Y. Kinami et al., BILE-ACID LOAD ON THE DNA DISTRIBUTION PATTERN OF BILE DUCTULES AND CHOLANGIOCARCINOMA INDUCED BY DIISOPROPANOLNITROSAMINE IN HAMSTERS, Oncology, 55(1), 1998, pp. 77-86
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.