EFFECT OF THE PEROXISOME PROLIFERATOR PERFLUORODECANOIC ACID ON THE PROMOTION OF 2-STAGE HEPATOCARCINOGENESIS IN RATS

This study was conducted to determine if the peroxisome proliferator p erfluorodecanoic acid (PFDA) has promoting activity in two-stage hepat ocarcinogenesis. Because PFDA is a non-competitive inhibitor of the pe roxisomal bifunctional enzyme and thus inhibits the peroxisomal beta p athway, we hypothesized that PFDA may not have promoting activity as d o other peroxisome proliferators, because hydrogen peroxide production is inhibited. Twenty-four hours after partial hepatectomy, female Spr ague-Dawley rats were given an initiating dose of 10 mg/kg diethylnitr osamine by gavage. The rats were divided into five groups that receive d 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 h ighest dose of PFDA increased the activity of the peroxisomal enzyme f atty acyl CoA oxidase. PFDA treatment did not increase the tumor incid ence or the number of altered hepatic foci at 9 or 18 months, although the mean volume of foci was increased at 9 months. Ciprofibrate incre ased the incidence of hepatocellular carcinomas at 18 months but did n ot increase the number or volume of altered hepatic foci at 9 or 18 mo nths. Phenobarbital increased the number and volume of foci but did no t influence the tumor incidence. The results of this investigation ind icate that PFDA is not a promoter of hepatocarcinogenesis.