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

接受 TFE 的 B6C3F1 小鼠肝肿瘤中 RAS 癌基因突变

• 批准号: 2452840
• 负责人: H L HONG
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2452840
• 关键词: chemical carcinogen; chemical carcinogenesis; environmental toxicology; fluorocarbon polymers; gene mutation; hepatocellular carcinoma; laboratory mouse; liver neoplasms; longitudinal animal study; nucleic acid sequence; oncogenes; restriction fragment length polymorphism; single strand conformation polymorphism

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.

在B6 C3 F1小鼠中有明确的肝癌活性证据 暴露于三氟氯乙烯（TFE）2年后。本 本研究旨在描述肝脏中H-和K-ras癌基因的特征 在接触0、312、625或1250 ppm TFE的小鼠中诱发肿瘤。Ras 通过限制性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 从冷冻或石蜡包埋的肝脏中分离的PCR扩增DNA 肿瘤。H-ras基因第61位密码子突变率为15%（9/59）， 与高频率相比， (59本研究的%和历史数据的56%） 肿瘤。突变频率和突变谱无差异 在接触组之间或在良性和恶性肝细胞之间 肿瘤。K-ras基因第12、13和61位密码子突变在20例正常人中均未检出。 肝细胞肿瘤 这些数据表明，TFE诱导的 肝细胞肿瘤通过大多数独立于ras的途径发展 激活，并不同于自发肝 肿瘤。