The effects on cellular functions of bile acid and trypsin in stagnant bile juice in anomalous arrangement of the pancreaticobiliary duct.

To examine the reasons for the high frequency of biliary tract carcinogenesis in individuals with anomalous arrangement of the pancreaticobiliary duct (AAPBD), we investigated the effects on cellular functions of bile acid and trypsin, which are possible risk factors for carcinogenesis found in stagnant bile juice, using a chick embryo fibroblast culture system. Bile acid was found to increase PGE2 synthesis which has been shown to be increased in premalignant lesions, but to suppress the incorporation of [3H]-labelled TdR into DNA. On the other hand, trypsin increased the incorporation of [3H]TdR into DNA, but did not increase PGE2 synthesis. These results suggest that both the bile acid and trypsin present in the stagnant bile juice in AAPBD act to stimulate cell proliferation, but that their mechanisms of action on cell growth differ. Therefore, the combination of these effects of different types of tumor promoters in the stagnant bile juice in AAPBD may account for the high incidence of carcinogenesis.