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PMID: 4151811 Published · ppublish English Journal Article

Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection.

Ames BN, Durston WE, Yamasaki E, Lee FD

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.

MeSH Terms
Aflatoxins/pharmacology Aminopyrine/pharmacology Animals Anthracenes/pharmacology Base Sequence Benzopyrenes/pharmacology Biological Assay Biphenyl Compounds/pharmacology Carcinogens/pharmacology DNA, Bacterial Fluorenes/pharmacology Humans Male Methylcholanthrene/pharmacology Microsomes, Liver/enzymology Mutagens/pharmacology Mutation/drug effects NADP Rats Salmonella typhimurium/drug effects Stilbenes/pharmacology
Chemicals
Aflatoxins Anthracenes Benzopyrenes Biphenyl Compounds Carcinogens DNA, Bacterial Fluorenes Mutagens Stilbenes Aminopyrine NADP Methylcholanthrene
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ames B N
Durston W E
Yamasaki E
Lee F D
References (17)
17 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1973-08-00
Pages
2281-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC433718
Subset
IM
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