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Potent DNA damage by polyhalogenated quinones and H2O2 via a metal-independent and Intercalation-enhanced oxidation mechanism Public Deposited

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  • Potent DNA damage by polyhalogenated quinones and H[subscript 2]O[subscript 2] via a metal-independent and Intercalation-enhanced oxidation mechanism
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  • Polyhalogenated quinones are a class of carcinogenic intermediates. We found recently that the highly reactive and biologically/environmentally important center [dot]OH can be produced by polyhalogenated quinones and H₂O₂ independent of transition metal ions. However, it is not clear whether this unusual metal-independent center dot OH producing system can induce potent oxidative DNA damage. Here we show that TCBQ and H₂O₂ 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 center dot OH generation more adjacent to DNA. This is the first report that polyhalogenated quinoid carcinogens and H₂O₂ 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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  • Yin, R., Zhang, D., Song, Y., Zhu, B., & Wang, H. (2013). Potent DNA damage by polyhalogenated quinones and H(2)O(2) via a metal-independent and intercalation-enhanced oxidation mechanism. Scientific Reports, 3, 1269. doi: 10.1038/srep01269
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  • 3
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  • This work was supported by the grants from the National Natural Science Foundation ofChina (21077129, 20877091, 20890112, 21125523, 20925724, 21237005 and 20921063) andthe National Basic Research Program of China (2009CB421605 and 2010CB933502) toDr. Wang and Dr. Zhu.
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