Inhibition by N-(4-hydroxyphenyl) retinamide of exogenous and endogenous liver carcinogenesis in rats

The effects of N-(4-hydroxyphenyl)retinamide (4-HPR) on diethylnitrosamine (DEN)-initiated exogenous and a choline-deficient, L-amino acid-defined (CDAA) diet-associated endogenous rat liver carcinogenesis were studied. In the exogenous model, male Fischer 344 rats, 6 weeks old, were given 200 mg/kg body weight of DEN, partially hepatectomized on Week 3, and administered 4-HPR at doses of 0, 0.04, 0.08 and 0.16% between Weeks 2 and 8. In the endogenous model, rats were fed the CDAA diet containing 4-HPR for 12 weeks. 4-HPR inhibited development of glutathione S-transferase placental form (GST-P)-positive foci in both models, more prominent in the latter case. 4-HPR also inhibited the induction of hepatocyte necrosis and connective tissue increase caused by the CDAA diet. It is thus indicated for 4-HPR to exert chemopreventive effects against exogenous and endogenous rat liver carcinogenesis.