Although hepatocarcinogensis has been reported to be promoted by exogenous administration of
bile acids, the relation of endogenous
bile acids to hepatocarcinogenesis is not completely understood. This study investigates the relationship between serum concentration of
bile acids, the appearance of preneoplastic change,
glutathione S-transferase placental form (GST-P)-positive foci in the liver of male Donryu rats which had been fed 0.06% 3'-methyl-4-dimethylamino-azobenzene (3'-MeDAB), and the effects of
gomisin A, previously reported to inhibit the
tumor promotion process. During the feeding of 3'-MeDAB for 5 weeks, the concentrations of serum
bile acids were found to have increased significantly to several times the levels found at the start of the experiment. The increase of serum
bile acids, especially
deoxycholic acid (DCA), and the appearance of preneoplastic lesions, the number and area of GST-P-positive foci in the liver, were significantly inhibited by simultaneous
oral administration of
gomisin A (30 mg/kg). When DCA (100 mg/kg) was orally administered after an initiation by 3'-MeDAB, serum
bile acids and preneoplastic changes were significantly increased, these increases were inhibited by combined feeding of 0.03%
gomisin A in the diet. There were good correlations between the serum concentration of DCA and the number of GST-P-positive foci in the liver in both experimental protocols. These results confirm that DCA is an endogenous risk factor for hepatocarcinogenesis and suggest that anti-promoter effect of
gomisin A is based on improving metabolism of
bile acids, including DCA.