ONCOGENE ALTERATION IN MICE INDUCED BY ISOPRENE

异戊二烯引起的小鼠癌基因改变

• 批准号: 2574287
• 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/2574287
• 关键词: chemical carcinogen; chemical carcinogenesis; chemical related neoplasm /cancer; environmental toxicology; eye neoplasms; gene induction /repression; gene mutation; isoprenoid; laboratory mouse; male; neoplasm /cancer genetics; oncogenes; protooncogene

A higher frequency of ras mutations, in particular K-ras mutations, was detected in isoprene-induced neoplasms than in 1,3-butadiene-induced or control HG neoplasms. All of the isoprene-induced HG neoplasms exhibited activated K-ras (60%) or H-ras (40%) mutations. In contrast, ras mutations were detected in 69% of HG neoplasms from 1,3-butadiene exposed mice (14% K-ras and 55% H-ras) and in 56% of HG neoplasms obtained from control B6C3F1 mice (8% K-ras and 48% H-ras). The predominant mutations in isoprene-induced HG neoplasms, but not in previously or newly analyzed 1,3-butadiene-induced HG neoplasms, consisted of A-T transversions (CCC-CTA) at K-ras codon 61 (15/30) and C-A transversions (CAA-AAA) at H-ras codon 61 (8/30). Two thirds of the K-ras CTA mutations were detected in HG neoplasms from the 2200 ppm exposure group while one third was present in the 7000 ppm group. Compared to the surrounding non-tumor HG tissue, HG neoplasms with K-ras or H-ras mutations had an elevated proliferating cell nuclear antigen (PCNA) index. The high frequency and specificity of the ras mutation profile suggest that ras protooncogene activation contributes to isoprene-induced HG tumorigenesis.

ras基因突变，特别是K-ras基因突变的频率较高， 在异戊二烯诱导的肿瘤中检测到的比在1，3-丁二烯诱导的或 控制HG肿瘤。所有异戊二烯诱导的HG肿瘤均表现出 激活的K-ras（60%）或H-ras（40%）突变。相比之下，ras 在1，3-丁二烯暴露的HG肿瘤中检测到69%的突变 小鼠（14% K-ras和55% H-ras）和56%的HG肿瘤， 对照B6 C3 F1小鼠（8% K-ras和48% H-ras）。主要突变 在异戊二烯诱导的HG肿瘤中，但在先前或新分析的 1，3-丁二烯诱导的HG肿瘤，由A-T颠换组成 K-ras密码子61（15/30）处的CCC-CTA和K-ras密码子61处的C-A颠换（CAA-AAA）。 H-ras第61位密码子（8/30）。三分之二的K-ras CTA突变是 在2200 ppm暴露组的HG肿瘤中检测到， 在7000 ppm组中存在。与周围的非肿瘤相比 在HG组织中，具有K-ras或H-ras突变的HG肿瘤具有升高的 增殖细胞核抗原（PCNA）指数。这两次频密和 ras突变谱的特异性提示ras原癌基因 激活有助于异戊二烯诱导的HG肿瘤发生。