Ames B N, Durston W E, Yamasaki E, Lee F D
Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281-5. doi: 10.1073/pnas.70.8.2281.
18 Carcinogens, including aflatoxin B(1), benzo(a)pyrene, acetylaminofluorene, benzidine, and dimethylamino-trans-stilbene, are shown to be activated by liver homogenates to form potent frameshift mutagens. We believe that these carcinogens have in common a ring system sufficiently planar for a stacking interaction with DNA base pairs and a part of the molecule capable of being metabolized to a reactive group: these structural features are discussed in terms of the theory of frameshift mutagenesis. We propose that these carcinogens, and many others that are mutagens, cause cancer by somatic mutation. A simple, inexpensive, and extremely sensitive test for detection of carcinogens as mutagens is described. It consists of the use of a rat or human liver homogenate for carcinogen activation (thus supplying mammalian metabolism) and a set of Salmonella histidine mutants for mutagen detection. The homogenate, bacteria, and a TPNH-generating system are all incubated together on a petri plate. With the most active compounds, as little as a few nanograms can be detected.
18种致癌物，包括黄曲霉毒素B（1）、苯并（a）芘、乙酰氨基芴、联苯胺和二甲基氨基反式芪，已被证明可被肝匀浆激活，形成强效的移码诱变剂。我们认为，这些致癌物具有共同的环状系统，其平面性足以与DNA碱基对发生堆积相互作用，并且分子的一部分能够代谢为反应性基团：这些结构特征将根据移码诱变理论进行讨论。我们提出，这些致癌物以及许多其他诱变剂通过体细胞突变致癌。本文描述了一种简单、廉价且极其灵敏的检测致癌物诱变活性的方法。该方法包括使用大鼠或人肝匀浆来激活致癌物（从而提供哺乳动物代谢），以及一组沙门氏菌组氨酸突变体来检测诱变剂。匀浆、细菌和一个产生TPNH的系统在培养皿中一起孵育。对于活性最强的化合物，低至几纳克都能被检测到。
