ACTIVATION OF THE KI-RAS PROTOONCOGENE IN SPONTANEOUSLY OCCURRING AND CHEMICALLY-INDUCED LUNG-TUMORS OF THE STRAIN-A MOUSE
ACTIVATION OF THE KI-RAS PROTOONCOGENE IN SPONTANEOUSLY OCCURRING AND CHEMICALLY-INDUCED LUNG-TUMORS OF THE STRAIN-A MOUSE
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DOI：
10.1073/pnas.86.9.3070
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发表时间：
1989-05-01
影响因子：
11.1
通讯作者：
ANDERSON, MW
中科院分区：
文献类型：
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作者：
YOU, M;CANDRIAN, U;ANDERSON, MW
A品系小鼠自发性肺癌发生率高，对化学致癌物诱发肺癌敏感。利用转基因、Southern印迹分析和DNA扩增技术，我们在A系小鼠自发和化学诱导的肺癌组织的DNA中检测到了激活的Ki-ras基因。自发性肺肿瘤中密码子12(60%)和密码子61(30%)均有点突变。而甲基亚硝脲诱发的肺癌Ki-ras基因突变百分率为100%，苯并[a]芘诱发肺癌Ki-ras基因突变的93%位于密码子12，而氨基甲酸乙酯诱发的肺癌Ki-ras基因突变有90%位于密码子61。与自发性肿瘤相比，在化学诱导的肿瘤中观察到的Ki-ras癌基因突变的选择性，表明这些化学物质直接诱导Ki-ras原癌基因的点突变。这些数据表明，A株小鼠肺肿瘤模型是一个非常敏感的系统，可以检测化学物质激活肺组织中Ki-ras原癌基因的能力。
The strain A mouse has a high incidence of spontaneous lung tumors and is susceptible to lung tumor induction by chemical carcinogens. By utilizing transfection assay, Southern blot analysis, and DNA amplification techniques, we have detected an activated Ki-ras gene in the DNAs of both spontaneously occurring and chemically induced lung tumors of strain A mice. The point mutations in the spontaneous lung tumors were in both codon 12 (60%) and codon 61 (30%). In contrast, 100% of the mutations in the Ki-ras gene detected in methylnitrosourea-induced lung tumours and 93% of the mutations in the Ki-ras genes detected in benzo[a]pyrene-induced lung tumors were in codon 12, whereas 90% of the mutations in the Ki-ras genes detected in ethyl carbamate-induced lung tumors were in codon 61. The selectivity of mutations in the Ki-ras oncogene observed in chemically induced tumours, as compared to spontaneous tumors, suggests that these chemicals directly induce point mutations in the Ki-ras protooncogene. These data indicate that the strain A mouse lung tumor model is a very sensitive system to detect the ability of chemicals to activate the Ki-ras protooncogene in lung tissue.