these times and hydrolysed to nucleosid es, and the levels of OHdG as well as normal nucleosides were analysed by high-performance liquid chromatography with electrochemical detect ion. Ciprofibrate increased OHdG concentrations at all times except fo r the initial 10-day timepoint. Both doses of PFDA increased OHdG leve ls at all times except the last timepoint, at which only the higher do se produced a significant increase. This study shows that both ciprofi brate and PFDA induce oxidative DNA damage in the form of OHdG. Furthe rmore, the inhibition of peroxisomal beta-oxidation by PFDA does not a ffect the development of OHdG.