Literature DB >> 4151811

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

B N Ames, W E Durston, E Yamasaki, F D Lee.   

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.

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Year:  1973        PMID: 4151811      PMCID: PMC433718          DOI: 10.1073/pnas.70.8.2281

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  17 in total

1.  Molecular basis of a mutational hot spot in the lysozyme gene of bacteriophage T4.

Authors:  Y Okada; G Streisinger; J E Owen; J Newton; A Tsugita; M Inouye
Journal:  Nature       Date:  1972-04-14       Impact factor: 49.962

2.  Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds, and endogenous substrates. II. Role of the cytochrome P-450 and P-448 fractions in drug and steroid hydroxylations.

Authors:  A Y Lu; R Kuntzman; S West; M Jacobson; A H Conney
Journal:  J Biol Chem       Date:  1972-03-25       Impact factor: 5.157

3.  Dimethylnitrosamine: formation of mutagenic compounds by interaction with mouse liver microsomes.

Authors:  H V Malling
Journal:  Mutat Res       Date:  1971-12       Impact factor: 2.433

4.  A microbial assay for detecting chemical mutagens in tissue homogenates.

Authors:  G Ficsor; E Muthiani
Journal:  Mutat Res       Date:  1971-07       Impact factor: 2.433

5.  Rapid detection of mutagens and carcinogens.

Authors:  E E Slater; M D Anderson; H S Rosenkranz
Journal:  Cancer Res       Date:  1971-07       Impact factor: 12.701

6.  Frameshift mutagenesis in Salmonella.

Authors:  B N Ames; H J Whitfield
Journal:  Cold Spring Harb Symp Quant Biol       Date:  1966

7.  Oxidation and protein binding of aromatic amines by rat liver microsomes.

Authors:  B Beije; T Hultin
Journal:  Chem Biol Interact       Date:  1971-10       Impact factor: 5.192

8.  The effect of oral phenobarbitone on hepatic microsomal cytochrome P-450 and demethylation activity in rats fed normal and low protein diets.

Authors:  W J Marshall; A E McLean
Journal:  Biochem Pharmacol       Date:  1969-01       Impact factor: 5.858

9.  Frameshift mutations and the genetic code. This paper is dedicated to Professor Theodosius Dobzhansky on the occasion of his 66th birthday.

Authors:  G Streisinger; Y Okada; J Emrich; J Newton; A Tsugita; E Terzaghi; M Inouye
Journal:  Cold Spring Harb Symp Quant Biol       Date:  1966

10.  Epoxides of carcinogenic polycyclic hydrocarbons are frameshift mutagens.

Authors:  B N Ames; P Sims; P L Grover
Journal:  Science       Date:  1972-04-07       Impact factor: 47.728

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  255 in total

1.  Apurinic acid endonuclease activity from mouse epidermal cells.

Authors:  G Ludwig; H W Thielmann
Journal:  Nucleic Acids Res       Date:  1979-06-25       Impact factor: 16.971

2.  Mutagenicity of aflatoxin B1, activated by S-9 fractions of human, rat, mouse, rabbit, and monkey liver, towards S. typhimurium TA 98.

Authors:  K Norpoth; R Grossmeier; H Bösenberg; H Themann; M Fleischer
Journal:  Int Arch Occup Environ Health       Date:  1979-01-15       Impact factor: 3.015

Review 3.  Contributions of human enzymes in carcinogen metabolism.

Authors:  Slobodan Rendic; F Peter Guengerich
Journal:  Chem Res Toxicol       Date:  2012-05-10       Impact factor: 3.739

4.  Anticlastogenic effect of β-glucan, extracted from Saccharomyces cerevisiae, on cultured cells exposed to ultraviolet radiation.

Authors:  Ariane Fernanda da Silva; Rodrigo Juliano Oliveira; Andressa Megumi Niwa; Gláucia Fernanda Rocha D'Epiro; Lúcia Regina Ribeiro; Mário Sérgio Mantovani
Journal:  Cytotechnology       Date:  2012-06-09       Impact factor: 2.058

Review 5.  Where microbiology meets microengineering: design and applications of reporter bacteria.

Authors:  Jan Roelof van der Meer; Shimshon Belkin
Journal:  Nat Rev Microbiol       Date:  2010-07       Impact factor: 60.633

Review 6.  The risks of handling cytotoxic drugs. I. Methods of testing exposure.

Authors:  G P Kaijser; W J Underberg; J H Beijnen
Journal:  Pharm Weekbl Sci       Date:  1990-12-14

7.  Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions.

Authors:  E Eisenstadt; A J Warren; J Porter; D Atkins; J H Miller
Journal:  Proc Natl Acad Sci U S A       Date:  1982-03       Impact factor: 11.205

8.  Rutin-induced beta-glucosidase activity in Streptococcus faecium VGH-1 and Streptococcus sp. strain FRP-17 isolated from human feces: formation of the mutagen, quercetin, from rutin.

Authors:  I A MacDonald; R G Bussard; D M Hutchison; L V Holdeman
Journal:  Appl Environ Microbiol       Date:  1984-02       Impact factor: 4.792

Review 9.  Half-Intercalation Stabilizes Slipped Mispairing and Explains Genome Vulnerability to Frameshift Mutagenesis by Endogenous "Molecular Bookmarks".

Authors:  Andrei Kuzminov
Journal:  Bioessays       Date:  2019-08-05       Impact factor: 4.345

10.  Plasmid (pKM101)-mediated enhancement of repair and mutagenesis: dependence on chromosomal genes in Escherichia coli K-12.

Authors:  G C Walker
Journal:  Mol Gen Genet       Date:  1977-03-28
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