Pancreatic ductal adenocarcinomas induced in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine contain a c-Ki-ras oncogene with a point-mutated codon 12

Abstract

We have used the polymerase chain reaction and dideoxynucleotide sequencing to amplify and sequence exons 1 and 2 of the c-Ki-ras proto-oncogene from the normal Syrian golden hamster. Similar methods were employed to screen for the presence of point mutations in the c-Ki-ras oncogene in primary hamster pancreatic ductal adenocarcinomas (PDC) induced by N-nitrosobis(2-oxopropyl)amine (BOP). A GGT to GAT point mutation was detected in codon 12 of the c-Ki-ras gene in 10 primary hamster PDCs. This same point mutation was present in two nonclonal cell lines, PC-1 and PC-1-0, established from tumors that were produced in hamsters by subcutaneously implanting a preparation of minced BOP-induced PDC. Two clonal cell lines, Cl-3 and Cl-7, were cloned from the PC-1 cell line, and these cell lines also carried the GAT point mutation at codon 12. This point mutation was the same as that detected in greater than 75% of adenocarcinomas from the human exocrine pancreas. Thus, our findings provide further validation for the use of the BOP-induced hamster PDC model as a relevant experimental model for human pancreas cancer: not only did the hamster pancreatic ductal adenocarcinomas closely resemble their human counterpart in histopathological morphology and sequential development, but they also contained the same point mutation in codon 12 of the c-Ki-ras oncogene, as has been reported for human pancreatic adenocarcinomas.