Abstract

It has been generally accepted that sequential histological changes develop during the course of hepatocarcinogenesis as the precancerous lesions. However, the exact pathogenic mechanism and the relationship between these precancerous lesions and carcinoma remain contro- versiaL In 3'-methyl-4-dimethylaminoazobenzene(3'-MeDAB) induced hepatocarcinogenesis, the intermediate metabolites produced by cytochrome P, oxidase system of hepatocytes are thought to be the ultimate carcinogen, and conceivably such drugs as ethanol which is also oxidized by the same hepatic oxidase system may affect the 3-MeDAB induced hepatocarcinogenesis. The present study aimed to elucidate that the cytokinetic nature of the hepatic lesions developed by 3'-MeDAB administration and the effect of ethanol on the course of hepatocarcinogenesis. Sprague-Dawley male rats about 180 g were used for the experiment, and divided into 8 groups according to the duration and doses of 3-MeDAB and ethanol administered: I. normal control, IL 3-MeDAB only for 6 weeks, III. 3'-MeDAB only for 9 weeks, IV. 3'-MeDAB with a small dose(4 g/kg) of ethanol, V. 3'-MeDAB with a large dose(ll g/kg) of ehtanol, VL ethanol pretreatment for 3 weeks followed by 3'-MeDAB plus ethanol for 9 weeks, VII. Ethanol only for 9 weeks in a small dose, VIII. Ethanol only for 9 weeks in a large dose. Animals were sacrificed at 3, 6, 9, 12 and 15 weeks. The liver weight, the gross and microscopical changes of the liver were compered between the experimental groups. Cell kinetics of the various hepatic lesions developed in the hepatocarcinogenesis was examined by applying the immunohistochemical method for bromodeoxyuridine(BrdU). The results are as follows: 1) Liver weights tended to increase gradually in the experimental groups treated with 3'- MeDAB with or without ethanol, whereas it decreased in the animals given ethanoi alone. 2) The number and size of hepatic granules, nodules and masses continued to increaae in the