[Studies on initiating activity of secondary bile acids for rat hepatocarcinogenesis]

Abstract

The initiating potential of the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), was investigated using the development of preneoplastic lesions in the rat liver as a marker. In a short-term assay in which DCA and LCA were given in the diet for 3 weeks in conjunction with partial hepatectomy midway followed by the selection regimen, DCA dose-dependently induced gamma-glutamyltranspeptidase (gamma-GTP)-positive foci, but the results for LCA were less unequivocal and no dose-dependency was evident. In another experiment, I extended the period of observation and examined whether the gamma-GTP-positive foci thus induced by the secondary bile acids can develop into hepatic tumors after a latent period of 52 weeks with or without the administration of phenobarbital (PB), a promoter of experimental hepatocarcinogenesis. Whereas significantly high numbers of hyperplastic liver nodules developed in the DCA-treated rats irrespective of PB promotion, no such increase was evident in the LCA-treated rats. In contrast, both DCA and LCA treatments enhanced the development of glutathione S-transferase placental form (GST-P)-positive foci with or without subsequent PB promotion. The present data indicate that a short period of administration of DCA and LCA in the initiation stage in conjunction with partial hepatectomy results in enhanced development of preneoplastic liver lesions under selection pressure conditions with or without subsequent PB promotion. This suggests that these secondary bile acids possess possible initiating activity for rat hepatocarcinogenesis.