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 enhances hepatocarcinogenesis in the rat. In the present study, we examined the time course of hepatocarcinogenesis induced by diethylnitrosamine (DEN) after cessation of alcohol using numbers and areas of glutathione S transferase placental form (GST-P)-positive foci and the activity of ornithine decarboxylase (ODC) in males of the Wistar strain. Fifty six rats 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, and then eight rats were killed. The remaining rats were divided into 6 groups. Three alcohol cessation groups were maintained on control liquid diet (C diet) instead of Al diet for 3, 6 and 12 weeks, respectively. The others, as reference groups were maintained on the Al diet continuously for the same periods, respectively. The numbers of GST-P-positive foci per unit area of the liver were not markedly changed after cessation of alcohol. However, their areas were increased with time, so that values in the alcohol cessation groups at 3 and 12 weeks were significantly higher than those in the reference groups at the same points, respectively. Furthermore, ODC activity was significantly elevated in the alcohol cessation groups at 3 and 6 weeks compared to reference groups, but not at 12 weeks when reduction was rather observed. These results suggest that cessation of long-term alcohol administration enhances hepatocarcinogenesis and this effect may be closely related to activation of cell proliferation due to the interruption of alcohol insult.
Tanaka
Takashi
T
Department of Public Health, Osaka City University Medical School, Osaka, 545-8585 Japan. takabon@med.osaka-cu.ac.jp
Hirota
Yoshio
Y
Kuriyama
Maki
M
Nishiguchi
Shuhei
S
Otani
Shuzo
S