Background and objectives:
In our laboratory, we have developed a new model of carcinoma of the bile duct in syrian golden hamsters, using n-nitrosobis(2-oxopropyl)amine (bop). morphologic and biologic characteristics of the carcinoma induced in this model are similar to those seen in humans. in order to examine the gene-related carcinogenesis of intrahepatic bile duct carcinoma, we investigated mutations in the k-ras gene in various early hyperplastic and neoplastic lesions of these hamsters, according to the original sites of the lesions.
Methods:
Inbred female hamsters were given a subcutaneous injection of n-nitrosobis(2-oxopropyl)amine (bop) following dissection of the extrahepatic bile duct on the distal end of the common duct and preparation of a cholecystoduodenostomy (cddb) or simple laparotomy (sl). neoplastic lesions arising from the intrahepatic bile duct were histologically examined, and k-ras mutations were investigated.
Results:
Mutations of k-ras codon 12 were evident in 12% of tubular hyperplasias, 19% of tubular adenocarcinomas, 15% of papillary hyperplasias and 36% of papillary adenocarcinomas. in papillary adenocarcinoma arising from a large bile duct, k-ras mutations occurred more frequently than in tubular adenocarcinoma arising from ductule or ductular proliferation. k-ras mutations were present even in a hyperplasia; the positive rates of the mutations increased in the presence of a carcinoma. genetic changes in carcinoma of the intrahepatic bile duct varied based on sites of the duct and the histological type.
Conclusions:
A part of the hyperplastic lesions of the intrahepatic bile duct presented k-ras gene mutation. this suggests that k-ras gene mutation is an early event in the carcinogenic process. in carcinoma of the intrahepatic bile duct, the lesion arising from a large bile duct of the hepatic hilum tended to exhibit a higher frequency of k-ras gene mutation than did a tubular lesion arising from ductule or ductal proliferation. this hamster model is useful to examine the carcinogenesis of human intrahepatic bile duct carcinoma.