Effect of the peroxisome proliferators ciprofibrate and perfluorodecanoic acid on hepatic cell proliferation and toxicity in sprague-dawley rats

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

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The objective of this study was to compare the effects of perfluorodecanoic acid (PFDA) and ciprofibrate on the induction of hepatic toxicity and on hepatocellular proliferation in rats. In the first study, rats were first subjected to partial hepatectomy and then injected with [3H]thymidine (20 μCi/injection) at 23, 24, 25, 47, 48 and 49 h afterwards. After a 2 week recovery period, rats were injected with one of four levels of PFDA (03, 1.0, 3.0 or 10 mg/kg/injection) in four i.p. doses every 14 days, or were fed 0.01% or 0.003% ciprofibrate. Six days after the last PFDA injection and three days before the animals were killed, an osmotic minipump containing 20 mg/ml 5-bromo-2'-deoxyuridine (BrdU) was implanted s.c for the measurement of DNA synthesis. Peroxisomal fatty acyl-CoA oxidase activity was significantly enhanced in both PFDA and ciprofibrate-treated groups in a dose-dependent manner. Hepatotoxicity, measured as the loss of [3H]thymldine from hepatic DNA, was not significantly affected by any of the treatments. Hepatic DNA synthesis was significantly increased only in rats receiving the highest dose of PFDA. In order to determine the time course of ciprofibrate- and PFDA-induced cell proliferation, we conducted another study with more time points. Rats were fed 0.01% ciprofibrate or were injected every 14 days with 3 or 10 mg PFDA/kg body weight for 10 days, 24 days, 6 weeks, 26 weeks or 54 weeks. Cell proliferation was quantified as in the first study. Ciprofibrate increased cell proliferation at the early but not the later time points, whereas PFDA increased cell proliferation at most times throughout the study. This study demonstrates that PFDA and ciprofibrate do not selectively induce hepatic toxicity and that their effects on cell proliferation do not correlate with their carcinogenic or promoting activities.

Original languageEnglish
Pages (from-to)2847-2850
Number of pages4
JournalCarcinogenesis
Volume15
Issue number12
DOIs
StatePublished - Dec 1994

Bibliographical note

Funding Information:
We thank Robert Stringfield for help with the immunohistochemical staining procedure, and Dr Michael Schwarz for helpful discussions. This study was supported by grants CA43719 and CA01688 from the National Cancer Institute, and by the Kentucky Agricultural Experiment Station (KAES journal article number 92-9-76).

ASJC Scopus subject areas

  • Cancer Research

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