IDENTIFICATION OF AN ACTIVATED C-KI-RAS ONCOGENE IN RAT-LIVER TUMORS INDUCED BY AFLATOXIN-B1
IDENTIFICATION OF AN ACTIVATED C-KI-RAS ONCOGENE IN RAT-LIVER TUMORS INDUCED BY AFLATOXIN-B1
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DOI：
10.1073/pnas.83.24.9418
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发表时间：
1986-12-01
影响因子：
11.1
通讯作者：
WOGAN, GN
中科院分区：
文献类型：
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作者：
MCMAHON, G;HANSON, L;WOGAN, GN
在2个月的时间里，断奶的雄性Fischer大鼠被给予40次黄曲霉毒素B1(每只动物每天25微克)的腹膜注射。这种慢性给药方案导致所有接受治疗的动物依次形成增生灶、癌前结节和肝细胞癌。在NIH3T3-小鼠成纤维细胞中，通过形成非锚定非锚定小灶来检测转化DNA序列的存在。从8种动物的单个肿瘤中分离出的基因组DNA被转染后，每微克DNA的特异转化活性从0.05到0.2个焦点不等。用c-Ha-ras、c-ki-ras和N-ras癌基因同源DNA探针进行Southern杂交分析。在接受测试的八只动物中，有两只的肿瘤转化体中检测到了高度扩增的鼠源性c-ki-ras癌基因。没有证据表明在任何转化子中都存在c-Ha-ras或N-ras序列。对原发性肝肿瘤DNA的分析显示，与对照肝DNA样本相比，没有Ki-ras DNA扩增。在含有活化大鼠c-ki-ras基因的3T3转化子中，检测到c-ki-ras p21蛋白表达水平升高。大鼠来源的c-ki-ras序列的存在可以被认为是c-ki-ras基因在原发性肝肿瘤中被激活的证据。
Weanling male Fischer rats were administered 40 intraperitoneal injections of aflatoxin B1 (25 .mu.g per animal per day) over a 2-month period. This chronic dosing regimen resulted in the sequential formation of hyperplastic foci, preneoplastic nodules, and hepatocellular carcinomas in all of the animals treated. The presence of transforming DNA sequences was detected by formation of anchorage-independent foci after transfection of tumor-derived DNA in NIH 3T3- mouse fibroblasts. Transfection of genomic DNA isolated from individual tumors from eight animals resulted in specific transforming activities ranging from 0.05 to 0.2 foci per .mu.g of DNA. Primary transfectant DNAs were analyzed by Southern blot hybridization with DNA probes homologous to c-Ha-ras, c-Ki-ras, and N-ras oncogenes. A highly amplified c-Ki-ras oncogene of rat origin was detected in transformants derived from tumors in two of the eight animals tested. There was no evidence to suggest the presence of c-Ha-ras or N-ras sequences in any of the transformants. Analysis of primary liver tumor DNA showed no Ki-ras DNA amplification when compared to control liver DNA samples. Increased levels of c-KI-ras p21 proteins were detected in 3T3 transformants containing activated rat c-Ki-ras genes. The presence of c-Ki-ras sequences of rat origin capable of inducing transformed foci can be taken as evidence that the c-Ki-ras gene has been activated in the primary liver tumors.