Barbacid M
Developmental Oncology Section, Frederick Cancer Research Facility, Maryland 21701.
Princess Takamatsu Symp. 1986;17:43-53.
More than fifteen different oncogenes have already been identified in human tumors to date. Some of these oncogenes, in particular those of the ras gene family, have been found to be reproducibly activated in a variety of carcinogen-induced animal tumor systems. In rats, almost 90% of the mammary carcinomas induced by a single dose of nitroso-methylurea (NMU) possess H-ras-1 oncogenes. We have shown that each of these oncogenes becomes activated by G----A transitions, the type of mutation most frequently induced by NMU. No such mutations have been observed when similar tumors were induced by dimethylbenz(a)anthracene (DMBA), a carcinogen of undefined mutagenic specificity. These results strongly suggest that H-ras-1 oncogenes are activated by NMU during initiation of carcinogenesis. These findings represent the first identification of a cellular locus relevant to neoplasia as a target for the mutagenic properties of a chemical carcinogen.
迄今为止，在人类肿瘤中已鉴定出超过15种不同的致癌基因。其中一些致癌基因，特别是ras基因家族的那些，已发现在多种致癌物诱导的动物肿瘤系统中可重复性激活。在大鼠中，单次剂量的亚硝基甲基脲（NMU）诱导的几乎90%的乳腺癌都具有H-ras-1致癌基因。我们已经表明，这些致癌基因中的每一个都通过G→A转换而被激活，这种突变类型是NMU最常诱导的。当由二甲基苯并(a)蒽（DMBA）诱导类似肿瘤时，未观察到此类突变，DMBA是一种诱变特异性不明确的致癌物。这些结果强烈表明，H-ras-1致癌基因在致癌作用起始过程中被NMU激活。这些发现首次将与肿瘤形成相关的细胞位点鉴定为化学致癌物诱变特性的靶点。
