Trichloroacetic acid effects on rat liver peroxisomes and enzyme-altered foci.

Abstract

The initiating and promoting effects of trichloroacetic acid (TCA) were investigated using a rat hepatic enzyme-altered foci bioassay. The experimental protocol used has been shown to induce gamma-glutamyltranspeptidase (GGT)-positive foci in hepatic tissue following an initiating dose with a genotoxic carcinogen. Twenty-four hours following 2/3 partial hepatectomy, rats received either a single oral dose (1500 mg/kg) or 5000 ppm TCA in drinking water for 10, 20, or 30 days. Two weeks after the end of TCA exposure, the rats were promoted for 3 or 6 months with 500 ppm phenobarbital in drinking water. TCA failed to induce GGT-positive foci using this initiation protocol. In addition, groups of 2/3 partially hepatectomized rats were initiated with a single oral dose of diethylnitrosamine (10 mg/kg) and then administered 50, 500, or 5000 ppm TCA drinking water. In this promotion protocol, TCA exposure resulted in a significant increase in the number of GGT-positive foci. The ability of TCA to stimulate peroxisomal-dependent palmitoyl-coenzyme A oxidation was also investigated. Only the 5000 ppm TCA treatment within the promotion protocol resulted in a significant, although minor, stimulation of peroxisomal enzyme activity. The findings support the hypothesis that TCA may possess weak promoting activity in the rat liver.