REAPPRAISAL OF 8 REPRESENTATIVE CARCINOGENIC AND NONCARCINOGENIC COMPOUNDS IN A NEW MEDIUM-TERM RAT-LIVER BIOASSAY USING D-GALACTOSAMINE

The carcinogenic potential of eight different compounds was assayed in a new medium-term carcinogenicity bioassay using D-galactosamine (DGA ) as a non-surgical method to induce regeneration in place of partial hepatectomy (PH). Male rats were initially given a single i.p. injecti on (200 mg/kg) of diethylnitrosamine (DEN) and after 2 weeks on basal diet, received two i.p. injections of DGA (300 mg/kg) at the end of we eks 2 and 5. They were treated with one of the test compounds aflatoxi n B-1, benzo[a]pyrene, diethylstilbestrol, urethane, sodium saccharin, bucetin, D-mannitol and sodium chloride in the diet or basal diet alo ne for weeks 3-8. Carcinogenic potential was assessed by comparing the numbers and areas per cm(2) of glutathione S-transferase placental fo rm-positive (GST-P+) foci in the livers of treated animals with those of the control animals given DEN/DGA alone. Positive estimations of ca rcinogenicity were obtained for the hepatocarcinogens anatoxin B-1, di ethylstilbestrol or urethane, and for the non-liver carcinogen benzo[a ]pyrene. Negative values were shown in rats treated with the non-carci nogens, D-mannitol and sodium chloride. The two other non-liver carcin ogens sodium saccharin and bucetin, also did not exert positive effect s in the system. The present data are consistent with findings in prev ious medium-term bioassays using PH. Our results thus confirm that the present bioassay protocol with repeated administration of DGA instead of PH may offer a new and sensitive non-invasive method to screen lar ge numbers of environmental carcinogens.