|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1997 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1996 : ¥1,000,000 (Direct Cost : ¥1,000,000)
It has been reported that the occurence of hepatocellularcarcinoma is higher in heavy drinkers. To investigate the effect of a adminstration of alcohol on hepatocarcinogenesis, some patterns of administration of alcohol were examined for modifying on diethylnitrosamine-induced neoplasia of liver in male Wistar rats using the mediun-term bioassay system of hepatocarcinogenesis of Ito. Carcinogenuic potential was scored by the number and area per cm^2 of induced glutathione S-transferase placental form (GST-P) -positive foci in the liver. And ornithine decarboxylaze (ODC) activity was mesured as another carcinogenic potential and the parameter of cell proliferation.
In experiment 1, rats ware given a single i.p.injection of diethylnitrosamine (200 mg/kg) body weight) and maintaind on the ordinary solid diet for 2 weeks. Then rats were devided into five groops : groop 1 maintained on the control diet (C diet) for 24 weeks, groop 2 maintained on the liquid diet containing 5% ethanol (5% Adi
ent) for 12 weeks and later on the Cdiet for 12 weeks instead of 5% Adiet, groop 3 maintained on the Cdiet for 24 weeks, grooop 4 maintained on the cycle of Cdiet for two days for 24 weeks, groop 5 maintained on the 2.5% Adient for 24 weeks. All groops were subjected to partial heratectomy at week 3. In experiment 2, sequential changes in the nummber and area per cm^2 of GST-P positive foci and ODC activity were measured at 0,3,6 and 12 weeks later after withdrawal of alcohol.
In experiment 1, the number and area per cm^2 of GST-P foci were significantly increased in the groop 2. But the ODC activity was not so high in the groop 2. In experiment 2, the nummber per cm^2 of GST-P positic foci was not so changed after withdrowal of alcoho, but area per cm^2 of GST-P foci was increased as weeks after withdrowal of alcohol elapcing. And ODC activity was significantly elevated at 3 weeks and 6 weeks later after withdrowal of alcohol, but its activity at 12 weeks after was reduced as on administin of alcohol.
These results suggested that withdrawal of long-term administration of alcohol have promotinng effect on development of neoplastic noduls and it could be released the suppression of cell proliferation by alcohol. Less