Shi X, Mao Y, Knapton A D, Ding M, Rojanasakul Y, Gannett P M, Dalal N, Liu K
Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892.
Carcinogenesis. 1994 Nov;15(11):2475-8. doi: 10.1093/carcin/15.11.2475.
Incubation of Cr(VI) with ascorbate generated Cr(V), Cr(IV) and ascorbate-derived carbon-centered alkyl radicals, as well as formyl radicals. H2O2 caused generation of hydroxyl radicals (OH) and much higher levels of Cr(V), showing that .OH can be generated via a Cr(IV)-mediated Fenton-like reaction (Cr(IV) + H2O2-->Cr(V) + .OH + OH-). 1,10-Phenanthroline and deferoxamine inhibited the formation of both .OH and Cr(V) from the reaction of Cr(VI) with ascorbate in the presence of H2O2. Electrophoretic assays showed that ascorbate-derived free radicals caused DNA double-strand breaks. .OH radicals generated by Cr(V)- and Cr(IV)-mediated Fenton-like reactions also caused DNA double-strand breaks. HPLC measurements showed that .OH radicals generated by Cr(IV) and Cr(V) from H2O2 caused 2'-deoxyguanine hydroxylation to form 8-hydroxy-2'-deoxyguanine.
六价铬（Cr(VI)）与抗坏血酸盐孵育会生成五价铬（Cr(V)）、四价铬（Cr(IV)）、抗坏血酸盐衍生的碳中心烷基自由基以及甲酰基自由基。过氧化氢（H2O2）会导致羟基自由基（OH）的生成以及更高水平的五价铬（Cr(V)），这表明羟基自由基（OH）可以通过四价铬（Cr(IV)）介导的类芬顿反应（Cr(IV) + H2O2→Cr(V) + OH + OH-）生成。1,10 - 菲咯啉和去铁胺在过氧化氢（H2O2）存在的情况下，抑制了六价铬（Cr(VI)）与抗坏血酸盐反应中羟基自由基（OH）和五价铬（Cr(V)）的形成。电泳分析表明，抗坏血酸盐衍生的自由基会导致DNA双链断裂。由五价铬（Cr(V)）和四价铬（Cr(IV)）介导的类芬顿反应产生的羟基自由基（OH）也会导致DNA双链断裂。高效液相色谱测量表明，四价铬（Cr(IV)）和五价铬（Cr(V)）与过氧化氢（H2O2）反应产生的羟基自由基（OH）会导致2'-脱氧鸟嘌呤羟基化形成8 - 羟基 - 2'-脱氧鸟嘌呤。
