Stanley L A
Department of Pharmacology, University of Oxford, UK.
Toxicology. 1995 Feb 27;96(3):173-94. doi: 10.1016/0300-483x(94)02991-3.
The observation that oncogenes are frequently activated in human tumours raises the question of whether these genes are involved in chemical carcinogenesis. H-ras activation is probably an initiating event in mouse skin and rat mammary gland systems. The H-ras oncogene is also important in mouse liver tumours; in mouse lung the K-ras gene is commonly activated. In both, the mutations observed are usually those predicted from the adduct-forming properties of the carcinogen. Among non-ras oncogenes, only raf and neu have been detected in experimental tumours. Tumour suppressor genes are frequently inactivated in human tumours. Searches for such phenomena in animal tumours have generally had disappointing results. p53 and Rb gene alterations are rarely observed in chemically-induced tumours. The reason may be that unknown tumour suppressor genes are involved in animal tumour development. Several novel genes have been identified using animal tumour susceptibility models. Thus, ras genes are important in chemical carcinogenesis, but as the methodology for studying other genes improves, their roles will be seen in perspective.
致癌基因在人类肿瘤中经常被激活这一现象，引发了这些基因是否参与化学致癌过程的问题。H-ras激活可能是小鼠皮肤和大鼠乳腺系统中的一个起始事件。H-ras致癌基因在小鼠肝癌中也很重要；在小鼠肺癌中，K-ras基因通常被激活。在这两种情况下，观察到的突变通常是根据致癌物的加合物形成特性预测的那些突变。在非ras致癌基因中，只有raf和neu在实验性肿瘤中被检测到。肿瘤抑制基因在人类肿瘤中经常失活。在动物肿瘤中寻找此类现象的研究通常结果令人失望。在化学诱导的肿瘤中很少观察到p53和Rb基因改变。原因可能是未知的肿瘤抑制基因参与了动物肿瘤的发展。使用动物肿瘤易感性模型已经鉴定出了几个新基因。因此，ras基因在化学致癌过程中很重要，但随着研究其他基因的方法的改进，它们的作用将得到正确看待。
