weH-differentiated ductal adenocarcinoma established from a N-nitroso bis(2-oxopropyl)amine-induced tumor and a poorly differentiated ductal adenocarcinoma established from a spontaneous tumor. An altered mo

This study investigates possible alterations in exons 5 through 8 of the p53 gene and altered p53 protein expression in the Syrian golden hamster model of pancreatic ductal adenocarcinoma. In the Syrian hamster p5.3 sequence, 1469 base pairs are presented for the genomic regions surround ing exons 5 through 8, along with the primer sequences specific for the enzymatic amplification of the individual exons. Single-stranded confor mation polymorphism was analyzed on the products obtained by enzy matic amplification ofhamster genomic DNA extracted from 2 transplant able pancreatic ductal adenocarcinomas, 6 groups of N-methylnitrosourea (MNU)-treated pancreatic duct cells, and 17 MNIJ-induced pancreatic ductal adenocarcinomas. The two transplantable adenocarcinomas were a weH-differentiated ductal adenocarcinoma established from a N-nitroso bis(2-oxopropyl)amine-induced tumor and a poorly differentiated ductal adenocarcinoma established from a spontaneous tumor. An altered mo bility indicated a conformational change in the first part of exon S in the solid form of the well-differentiated ductal adenocarcinoma. Direct se quencing of the amplified product revealed an A—+Ctransversion in codon 135, which corresponds to codon 132 in the human p5.3 gene. A conformational change in exon 7 was observed in 1 of 6 MNU-treated cell samples, and none of the 17 resultant tumors. Direct sequencing con finned a deletion of one C of the three in codon 263, which generates a frameshift mutation. No conformational change was observed in any other products. Positive staining with PAb24O or D07 antibodies against human p53 or with an antibody generated in our laboratory against the hamster p53 fusion protein was observed only in the solid form of well-differenti ated ductal adenocarcinoma and in rare cells scattered in 4 of 28 MNU induced tumors analyzed. This study provides a system to analyze p53 gene alterations in the hamster and is the initial report of a specific p5.3 mutation in a hamster pancreatic ductal adenocarcinoma.