Tsujiuchi Toshifumi, Furukawa Mami, Obo Yumi, Yamasaki Ayako, Hotta Mayuko, Kusunoki Chie, Suyama Naoko, Mori Toshio, Honoki Kanya, Fukushima Nobuyuki
J Toxicol Pathol. 2009 Mar;22(1):89-92. doi: 10.1293/tox.22.89. Epub 2009 Apr 6.
To evaluate the involvement of lysophosphatidic acid receptor-1 (LPA1) gene alteration in pancreatic carcinogenesis, we investigated mutations in the LPA1 gene in hamster pancreatic duct adenocarcinomas (PDAs) and established cell lines. Female Syrian golden hamsters received 30 mg/kg of N-nitrosobis(2-oxopropyl)amine (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 a further administration of 20 mg/kg BOP. A total of 10 PDAs obtained 10 weeks after beginning the experiment and three cell lines established from subcutaneously transplantable PDAs in syngeneic hamsters were examined for mutations using reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis. A mutation was detected in only one PDA (1/10, 10%) in the form of a GGA to GTA (Gly to Val) transversion at codon 355, and no mutations were detected in the three cell lines. These results suggest that the LPA1 gene mutation may play roles in a limited fraction of BOP-induced pancreatic duct carcinogenesis in hamsters.
为评估溶血磷脂酸受体-1（LPA1）基因改变在胰腺癌发生中的作用，我们研究了仓鼠胰腺导管腺癌（PDA）及建立的细胞系中LPA1基因的突变情况。雌性叙利亚金仓鼠接受30 mg/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、然后L-甲硫氨酸组成的强化压力方案，并进一步给予20 mg/kg BOP。实验开始10周后获得的总共10个PDA以及从同基因仓鼠皮下可移植PDA建立的3个细胞系，使用逆转录-聚合酶链反应-单链构象多态性（RT-PCR-SSCP）分析检测突变。仅在一个PDA（1/10，10%）中检测到一个突变，为密码子355处的GGA到GTA（甘氨酸到缬氨酸）颠换，在3个细胞系中未检测到突变。这些结果表明，LPA1基因突变可能在仓鼠中BOP诱导的胰腺导管癌发生的有限部分中起作用。
