致癌物是诱变剂：一种将用于活化的肝脏匀浆和用于检测的细菌相结合的简单测试系统。
Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection.
作者信息
Ames B N, Durston W E, Yamasaki E, Lee F D
出版信息
Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281-5. doi: 10.1073/pnas.70.8.2281.
Abstract
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.
摘要
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。
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Toxic liver injury and carcinogenesis. Methylation of rat-liver nucleic acids by dimethylnitrosamine in vivo.毒性肝损伤与致癌作用。二甲基亚硝胺在体内对大鼠肝脏核酸的甲基化作用。
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Frameshift mutations and the genetic code. This paper is dedicated to Professor Theodosius Dobzhansky on the occasion of his 66th birthday.移码突变与遗传密码。本文谨献给西奥多修斯·杜布赞斯基教授，以庆祝他66岁生日。
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Oxidation and protein binding of aromatic amines by rat liver microsomes.大鼠肝脏微粒体对芳香胺的氧化及蛋白质结合作用。
Chem Biol Interact. 1971 Oct;3(5):321-36. doi: 10.1016/0009-2797(71)90012-3.
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A microbial assay for detecting chemical mutagens in tissue homogenates.一种用于检测组织匀浆中化学诱变剂的微生物测定法。
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Rapid detection of mutagens and carcinogens.诱变剂和致癌物的快速检测
Cancer Res. 1971 Jul;31(7):970-3.
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10
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