Increased 8-hydroxydeoxyguanosine in hepatic DNA of rats treated with the peroxisome proliferators ciprofibrate and perfluorodecanoic acid.
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 beta-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 beta-oxidation by PFDA does not affect the development of OHdG.
Huang
C Y
CY
University of Kentucky, Department of Nutrition and Food Science, Lexington, 40506-0054.
Wilson
M W
MW
Lay
L T
LT
Chow
C K
CK
Robertson
L W
LW
Glauert
H P
HP
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D003652:Decanoic Acids / Q000494:pharmacology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D058607:Fibric Acids; D005466:Fluorocarbons / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D003652:Decanoic Acids; D058607:Fibric Acids; D005466:Fluorocarbons; C036567:perfluorodecanoic acid; D002995:Clofibric Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C019304:ciprofibrate; D003849:Deoxyguanosine