Activation of c-K-ras is frequent in pancreatic carcinomas of Syrian hamsters, but is absent in pancreatic tumors of rats.
We have investigated the presence of mutations in ras genes at codons 12, 13 and 61 in chemically induced pancreatic tumors of rats and Syrian hamsters. Mutations were detected by means of allele-specific oligonucleotide hybridization to ras sequences amplified in vitro by the polymerase chain reaction. No mutations were observed in the c-K-ras gene or the c-H-ras gene of nine azaserine-induced adenomas and 15 carcinomas of the rat pancreas. This indicates that activated ras genes are not commonly involved in rat pancreatic cancer evolving from acinar cells. However, in 19 out of 20 ductular adenocarcinomas of hamster pancreas (95%), either codon 12 or 13 of the c-K-ras gene was mutated. This indicates that the activation of c-K-ras is a frequent event in the multistep process of pancreatic carcinogenesis induced by the alkylating carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). The mutations of both codons were G----A transitions of the second base which is consistent with the type of mutation to be expected from DNA alkylation. Activation of the c-K-ras gene, therefore, may not only be a frequent but also an early event in hamster pancreas carcinogenesis. The frequent activation of the c-K-ras gene in both human and hamster pancreatic cancer emphasizes the relevance of BOP-induced pancreatic adenocarcinomas in Syrian hamsters as an experimental model system for studying human pancreatic cancer.
van Kranen
H J
HJ
Laboratory of Carcinogenesis and Mutagenesis, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Vermeulen
E
E
Schoren
L
L
Bax
J
J
Woutersen
R A
RA
van Iersel
P
P
van Kreijl
C F
CF
Scherer
E
E
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003062:Codon; D006224:Cricetinae; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000235:genetics*; D016133:Polymerase Chain Reaction; D051381:Rats
D003062:Codon