In this study we examined the ability of peroxisome proliferators to induce oxidative DNA damage in the form of 8-hydroxydeoxyguanosine (OHdG). We studied the hypolipidemic drug ciprofibrate, which is among the most potent and efficacious of the peroxisome proliferators, and perfluorodecanoic acid (PFDA), which is an inhibitor of peroxisomal β-oxidation. Rats were fed 0.01% ciprofibrate in the diet, or were injected with PFDA at doses of 3 or 10 mg/kg every 14 days (controls and ciprofibrate-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 nucleosides, and the levels of OHdG as well as normal nucleosides were analysed by high-performance liquid chromatography with electrochemical detection. Ciprofibrate increased OHdG concentrations at all times except for the initial 10-day timepoint. Both doses of PFDA increased OHdG levels at all times except the last timepoint, at which only the higher dose produced a significant increase. This study shows that both ciprofibrate and PFDA induce oxidative DNA damage in the form of OHdG. Furthermore, the inhibition of peroxisomal β-oxidation by PFDA does not affect the development of OHdG.
|Number of pages||6|
|State||Published - Dec 9 1994|
Bibliographical noteFunding Information:
This research was supported by National Institutes of Health grants CA43719 and CA01688, and by the Kentucky Agricultural Experiment Station.
- Oxidative damage
ASJC Scopus subject areas
- Cancer Research