RAS ONCOGENE MUTATIONS IN LIVER NEOPLASMS OF B6C3F1 MICE ESPOSED TO TFE

有明确的证据表明B6C3F1小鼠具有肝癌活性 在接触四氟乙烯(TFE)2年后。现在 这项研究旨在研究肝脏中H-和K-ras癌基因的特征 暴露于0、312、625或1250ppm TFE的小鼠诱发肿瘤。RAS 通过限制性内切酶片段长度多态性鉴定突变， 单链构象多态性分析和直接测序 从冰冻或石蜡包埋的肝脏中提取的 肿瘤。H-ras密码子61突变频率较低(15%，9/59 在肝细胞肿瘤中检测到的与高频率相比 (本研究的59%和历史数据的56%) 肿瘤。突变频率和突变谱无明显差异 在暴露组之间或在良性和恶性肝细胞之间 肿瘤。未检测到K-ras基因第12、13和61位密码子突变 肝细胞肿瘤。这些数据表明，TFE诱导的 肝细胞肿瘤的发展途径大多不依赖ras。 活化，与自发肝的活化不同 肿瘤。

There was clear evidence of hepatocarcinogenic activity in B6C3F1 mice following 2 years of tetrafluoroethylene (TFE) exposure. The present study was designed to characterize the H- and K-ras oncogenes in liver neoplasms induced in mice exposed to 0, 312, 625 or 1250 ppm TFE. Ras mutations were identified by restriction fragment length polymorphism, single strand conformation polymorphism analysis and direct sequencing of PCR amplified DNA isolated from frozen or paraffin-embedded liver neoplasms. A low frequency (15% 9/59) of H-ras codon 61 mutation was detected in hepatocellular neoplasms when compared to the high frequency (59% of this study and 56% of historical data) in spontaneous liver neoplasms. There was no difference in the mutation frequency and spectrum among exposure groups or between benign and malignant hepatocellular neoplasms. K-ras mutations at codons 12, 13 and 61 were not detected in hepatocellular neoplasms. These data suggest that TFE-induced hepatocellular neoplasms develop by pathways mostly independent of ras activation, and that are different from those of spontaneous liver neoplasms.