Increased 8-hydroxydeoxyguanosine in hepatic DNA of rats treated with the peroxisome proliferators ciprofibrate and perfluorodecanoic acid

Cheng yu Huang, Mary W. Wilson, L. Travis Lay, Ching K. Chow, Larry W. Robertson, Howard P. Glauert

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)223-228
Number of pages6
JournalCancer Letters
Volume87
Issue number2
DOIs
StatePublished - Dec 9 1994

Bibliographical note

Funding Information:
This research was supported by National Institutes of Health grants CA43719 and CA01688, and by the Kentucky Agricultural Experiment Station.

Keywords

  • 8-Hydroxydeoxyguanosine
  • Carcinogenesis
  • Oxidative damage
  • Peroxisome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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