Identification of Ultimate DNA Damaging Oxygen Species

DNA damage induced by various reactive oxygen species can be characterized using a set of repair endonucleases with defined substrate specificities. DNA damage profiles thus obtained in a cell-free system can be compared with those observed in cellular DNA. Using this approach, we have demonstrated...

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Bibliographic Details
Published inEnvironmental health perspectives Vol. 88; pp. 111 - 115
Main Authors Epe, Bernd, Hegler, Jutta, Wild, Dieter
Format Journal Article
LanguageEnglish
Published United States National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare 01.08.1990
Subjects
Cell-Free System
DNA Damage
DNA Repair
Enzymes
Free Radicals
Hydroxyl radicals
Light
Macromolecular/Cellular Targets of Cancel Risk Factors
Mutagenicity
Mutagenicity Tests
Mutagens
Oxygen
Oxygen - pharmacology
Peroxides - pharmacology
Reactive oxygen species
Salmonella typhimurium
Salmonella typhimurium - drug effects
Singlet oxygen
Superoxides
tert-Butylhydroperoxide
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Summary:DNA damage induced by various reactive oxygen species can be characterized using a set of repair endonucleases with defined substrate specificities. DNA damage profiles thus obtained in a cell-free system can be compared with those observed in cellular DNA. Using this approach, we have demonstrated that an illumination of Salmonella typhimurium cells with visible light in the presence of methylene blue gives rise to a DNA damage profile very similar to that of singlet oxygen in a cell-free system. Therefore, the genotoxicity observed under these conditions most probably is attributable to the direct action of this species. The damage consists mainly of base modifications that are subject to repair by uvrABC-independent pathways. Revertant frequencies observed in parallel in the strains TA100 and TA2638 indicate a pronounced mutagenicity of the lesions induced. Exposure of Salmonella typhimurium to tert-butylhydroperoxide gives rise to another form of damage profile that is also different from that produced by hydroxyl radicals in a cell-free system. However, the latter dissimilarity does not exclude hydroxyl radicals as ultimate reactive species, as a very rapid repair of the induced base modifications is observed, which might have distorted the damage profile despite immediate work up.
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ISSN:0091-6765
1552-9924
DOI:10.1289/ehp.9088111