INHIBITION BY GOMISIN-A, A LIGNAN COMPOUND, OF HEPATOCARCINOGENESIS BY 3'-METHYL-4-DIMETHYLAMINOAZOBENZENE IN RATS

The effects of gomisin A, a lignan compound of Schizandra fruits, on h epatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene (3' -MeDAB) in rats were investigated. Gomisin A inhibited both increases of the number and size of glutathione S-transferase placental form (GS T-P)-positive foci, a marker enzyme of preneoplasm, and the population of diploid nuclei, as a proliferative state of hepatocytes, in the li ver from rats simultaneously treated with 3'-MeDAB. Gomisin A increase d GST activity in the liver, by raising the level of GST 1 and 2 isozy mes. 3'-MeDAB increased GST activity and GST-P expression. This high l evel of GST-P induced by 3'-MeDAB was suppressed by additional treatme nt with gomisin A. In an experiment on simultaneous treatment, gomisin A increased the biliary excretion of 3'-MeDAB-related aminoazo dyes a nd decreased the content in the liver of rats fed with 0.06%-3'-MeDAB containing diet. In an experiment on pretreatment with 3-MeDAB, even t hough no aminoazo dye was detectable in the liver or bile 2-weeks afte r cessation of 3'-MeDAB-feeding, gomisin A showed a tendency to reduce the preneoplastic changes of increases in GST-P positive foci and dip loid nuclei in the liver. These results suggest that gomisin A inhibit s the hepatocarcinogenesis induced by 3'-MeDAB by enhancing the excret ion of the carcinogen from the liver and by reversing the normal cytok inesis.