Carcinogens are Mutagens: A Simple Test System Combining Liver Homogenates for Activation and Bacteria for Detection

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 stacki...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1973-08, Vol.70 (8), p.2281-2285
Hauptverfasser: Ames, Bruce N., Durston, William E., Yamasaki, Edith, Lee, Frank D.
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Sprache:eng
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Zusammenfassung: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 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.70.8.2281