Detection and identification of activated oncogenes in spontaneously occurring benign and malignant hepatocellular tumors of the B6C3F1 mouse.
Detection and identification of activated oncogenes in spontaneously occurring benign and malignant hepatocellular tumors of the B6C3F1 mouse.
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B6C3F1 小鼠自发性良性和恶性肝细胞肿瘤中活化癌基因的检测和鉴定。
DOI：
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发表时间：
1986
影响因子：
11.1
通讯作者：
S. Aaronson
中科院分区：
文献类型：
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作者：
S. Reynolds;S. Stowers;R. Maronpot;M. Anderson;S. Aaronson
在正常实验室条件下饲养的啮齿动物中观察到了特定物种和菌株的自发性肿瘤。阐明与这些自发性肿瘤发展相关的分子机制可能有助于更好地了解与接触化学致癌物相关的肿瘤发展。鉴于已知的化学致癌物在啮齿动物肿瘤中表现出较高的癌基因激活频率，我们用DNA转基因技术研究了B6C3F1小鼠和Fischer 344/N大鼠自发肿瘤中的癌基因激活。在这项研究中观察到自发性大鼠肿瘤和自发性小鼠肝肿瘤中激活的癌基因的存在显著不同。所有大鼠肿瘤均未产生激活的癌基因(0/29)，而30%(3/10)的小鼠肝细胞腺瘤和77%(10/13)的肝细胞癌DNA转染组阳性。这些转化基因在所有腺瘤转染者中均为激活的Ha-ras基因，在10例癌转染者中有8例被鉴定为激活的Ha-ras基因。剩下的两个肝细胞癌含有转化基因，似乎不是已知的ras基因家族的成员。B6C3F1小鼠肝脏系统不仅可用于评估一种化学物质激活细胞原癌基因的潜力，而且可用于检测各种易受突变激活的原癌基因。
Species- and strain-specific spontaneously occurring tumors have been observed in rodents maintained under normal laboratory conditions. Elucidation of the molecular mechanisms associated with the development of these spontaneous tumors may provide a better understanding of tumor development associated with exposure to chemical carcinogens. In view of the high frequencies of oncogene activation shown in rodent tumors induced by known chemical carcinogens, we have investigated oncogene activation in spontaneous tumors of the B6C3F1 mouse and Fischer 344/N rat by DNA transfection techniques. A marked difference in the presence of activated oncogenes in spontaneous rat tumors versus spontaneous mouse liver tumors was observed in this study. All rat tumors tested failed to yield activated oncogenes (0/29), whereas 30% (3/10) of mouse hepatocellular adenomas and 77% (10/13) of hepatocellular carcinomas scored positive by DNA transfection. These transforming genes were identified as an activated Ha-ras gene in all the adenoma transfectants and in 8 of the 10 carcinoma transfectants. The two remaining hepatocellular carcinomas contained transforming genes that appear not to be members of the known ras gene family. The B6C3F1 mouse liver system might provide a very sensitive assay not only for assessing the potential of a chemical to activate a cellular proto-oncogene, but also for detecting various classes of proto-oncogenes that are susceptible to mutational activation.