Mutations of K-ras but not p53 genes in biliary duct and pancreatic duct carcinomas induced in hamsters by cholecystoduodenostomy with dissection of the common duct followed by N-nitrosobis(2-oxopropyl)amine.

An experimental model for the induction of extrahepatic biliary duct carcinomas in hamsters given cholecystoduodenostomy with dissection of the extrahepatic duct at the distal end of the common duct (CDDB) followed by N-nitrosobis(2-oxopropyl)amine (BOP) has been reported [Tajima et al. (1994) Jpn. J. Cancer Res., 85, 780-788]. The CDDB procedure greatly accelerates cell turnover in the biliary epithelium. In the present experiment, mutations of K-ras and p53 genes in the induced lesions were investigated by the reverse transcriptase-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) method followed by direct sequencing. Mutations of K-ras, involving a G to A transition in second position of codon 12 of K-ras exon 1, were detected in six out of eight (75%) extrahepatic bile duct carcinomas and six out of eleven (54.5%) pancreatic duct carcinomas. However, no mutations of p53 were observed in either tumor type. The results indicate an association between anomalous pancreaticobiliary junction and development of biliary carcinomas that may be pertinent to the human situation, and indicate that conditions of the model predispose to mutations occurring in K-ras but not p53.