K-ras gene mutation in early ductal lesions induced in a rapid production model for pancreatic carcinomas in Syrian hamsters.
The presence of K-ras gene mutation was examined in experimentally induced preneoplastic pancreatic ductal lesions. Syrian hamsters received 70 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of choline-deficient diet combined with DL-ethionine and L-methionine and administration of 20 mg/kg BOP. After two augmentation pressure cycles, pancreatic ductal cell hyperplasias appeared and after three cycles, atypical hyperplasias of pancreatic ductal cells and intraductal carcinomas developed. K-ras mutations were detected by single-strand conformation polymorphism analysis of polymerase chain reaction products and nucleotide sequencing. The results showed that K-ras mutation had occurred in one of 9 simple hyperplasias of pancreatic ductal epithelium, in 5 of 9 atypical hyperplasias, and in 4 of 8 intraductal carcinomas. The findings thus suggested that K-ras is activated in association with very early stage malignant transformation of pancreatic ductal cells in hamsters.
Tsutsumi
M
M
Department of Oncological Pathology, Nara Medical University.
Kondoh
S
S
Noguchi
O
O
Horiguchi
K
K
Kobayashi
E
E
Okita
S
S
Ohashi
K
K
Honoki
K
K
Tsujiuchi
T
T
Konishi
Y
Y
D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics*; D003062:Codon; D006224:Cricetinae; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D011905:Genes, ras; D006965:Hyperplasia; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009153:Mutagens; D009154:Mutation; D009602:Nitrosamines; D010183:Pancreatic Ducts / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics*
D003062:Codon; D017931:DNA Primers; D009153:Mutagens; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine