CARCINOGENS ARE MUTAGENS - SIMPLE TEST SYSTEM COMBINING LIVER HOMOGENATES FOR ACTIVATION AND BACTERIA FOR DETECTION
CARCINOGENS ARE MUTAGENS - SIMPLE TEST SYSTEM COMBINING LIVER HOMOGENATES FOR ACTIVATION AND BACTERIA FOR DETECTION
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DOI：
10.1073/pnas.70.8.2281
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发表时间：
1973-01-01
影响因子：
11.1
通讯作者：
LEE, FD
中科院分区：
文献类型：
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作者：
AMES, BN;DURSTON, WE;LEE, FD
18 种致癌物质，包括黄曲霉毒素 B1、苯并(a)芘、乙酰氨基芴、联苯胺和二甲氨基反式二苯乙烯，可被肝匀浆激活，形成有效的移码诱变剂。我们认为，这些致癌物共同具有一个足够平坦的环系统，用于与 DNA 碱基对堆积相互作用，并且分子的一部分能够代谢为反应基团：这些结构特征是根据移码诱变理论进行讨论的。我们认为这些致癌物以及许多其他诱变剂通过体细胞突变引起癌症。描述了一种简单、廉价且极其灵敏的检测致癌物（如诱变剂）的测试。它包括使用大鼠或人肝脏匀浆进行致癌物激活（从而提供哺乳动物代谢）和一组用于诱变剂检测的沙门氏菌组氨酸突变体。匀浆、细菌和 TPNH 生成系统都在培养皿上一起孵育。对于最活跃的化合物，可以检测到少至几纳克的化合物。
18 Carcinogens, including aflatoxin B1, 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 ofSalmonellahistidine 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.