ONCOGENE ALTERATION IN MICE INDUCED BY ISOPRENE

Ras突变，特别是K-ras突变的频率更高 在异戊二烯诱导的肿瘤中检测到的比1，3-丁二烯诱导的或 控制HG肿瘤。所有异戊二烯诱导的HG肿瘤均表现为 激活的K-ras(60%)或H-ras(40%)突变。相比之下，RAS 在接触1，3-丁二烯的HG肿瘤中，69%检测到突变 小鼠(14%的K-ras和55%的H-ras)和56%的HG肿瘤 对照组B6C3F1小鼠(8%K-ras和48%H-ras)。最主要的突变 在异戊二烯诱导的HG肿瘤中，但在以前或新分析的中没有 1，3-丁二烯诱导的HG肿瘤，包括A-T转换 (CCC-CTA)位于K-ras密码子61(15/30)，C-A颠换(CAA-AAA)位于 H-ras密码子61(8/30)。三分之二的K-ras CTA突变是 在2200ppm暴露组的HG肿瘤中检测到三分之一 出现在7000ppm的组中。与周围非肿瘤组织相比 具有K-ras或H-ras突变的HG组织、HG肿瘤的 增殖细胞核抗原(PC NA)指数。高频率和高频率 Ras基因突变谱的特异性提示ras原癌基因 激活参与了异戊二烯诱导的HG肿瘤的发生。

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.