Mutations of LKB1 Gene in Pancreatic Ductal Adenocarcinomas Induced by N-Nitrosobis(2-oxopropyl)amine in Hamsters

To evaluate an involvement of LKB1 gene alteration during pancreatic carcinogenesis, mutations in the LKB1 gene in hamster pancreatic duct adenocarcinomas (PDAs) induced by N-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Female Syrian golden hamsters received 30 mg/kg of BOP followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine then L-methionine and a further administration of 20 mg/kg BOP. A total of 10 PDAs obtained 10 weeks after beginning the experiment were examined for mutations using reverse transcription (RT)-polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Mutations were detected in 3 out of the 10 PDAs (30.0%). Sequence analysis revealed the identity of these mutations to be a CCC to CCT (Pro to Pro) transition at codon 221, a CCG to CAG (Pro to Gln) transversion at codon 324 and a GAC to GGC (Asp to Gly) transition at codon 343. The LKB1 gene may be involved in the development of PDAs induced by BOP in hamsters.