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 c arcinomas in hamsters given cholecystoduodenostomy with dissection of the extrahepatic duct at the distal end of the common duct (CDDB) foll owed by N-nitrosobis(2-oxopropyl)amine (BOP) has been reported [Tajima et al. (1994) Jpn, J. Cancer Res., 85, 780-788]. The CDDB procedure g reatly accelerates cell turnover in the biliary epithelium. In the pre sent experiment, mutations of K-ras and p53 genes in the induced lesio ns were investigated by the reverse transcriptase-polymerase chain rea ction-single strand conformation polymorphism (RT-PCR-SSCP) method fol lowed by direct sequencing. Mutations of K-ras, involving a G to A tra nsition in second position of codon 12 of K-ras exon I, were detected in six out of eight (75%) extrahepatic bile duct carcinomas and six ou t of eleven (54.5%) pancreatic duct carcinomas. However, no mutations of p53 were observed in either tumor type. The results indicate an ass ociation between anomalous pancreaticobiliary junction and development of biliary carcinomas that may be pertinent to the human situation, a nd indicate that conditions of the model predispose to mutations occur ring in K-ras but not p53. (C) 1997 Elsevier Science Ireland Ltd.