RISK EVALUATION OF ACETAMINOPHEN IN PRE-EXISTING FATTY LIVER INDUCED BY CHOLINE-DEVOID DIET ON LIVER CARCINOGENESIS IN MALE F344 RATS

Abstract

The initiating potential of acetaminophen (APAP) was investigated in prexisting fatty liver induced by choline-devoid (CD) diet in male F344 rats. APAP was intragastrically administered at the single necrogenic doses, 0.5g/kg, 1.0g/kg, 1.5g/kg body weight, Diethylnitrosamine (DEN) at 20mg/kg body weight was intraperitoneally injected after 4 weeks feeding of CD or choline-supplemented diet. In the CD treated animals, DEN significantly increased the number and area of both glutathione Stransferase placental form (GST-P) and γ-glutamyl transferase (GGT) -positive foci and nodules but APAP did not enhance at all. These results indicate that APAP does not possess significant initiating activity in damaged liver of rats.