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© 1994 Oxford University Press

research-article

Reaction of Cr(VI) with ascorbate and hydrogen peroxide generates hydroxyl radicals and causes DNA damage: role of a Cr(IV)-mediated Fenton-like reaction

Xianglin Shi 1, Yan Mao 1, Alan D. Knapton 1, Min Ding, Yongyut Rojanasakul 3, Peter M. Gannett 3, Naresh Dalal 4 and Kejian Liu 5

1Laboratory of Experimental Pathology, National Cancer Institute Bethesda, MD 20892, Biological Response Modifiers Program, National Cancer Institute, Frederick, MD 21702
3Department of Basic Pharmaceutical Science
4Department of Chemistry West Virginia University, Morgantown, WV 26506 and Department of Radiology, Dartmouth College, Hanover, NH 03755, USA

5To whom correspondence should be addressed

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. Electro phoretic assays showed that ascorbate-derived free radicals caused DNA double-strand breaks. OH radicals generated by Cr(V)- and Cr(IV)-medlated 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'-deoxyguanlne hydroxylatlon to form 8-hydroxy-2'-deoxyguanine.


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