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. 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.
Shi
X
X
Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892.
Mao
Y
Y
Knapton
A D
AD
Ding
M
M
Rojanasakul
Y
Y
Gannett
P M
PM
Dalal
N
N
Liu
K
K
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D001205:Ascorbic Acid / Q000378:metabolism*; D002857:Chromium / Q000378:metabolism / Q000633:toxicity*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D006900:Hydroxylation
D002857:Chromium; D017665:Hydroxyl Radical; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid