This study was conducted to determine if the peroxisome proliferator perfluorodecanoic acid (PFDA) has promoting activity in two-stage hepatocarcinogenesis. Because PFDA is a non-competitive inhibitor of the peroxisomal bifunctional enzyme and thus inhibits the peroxisomal β pathway, we hypothesized that PFDA may not have promoting activity as do other peroxisome proliferators, because hydrogen peroxide production is inhibited. Twenty-four hours after partial hepatectomy, female Sprague-Dawley rats were given an initiating dose of 10 mg/kg diethylnitrosamine by gavage. The rats were divided into five groups that received monthly i.p. injections of 0.0, 0.05, 0.50 or 5.0 mg/kg PFDA in corn oil or were placed on diets that contained either 0.01% ciprofibrate or 0.05% phenobarbital for 9 or 18 months. Both ciprofibrate and the highest dose of PFDA increased the activity of the peroxisomal enzyme fatty acyl CoA oxidase. PFDA treatment did not increase the tumor incidence or the number of altered hepatic foci at 9 or 18 months, although the mean volume of foci was increased at 9 months. Ciprofibrate increased the incidence of hepatocellular carcinomas at 18 months but did not increase the number or volume of altered hepatic foci at 9 or 18 months. Phenobarbital increased the number and volume of foci but did not influence the tumor incidence. The results of this investigation indicate that PFDA is not a promoter of hepatocarcinogenesis.
|Number of pages||10|
|State||Published - Aug 16 1993|
Bibliographical noteFunding Information:
We thank Travis Lay, Suseela Srinivasan, Patrick Comer and Hui Chen for technical assistance. This research was supported by National Cancer Institute grants CA43719, CA01688, CA07175 and CA22484, and National Institute of General Medical Sciences grant GM41 131. T. Borges was supported by a training grant from the National Institute of Environmental Health Sciences( ES07266). Kentucky Agricultural Experiment Station journal article number 91-9-201.
- altered hepatic foci
- gamma-glutamyl transpeptidase
- perfluorodecanoic acid (PFDA)
ASJC Scopus subject areas
- Cancer Research