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

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.