The Effect of alcohol on the cemical hepatocarcinogenesis

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08670450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Public health/Health science
• Research Institution: OSAKA CITY UNIVERSITY
• Principal Investigator: MONNA Takeyuki Osaka City University medical school professor, 医学部, 教授 (30046958)
• Co-Investigator(Kenkyū-buntansha): TANAKA Takashi Osaka City Unversity medical school lecturer, 医学部, 講師 (30227144) ; NISHIGUCHI Syuhei Osaka City University medical school lecturer, 医学部, 講師 (10192246)
• Project Period (FY): 1996 – 1997
• Keywords: Glutathione-S-transferase / ornichiredecarboxilaze activity / alcohol

Research Abstract

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.