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Proc Natl Acad Sci U S A. Dec 1987; 84(24): 8917–8921.
PMCID: PMC299662

Spontaneous mutagenesis and oxidative damage to DNA in Salmonella typhimurium.


Salmonella typhimurium strains containing deletions of oxyR, a positive regulator of defenses against oxidative stress, show 10- to 55-fold higher frequencies of spontaneous mutagenesis compared to otherwise isogenic oxyR+ control strains. The high spontaneous-mutation frequency in oxyR deletion strains is decreased by a factor of 3 when the strains are grown anaerobically. oxyR deletion strains show an increase in small deletion mutations and at least three of the six possible base-substitution mutations (T.A to A.T, C.G to T.A, and C.G to A.T). However, the largest increase in mutation frequency is observed for T.A to A.T transversions (40- to 146-fold), the base-substitution mutation most frequently caused by chemical oxidants. The introduction into oxyR deletion strains of multicopy plasmids carrying the oxyR-regulated genes for catalase (katG) or alkyl hydroperoxide reductase (ahp) results in overexpression of the respective enzyme activities and decreases the number of spontaneous mutants to wild-type levels. The introduction into oxyR deletions of a plasmid carrying the gene for superoxide dismutase (sodA) decreases the mutation frequency by a factor of 5 in some strain backgrounds. Strains that contain a dominant oxyR mutation and overexpress proteins regulated by oxyR show lower spontaneous-mutation frequencies by a factor of 2. These results indicate that oxyR and oxyR-regulated genes play a significant role in defense against spontaneous oxidative DNA damage. The role of oxidative damage to DNA in "spontaneous" mutagenesis is discussed.

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  • Sargentini NJ, Smith KC. Spontaneous mutagenesis: the roles of DNA repair, replication, and recombination. Mutat Res. 1985 Jul;154(1):1–27. [PubMed]
  • Fridovich I. The biology of oxygen radicals. Science. 1978 Sep 8;201(4359):875–880. [PubMed]
  • Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev. 1979 Jul;59(3):527–605. [PubMed]
  • Ames BN. Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science. 1983 Sep 23;221(4617):1256–1264. [PubMed]
  • Cathcart R, Schwiers E, Saul RL, Ames BN. Thymine glycol and thymidine glycol in human and rat urine: a possible assay for oxidative DNA damage. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5633–5637. [PMC free article] [PubMed]
  • Hartman Z, Hartman PE, Barnes WM, Tuley E. Spontaneous mutation frequencies in Salmonella: enhancement of G/C to A/T transitions and depression of deletion and frameshift mutation frequencies afforded by anoxic incubation. Environ Mutagen. 1984;6(5):633–650. [PubMed]
  • Farr SB, D'Ari R, Touati D. Oxygen-dependent mutagenesis in Escherichia coli lacking superoxide dismutase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8268–8272. [PMC free article] [PubMed]
  • Imlay JA, Linn S. Bimodal pattern of killing of DNA-repair-defective or anoxically grown Escherichia coli by hydrogen peroxide. J Bacteriol. 1986 May;166(2):519–527. [PMC free article] [PubMed]
  • Boling M, Adler H, Masker W. Restoration of viability to an Escherichia coli mutant deficient in the 5'----3' exonuclease of DNA polymerase I. J Bacteriol. 1984 Nov;160(2):706–710. [PMC free article] [PubMed]
  • Morimyo M. Anaerobic incubation enhances the colony formation of a polA recB strain of Escherichia coli K-12. J Bacteriol. 1982 Oct;152(1):208–214. [PMC free article] [PubMed]
  • Christman MF, Morgan RW, Jacobson FS, Ames BN. Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins in Salmonella typhimurium. Cell. 1985 Jul;41(3):753–762. [PubMed]
  • Morgan RW, Christman MF, Jacobson FS, Storz G, Ames BN. Hydrogen peroxide-inducible proteins in Salmonella typhimurium overlap with heat shock and other stress proteins. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8059–8063. [PMC free article] [PubMed]
  • Winston F, Botstein D, Miller JH. Characterization of amber and ochre suppressors in Salmonella typhimurium. J Bacteriol. 1979 Jan;137(1):433–439. [PMC free article] [PubMed]
  • Anderson RP, Roth JR. Tandem chromosomal duplications in Salmonella typhimurium: fusion of histidine genes to novel promoters. J Mol Biol. 1978 Feb 15;119(1):147–166. [PubMed]
  • Touati D. Cloning and mapping of the manganese superoxide dismutase gene (sodA) of Escherichia coli K-12. J Bacteriol. 1983 Sep;155(3):1078–1087. [PMC free article] [PubMed]
  • Triggs-Raine BL, Loewen PC. Physical characterization of katG, encoding catalase HPI of Escherichia coli. Gene. 1987;52(2-3):121–128. [PubMed]
  • Maron DM, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutat Res. 1983 May;113(3-4):173–215. [PubMed]
  • VOGEL HJ, BONNER DM. Acetylornithinase of Escherichia coli: partial purification and some properties. J Biol Chem. 1956 Jan;218(1):97–106. [PubMed]
  • Levin DE, Ames BN. Classifying mutagens as to their specificity in causing the six possible transitions and transversions: a simple analysis using the Salmonella mutagenicity assay. Environ Mutagen. 1986;8(1):9–28. [PubMed]
  • Levin DE, Hollstein M, Christman MF, Schwiers EA, Ames BN. A new Salmonella tester strain (TA102) with A X T base pairs at the site of mutation detects oxidative mutagens. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7445–7449. [PMC free article] [PubMed]
  • Walker GC. Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli. Microbiol Rev. 1984 Mar;48(1):60–93. [PMC free article] [PubMed]
  • Hoffman PS, Pine L, Bell S. Production of superoxide and hydrogen peroxide in medium used to culture Legionella pneumophila: catalytic decomposition by charcoal. Appl Environ Microbiol. 1983 Mar;45(3):784–791. [PMC free article] [PubMed]
  • Levin DE, Marnett LJ, Ames BN. Spontaneous and mutagen-induced deletions: mechanistic studies in Salmonella tester strain TA102. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4457–4461. [PMC free article] [PubMed]
  • Loeb LA, Preston BD. Mutagenesis by apurinic/apyrimidinic sites. Annu Rev Genet. 1986;20:201–230. [PubMed]
  • Schaaper RM, Loeb LA. Depurination causes mutations in SOS-induced cells. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1773–1777. [PMC free article] [PubMed]
  • Schaaper RM, Glickman BW, Loeb LA. Mutagenesis resulting from depurination is an SOS process. Mutat Res. 1982 Nov;106(1):1–9. [PubMed]
  • Kunkel TA. Mutational specificity of depurination. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1494–1498. [PMC free article] [PubMed]
  • Chetsanga CJ, Grigorian C. A dose-response study on opening of imidazole ring of adenine in DNA by ionizing radiation. Int J Radiat Biol Relat Stud Phys Chem Med. 1983 Oct;44(4):321–331. [PubMed]
  • Lindahl T. DNA repair enzymes. Annu Rev Biochem. 1982;51:61–87. [PubMed]
  • Demple B, Johnson A, Fung D. Exonuclease III and endonuclease IV remove 3' blocks from DNA synthesis primers in H2O2-damaged Escherichia coli. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7731–7735. [PMC free article] [PubMed]
  • Chan E, Weiss B. Endonuclease IV of Escherichia coli is induced by paraquat. Proc Natl Acad Sci U S A. 1987 May;84(10):3189–3193. [PMC free article] [PubMed]

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