The role of metal ion binding in generating 8-hydroxy-2′-deoxyguanosine from the nucleoside 2′-deoxyguanosine and the nucleotide 2′-deoxyguanosine-5′-monophosphate
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摘要
The metal ions Cu(II), Fe(II), and Cr(III) were allowed to react with H2O2 in the presence of either the mononucleoside 2′-deoxyguanosine (dG) or the mononucleotide 2′-deoxyguanosine-5′-monophosphate (dGMP). The percentage of reacted dG or dGMP that formed the oxidative damage marker 8-hydroxy-2′-deoxyguanosine (8-OH-dG) was monitored. Oxidative damage from reactions involving Cu(II) appear dependent on an interaction between copper and N7 on the guanine base. Any interactions involving the phosphate group have little additional effect on overall oxidative damage or 8-OH-dG production. Reactions involving Fe(II) seem very dependent on an interaction that may involve both N7 on the guanine base and the phosphate group. This interaction may slow oxidation of Fe(II) to Fe(III) in solution, keeping iron in a readily available form to undergo the Fenton reaction. Chromium(III) appears to interact with the phosphate group of dGMP, resulting in significant overall oxidative damage. However, production of 8-OH-dG appears to be very dependent on the ability of Cr(III) to interact with N7 on the guanine base, an interaction that seems to be weak for both the mononucleoside and mononucleotide.

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