title: Potent DNA damage by polyhalogenated quinones and H₂O₂ via a metal-independent and Intercalation-enhanced oxidation mechanism.
abstract: 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 H₂O₂ 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 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 ·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.
authors: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors: Ruichuan
authors: R
authors: Yin
authors: Dapeng
authors: D
authors: Zhang
authors: Yuling
authors: Y
authors: Song
authors: Ben-Zhan
authors: BZ
authors: Zhu
authors: Hailin
authors: H
authors: Wang
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry; D054879:Halogenation; D006861:Hydrogen Peroxide / Q000737:chemistry* / Q000633:toxicity; D017665:Hydroxyl Radical / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry* / Q000633:toxicity; D008670:Metals / Q000737:chemistry*; D010084:Oxidation-Reduction; D011809:Quinones / Q000737:chemistry* / Q000633:toxicity
chemical_list: D007364:Intercalating Agents; D008670:Metals; D011809:Quinones; D017665:Hydroxyl Radical; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine