Cessation of Long-term Alcohol Administration and Two-day Cycling of Exposure Respectively Promote and Inhibit Hepatocarcinogenesis in Rats


The effects of different patterns of alcohol administration on hepatocarcinogenesis induced by diethylnitrosamine ‍(DEN) in male Wistar rats were assessed using a modified Ito’s medium-term bioassay system. Carcinogenic potential ‍was scored by comparing numbers and areas of glutathione S transferase placental form (GST-P)-positive foci. The ‍activity of ornithine decarboxylase (ODC), the rate-limiting enzyme for polyamine synthesis, was also measured as ‍a parameter of cell proliferation. Rats were given a single i.p. injection of DEN (200 mg/kg body weight), maintained ‍on basal solid diet for two weeks, then divided into five groups: group A maintained on liquid diet in which 36% of ‍total calories were provided by ethanol (diet Al) for 24 weeks; group B maintained on diet Al for 12 weeks and ‍subsequently on control diet (diet C) for 12 weeks; group C maintained on diet C for 24 weeks; group D maintained ‍on a cycle of two days on diet Al followed by two days on diet C; group E maintained on another liquid diet in which ‍18% of total calories were provided by ethanol for 24 weeks. The numbers and areas per cm2 of GST-P positive foci ‍in group B were highest and in group D were the lowest among the five groups. ODC activities in groups A and E ‍were significantly lower than in group C, that for group B was intermediate. These results suggest that the intermittent ‍intake of alcohol exerts preventive potential on hepatocellular lesion development, and that interruption of longterm ‍alcohol administration enhances hepatocarcinogenesis. ‍