Abstract

To elucidate the effect of copper on the 3'-methyl-4-dimethylaminoazobenzene(3'-MeDAB) induced hepatic carcinogenesis, Sprague-Dawley rats were divided into 4 groups according to 3'-MeDAB and copper administration: I. noraml control, II. copper only, III. 3'-MeDAB only, IV. 3'-MeDAB plus copper. The animals of groups III and IV were fed experimental diet containing 0.06% 3'-MeDAB. Copper was administrated intraperitoneally in a dose of 0.5 mg, twice a weak. Animals were sacrificed at different intervals. Liver weight, hepatic copper content and gross and microscopical changes of the liver were examined and the cell kinetics of various lesions in the hepatic carcinogenesis was studied by applying the immunohistochemical method for bromodeoxyuridine(BrdU). The hepatic copper content was significantly increased in animals given copper but returned to the normal value after cessation of adminstration. 3'-MeDAB administration caused oval cell proliferation and produced hyperplastic nodules, cholangiofibrosis and carcinoma of the liver. Simultaneous administration of copper did not alter the incidence of 3'-MeDAB induced lesions, except for carcinoma. The liver weight and the size of hepatic nodules and masses were smaller in group IV than in group III. The liver weight as well as the nodularity and the mass formation continued to increase affect cessation of 3'-MeDAB administration. Copper did not affect the BrdU labelling indices of the hepatic lesions induced by 3'-MeDAB. The oval cell proliferation and the BrdU labelling indices of the oval cell and the hyperplastic nodule were decreased, but the incidence of cholangiofibrosis and its BrdU labelling index were still elevated after cessation of 3'MeDAB administration. These findings indicate that copper could delay the developement of 3'-MeDAB induced hepatic lesions, but not suppress, since copper does not stay long enough to accumulate in the rat liver, and that copper could not affect the proliferation of 3'-MeDAB induced hepatic lesions once developed.

• Keywords: Hepatic carcinogenesis;3'-Methyl-4-dimethylaminoazobenzene;Copper;Carcinogenesis