Enhancing effects of phenobarbital and 3-methylcholanthrene on GST-P-positive liver cell foci development in a new medium-term rat liver bioassay using D-galactosamine.

Abstract

The carcinogenic potential of phenobarbital (PB) and 3-methylcholanthrene (3-MC) was assayed in a new medium-term carcinogenicity bioassay using D-galactosamine (DGA) as a nonsurgical method to induce liver cell regeneration in place of partial hepatectomy (PH). Rats were initially given a single ip injection (200 mg/kg) of diethylnitrosamine (DEN) and after 2 wk on basal diet received 2 ip injections of DGA (300 mg/kg) at the end of wk 2 and 5. They were treated with one of the test compounds PB or 3-MC in the diet or fed basal diet for wk 3-8 Carcinogenic potential was assessed by comparing the numbers and areas per square centimeter of glutathione S-transferase placental form-positive (GST-P+) foci in the livers of test chemical-treated animals with those of the control animals given DEN/DGA alone. Positive estimations of carcinogenicity were obtained for PB, which is a nongenotoxic liver tumor promoter, and for 3-MC, which is a genotoxic nonliver carcinogen. Increases of liver/body weight ratios and serum total cholesterol were observed in rats treated with PB or 3-MC. Interestingly, interlobe differences were found on the development of GST-P+ liver cell foci. Our results thus confirm that the present bioassay protocol with repeated administration of DGA instead of PH may offer a new and sensitive method to screen large-numbers of environmental liver and nonliver carcinogens.