Time Course of Change in Glutathione S-Transferase Positive Foci and Ornithine Decarboxylase Activity after Cessation of Long-term Alcohol Administration in Rats

In our previous experiments, we showed that cessation of long-term alcohol administration enhanceshepatocarcinogenesis in the rat. In the present study, we examined the time course of hepatocarcinogenesis inducedby diethylnitrosamine (DEN) after cessation of alcohol using numbers and areas of glutathione S transferase placentalform (GST-P)-positive foci and the activity of ornithine decarboxylase (ODC) in males of the Wistar strain. Fifty sixrats were given a single i.p. injection of DEN (200 mg/kg body weight), maintained on basal solid diet for two weeks,then maintained on liquid diet in which 36% of total calories were provided by ethanol (Al diet) for 12 weeks, andthen eight rats were killed. The remaining rats were divided into 6 groups. Three alcohol cessation groups weremaintained on control liquid diet (C diet) instead of Al diet for 3 , 6 and 12 weeks, respectively. The others, asreference groups were maintained on the Al diet continuously for the same periods, respectively. The numbers ofGST-P-positive foci per unit area of the liver were not markedly changed after cessation of alcohol. However, theirareas were increased with time, so that values in the alcohol cessation groups at 3 and 12 weeks were significantlyhigher than those in the reference groups at the same points, respectively. Furthermore, ODC activity was significantlyelevated in the alcohol cessation groups at 3 and 6 weeks compared to reference groups, but not at 12 weeks whenreduction was rather observed. These results suggest that cessation of long-term alcohol administration enhanceshepatocarcinogenesis and this effect may be closely related to activation of cell proliferation due to the interruptionof alcohol insult.