DNA damage via intercalation of copper complexes and activation by ascorbate and peroxides:: direct EPR evidence for hydroxyl radical formation and reaction

DNA damage via intercalation of copper complexes and activation by ascorbate and peroxides:: direct EPR evidence for hydroxyl radical formation and reaction
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DOI:
10.1039/a903403j
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发表时间:
1999-01-01
期刊:
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
影响因子:
--
通讯作者:
Whitwood, AC
Whitwood, AC
中科院分区:
其他
文献类型:
--
作者:
Gilbert, BC;Silvester, S;Whitwood, AC

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EPR谱为1,10-邻菲咯啉和2,2‘-联吡啶的铜(II)配合物与DNA的插层反应提供了直接证据。这些络合物被谷胱甘肽还原为铜(I)显然很容易,而抗坏血酸的反应要慢得多。根据EPR自旋捕获结果,(BuOOH)-Bu-t(得到(BuO.)-Bu-t)对铜(I)的再氧化在两个体系中都是快速的。在抗坏血酸存在下,铜(I)-DNA与H_2O_2反应生成HO。以及DNA衍生的自由基加合物的捕获。讨论了1,10-二氮杂菲和抗坏血酸的作用及其与DNA断裂的关系。
EPR spectroscopy provides direct evidence for the intercalation of copper(II) complexes of 1,10-phenanthroline and 2,2'-bipyridine with DNA. Reduction of these complexes to copper(I) by glutathione is evidently facile, whereas ascorbate reacts more slowly. Reoxidation of copper(I) with (BuOOH)-Bu-t (to give (BuO.)-Bu-t) is rapid in both systems, as judged by EPR spin-trapping results. Reaction of copper(I)-DNA with H2O2 in the presence of ascorbate leads to the generation of HO. and to the trapping of DNA-derived radical adducts. The role of 1,10-phenanthroline and ascorbate, especially, and the relevance to DNA scission, are discussed.