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

The carcinogenic potential of phenobarbital (PBI and 3-methylcholanthr ene (3-MC) was assayed in a new medium-term carcinogenicity bioassay u sing D-galactosamine (DGA) as a nonsurgical method to induce liver cel l regeneration in place of partial hepatectomy (PH). Rats were initial ly 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 c ompounds PB or 3-MC in the diet or fed basal diet for wk 3-8. Carcinog enic potential was assessed by comparing the numbers and areas per squ are centimeter of glutathione S-transferase placental form-positive (G ST-P+)) foci in the livers of test chemical-treated animals with those of the control animals given DEN/DGA alone. Positive estimations of c arcinogenicity were obtained for PB, which is a nongenotoxic liver tum or promoter, and for 3-MC, which is a genotoxic nonliver carcinogen. I ncreases of liver/body weight ratios and serum total cholesterol were observed in rats treated with PB or 3-MC. Interestingly, interlobe dif ferences 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 meth od to screen large numbers of environmental liver and nonliver carcino gens.