Promotive effect of primary and secondary bile acids on the induction of gamma-glutamyl transpeptidase-positive liver cell foci as a possible endogenous factor for hepatocarcinogenesis in rats.

Abstract

The promoting effects of 5 bile acids on liver carcinogenesis were investigated in male Fischer rats initially treated with diethylnitrosamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given bile acids for 8 weeks. At 3 weeks following DEN administration, all rats were subjected to partial hepatectomy. Among the bile acids tested, cholic acid (CA) and deoxycholic acid (DCA) exerted promoting activity as evidenced by significantly increased values of gamma-glutamyl transpeptidase-positive (gamma-GT+) foci as compared with the corresponding controls given DEN alone. In contrast, the other 3 bile acids tested, chenodeoxycholic acid (CDCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA), did not significantly increase the level of gamma-GT+ foci over that induced by DEN alone. It is noteworthy that only bile acids of the same metabolic pathway, CA as a primary bile acid and DCA as a secondary bile acid, showed promoting effects whereas CDCA and its metabolic derivatives, LCA and UDCA, were inactive. The results indicate that CA and DCA might act as endogenous promoters of hepatocarcinogenesis in pathological conditions with increased levels of serum bile acids.