Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection.
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.
D000348:Aflatoxins / Q000494:pharmacology; D000632:Aminopyrine / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001483:Base Sequence; D001580:Benzopyrenes / Q000494:pharmacology; D001681:Biological Assay; D001713:Biphenyl Compounds / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D004269:DNA, Bacterial; D005449:Fluorenes / Q000494:pharmacology; D006801:Humans; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation / Q000187:drug effects; D009249:NADP; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology
D000348:Aflatoxins; D000873:Anthracenes; D001580:Benzopyrenes; D001713:Biphenyl Compounds; D002273:Carcinogens; D004269:DNA, Bacterial; D005449:Fluorenes; D009153:Mutagens; D013267:Stilbenes; D000632:Aminopyrine; D009249:NADP; D008748:Methylcholanthrene