McCann J, Ames B N
Proc Natl Acad Sci U S A. 1976 Mar;73(3):950-4. doi: 10.1073/pnas.73.3.950.
About 300 carcinogens and non-carcinogens of a wide variety of chemical types have been tested for mutagenicity in the simple Salmonella/microsome test. The test uses bacteria as sensitive indicators of DNA damage, and mammalian liver extracts for metabolic conversion of carcinogens to their active mutagenic forms. There is a high correlation between carcinogenicity and mutagenicity: 90% (157/175) of the carcinogens were mutagenic in the test, including almost all of the known human carcinogens that were tested. Despite the severe limitations inherent in defining non-carcinogenicity, few "non-carcinogens" showed any degree of mutagenicity [McCann et al. (1975) Proc. Nat. Acad. Sci. USA 72, 5135-5139]. In the present paper, carcinogens negative in the test andapparent false positives are discussed. We also discuss evidence that chemical carcinogens and radiation, likely to initiate most human cancer and genetic defects do so by damage to DNA. The Salmonella test can play a central role in a program of prevention: to identify mutagenic chemicals in the environment (all indications are there are many) and to aid in the development of non-mutagenic products to prevent future human exposure.
大约300种各种化学类型的致癌物和非致癌物已在简单的沙门氏菌/微粒体试验中进行了致突变性测试。该试验使用细菌作为DNA损伤的敏感指标,并使用哺乳动物肝脏提取物将致癌物代谢转化为其活性诱变形式。致癌性和致突变性之间存在高度相关性:90%(157/175)的致癌物在试验中具有致突变性,包括几乎所有经过测试的已知人类致癌物。尽管在定义非致癌性方面存在固有的严重局限性,但很少有“非致癌物”表现出任何程度的致突变性[麦肯等人(1975年)《美国国家科学院院刊》72,5135 - 5139]。在本文中,讨论了试验中呈阴性的致癌物和明显的假阳性。我们还讨论了化学致癌物和辐射可能通过损伤DNA引发大多数人类癌症和遗传缺陷的证据。沙门氏菌试验可以在预防计划中发挥核心作用:识别环境中的诱变化学物质(所有迹象表明有很多),并帮助开发非诱变产品以防止未来人类接触。