HEPATOCYTE GROWTH-FACTOR ENHANCEMENT OF PRENEOPLASTIC HEPATIC FOCI DEVELOPMENT IN RATS TREATED WITH DIETHYLNITROSAMINE AND N-ETHYL-N-HYDROXYETHYLNITROSAMINE

Effects of hepatocyte growth factor were investigated in a two-stage r at liver carcinogenesis protocol. Male F344 rats were first treated wi th diethylnitrosamine (200 mg/kg, i.p.) and then, starting two weeks l ater, with N-ethyl-N-hydroHyethylnitrosamine (EHEN) for 6 weeks at a d ose of 0.01% in drinking water. Hepatocyte growth factor, which was in jected i.v. at a dose of 200 mu g/kg body weight one (at week 3) or tw o times (at weeks 3 and 4) during EHEN administration, significantly i ncreased the development of preneoplastic glutathione S-transferase pl acental form-positive foci. Although the observed effects of hepatocyt e growth factor were weaker than that of the two-thirds partial hepate ctomy (PH) performed at week 3, the present results suggest that the e nhancing effects of PH performed during the promotion stage may be lar gely mediated through induction of hepatocyte growth factor.