BILE-ACID LOAD ON THE DNA DISTRIBUTION PATTERN OF BILE DUCTULES AND CHOLANGIOCARCINOMA INDUCED BY DIISOPROPANOLNITROSAMINE IN HAMSTERS

This study evaluated the influence of bile acid load on the DNA distri bution pattern of proliferated bile ductules and cholangiocarcinoma in duced by diisopropanolnitrosamine. Ninety hamsters were separated into control, tauro- and deoxycholic acid (DCA) groups. The DNA distributi on pattern of intrahepatic lesions at 15-25 weeks was measured by cyto fluorometry and classified into three types: I (-A, -B), II and III, a ccording to the degree of dispersion on the DNA histogram. Regarding p roliferated bile ductule lesions, all groups showed an increase in cel l populations, indicating the dispersion of nuclear DNA content from t he 4C to 6C ranges over the course of 25 weeks, and two groups with bi le acids, especially the DCA group, revealed significant high incidenc es of lesions with type I-B plus II compared with those in the control group (p < 0.05, 0.01). Changes in carcinoma types were similar to th ose of bile ductule lesions, and the tumors in the DCA group had a sig nificant high frequency of type II plus III (p < 0.05). In addition, h eterogeneity of the DNA distribution pattern was observed within indiv idual lesions of not only carcinoma but also bile ductules. These resu lts suggest that bile acid load, especially DCA, promotes an increase in nuclear DNA content or DNA polyploidization and enhances the distri bution of the DNA pattern of proliferating bile ductules and carcinoma . Furthermore, a bile ductule-carcinoma sequence may be present in the development of cholangiocarcinoma.