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Potent DNA damage by polyhalogenated quinones and H(2)O(2) via a metal-independent and Intercalation-enhanced oxidation mechanism
Polyhalogenated quinones are a class of carcinogenic intermediates. We found recently that the highly reactive and biologically/environmentally important ·OH can be produced by polyhalogenated quinones and H(2)O(2) independent of transition metal ions. However, it is not clear whether this unusual m...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572447/ https://www.ncbi.nlm.nih.gov/pubmed/23429247 http://dx.doi.org/10.1038/srep01269 |
Sumario: | Polyhalogenated quinones are a class of carcinogenic intermediates. We found recently that the highly reactive and biologically/environmentally important ·OH can be produced by polyhalogenated quinones and H(2)O(2) independent of transition metal ions. However, it is not clear whether this unusual metal-independent ·OH producing system can induce potent oxidative DNA damage. Here we show that TCBQ and H(2)O(2) can induce oxidative damage to both dG and dsDNA; but surprisingly, it was more efficient to induce oxidative damage in dsDNA than in dG. We found that this is probably due to its strong intercalating ability to dsDNA through competitive intercalation assays. The intercalation of TCBQ in dsDNA may lead to ·OH generation more adjacent to DNA. This is the first report that polyhalogenated quinoid carcinogens and H(2)O(2) can induce potent DNA damage via a metal-independent and intercalation-enhanced oxidation mechanism, which may partly explain their potential genotoxicity, mutagenesis, and carcinogenicity. |
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