Study on the mechanism of the carcinogenesis of the biliary tract.

点击翻译按钮获取中文摘要

Anomalous pancreaticobiliary duct union and presence of stones or parasites in ttie biliary tract are well-known high risk groups of biliary tract cancers, liowever, the mechanisms of the carcinogenesis have not been elucidated. Since most of the chemicals are metabolized in the liver, biliary epithelium are firstly and directly exposed to the activated carcinogens if they are ingested. Nevertheless the incidence of the biliary tract cancer is not so high as supposed. One of the reasons may be the rapid excretion of bile through biliary tract to the duodenum in disease free state, which makes the exposure time to the carcinogens too short for the epithelial DNA to be itijured. In the high risk groups bile stasis makes the exposure time lorig enough for DNA injury. In addition bile stasis should increase the cell cycle of the biliary epithelium by induction of the cell degeneration and the regeneration. We supposed that the increase in the cell cycles makes the chance of DNA injury enhanced. In the present study we investigated the modulators of cell cycle and the effect of the increase in the cell cycle on DNA injuries by the use of primary gallbladder epithelial cell culture/ in situ nick translation model. EGF and lithocholic acid increased the BrdU labeled cells and DNA injuries by MNNG were significantly enhanced by the presence of EGF arid/or lithocholic acid. Thus our hypothesis that the increase in the cell cycle as occurred iii the high risk groups enhances the chance of DNA injury which must be the first step of carcinogenests has been verified. The roles of sex hormones, cholesterol and/or other bile acids are now on study.