Rat liver in vivo replicative DNA synthesis test for short-term predictionof nongenotoxic (Ames-negative) hepatocarcinogenicity: a collaborative study of the Nongenotoxic Carcinogen Study Group of Japan

A collaborative study was conducted to evaluate whether a replicative DNA s ynthesis (RDS) test using the rat liver can detect nongenotoxic (Ames-negat ive) hepatocarcinogens with three or seven daily administrations at dose-le vels effective in long-term bioassays. The assay methods were well-validate d by the 14 participants. Of six compounds tested, carbon tetrachloride (50 and 100 mg/kg), clofibrate (125 and 250 mg/kg), diethylstilbestrol (0.125 and 0.25 mg/kg) and urethane (100 mg/kg) gave positive results, methyl carb amate (200 and 400 mg/kg) exerted equivocal effects, and D,L-ethionine (125 mg/kg) failed to elevate RDS. These findings suggest that the RDS test can detect many nongenotoxic rat hepatocarcinogens with short-term administrat ion at dose-levels used in long-term bioassays. (C) 1999 Elsevier Science I reland Ltd. All rights reserved.