Tsutsumi M, Kondoh S, Noguchi O, Horiguchi K, Kobayashi E, Okita S, Ohashi K, Honoki K, Tsujiuchi T, Konishi Y
Department of Oncological Pathology, Nara Medical University.
Jpn J Cancer Res. 1993 Nov;84(11):1101-5. doi: 10.1111/j.1349-7006.1993.tb02807.x.
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.
在实验诱导的胰腺导管癌前病变中检测K-ras基因突变。叙利亚仓鼠接受70mg/kg的N-亚硝基双（2-氧代丙基）胺（BOP），随后反复暴露于由胆碱缺乏饮食联合DL-乙硫氨酸和L-甲硫氨酸组成的强化压力方案，并给予20mg/kg BOP。经过两个强化压力周期后，出现胰腺导管细胞增生，三个周期后，发生胰腺导管细胞非典型增生和导管内癌。通过聚合酶链反应产物的单链构象多态性分析和核苷酸测序检测K-ras突变。结果显示，在9例胰腺导管上皮单纯增生中有1例发生K-ras突变，9例非典型增生中有5例发生K-ras突变，8例导管内癌中有4例发生K-ras突变。因此，这些发现表明K-ras在仓鼠胰腺导管细胞非常早期的恶性转化过程中被激活。
