Tsujiuchi Toshifumi, Sasaki Yasutaka, Kubozoe Tadahiko, Konishi Yoichi, Tsutsumi Masahiro
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Nara, Japan.
Mol Carcinog. 2003 Feb;36(2):60-6. doi: 10.1002/mc.10099.
Alteration of the Fhit gene was investigated in pancreatic duct adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine (BOP) in Syrian golden hamsters. The animals received 70 mg/kg BOP, followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine and then L-methionine and administration of 20 mg/kg BOP. A total of 15 pancreatic duct adenocarcinomas were obtained 10 wk after the beginning of the experiment, and total RNAs were extracted from each for assessment of aberrant transcription of the Fhit gene by reverse transcription-polymerase chain reaction analysis. Aberrant transcripts lacking nucleotides in the regions of nt -75 to 348, nt -15 to 348, or nt -75 to 178 were detected in 11 adenocarcinomas (73.3%). Southern blot analysis of eight tumors did not show any evidence of gross rearrangement or deletion. These results indicated that changes in the Fhit gene occurred frequently and thus may have played a role in the development of pancreatic duct adenocarcinomas induced by BOP in hamsters.
在叙利亚金仓鼠中，研究了由N-亚硝基双（2-氧代丙基）胺（BOP）诱导的胰腺导管腺癌中Fhit基因的改变。动物接受70mg/kg的BOP，随后反复暴露于由胆碱缺乏饮食联合DL-乙硫氨酸，然后是L-甲硫氨酸以及给予20mg/kg BOP组成的增强压力方案。实验开始10周后共获得15个胰腺导管腺癌，并从每个肿瘤中提取总RNA，通过逆转录-聚合酶链反应分析评估Fhit基因的异常转录。在11个腺癌（73.3%）中检测到在nt -75至348、nt -15至348或nt -75至178区域缺乏核苷酸的异常转录本。对8个肿瘤的Southern印迹分析未显示任何明显重排或缺失的证据。这些结果表明，Fhit基因的改变频繁发生，因此可能在仓鼠中由BOP诱导的胰腺导管腺癌的发生中起作用。
