Effect of nickel(II) and tetraglycine on hydroxylation of the guanine moiety in 2'-deoxyguanosine, DNA, and nucleohistone by hydrogen peroxide.
The purpose of this study was to determine whether the Ni(II)-tetraglycine complex system (NiG4) that is known to disproportionate H2O2 at pH > or = 8 can catalyze oxidation of the guanine residues in 2'-deoxyguanosine (dG), calf thymus DNA, and calf thymus nucleohistone (NH) by H2O2 at physiological pH. Incubation of dG with H2O2 in the presence of NiG4 at 37 degrees C, produced two effects: (a) formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and (b) decomposition of dG to 2,6-diamino-4-hydroxy-5-formamidopyrimidine and several low molecular weight unidentified products. The magnitude of both effects depended on incubation time (1-48 h), H2O2 concentration (7.5-40 mM), NiG4 concentration (0.1 or 1 mM), and pH (6.0-8.0). The effects were not detected below pH 6 and above pH 8.0. For 0.1 mM NiG4 and 7.5 mM H2O2, production of 8-OH-dG from dG (0.75 mM) during 24 h at 37 degrees C was significantly lower than from NH (1 mg/ml) or DNA (0.5 mg/ml), indicating possible specific effects that might be related to the strength of interaction of NiG4 with dG, NH, or DNA. The results indicate production of hydroxyl radical or other oxidizing species in the reaction of H2O2 with NiG4 at pH 7-8. Reactions like this may be relevant to the mechanisms of Ni(II)-mediated oxidative damage, observed in vitro and in vivo, which may contribute to the toxic and carcinogenic effects of this metal.
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201.
A K
AK
Datta
S L
SL
North
K S
KS
Kasprzak
D000818:Animals; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation / Q000187:drug effects; D009532:Nickel / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D013997:Time Factors
D006657:Histones; D009842:Oligopeptides; D006147:Guanine; D009532:Nickel; D004247:DNA; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine; C046274:glycyl-glycyl-glycyl-glycine