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.
Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
Mami
M
Furukawa
Ayako
A
Yamasaki
Junichi
J
Yoshida
Megumu
M
Tsujino
Naoko
N
Wakabayashi
Kanya
K
Honoki
Toshifumi
T
Tsujiuchi
D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D006224:Cricetinae; D005260:Female; D008647:Mesocricetus; D009153:Mutagens; D009602:Nitrosamines; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009153:Mutagens; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine; D017346:Protein Serine-Threonine Kinases