Interactions of nickel(II) with histones: enhancement of 2'-deoxyguanosine oxidation by Ni(II) complexes with CH3CO-Cys-Ala-Ile-His-NH2, a putative metal binding sequence of histone H3.
Studies of 2'-deoxyguanosine oxidation by hydrogen peroxide in the presence of CH3CO-Cys-Ala-Ile-His-NH2 (CAIH) and/or NiCl2 have been carried out in 100 mM phosphate buffer (pH 7.4) at 37 degrees C. The dimeric CAIH oxidation product, CAIH disulfide, and its weak, octahedral Ni(II) complex, rather than the monomeric CAIH and its strong, square-planar Ni(II) complex, were found to be major catalysts of 8-oxo-2'-deoxyguanosine (8-oxo-dG) formation. The presence of Ni(II) largely enhanced 8-oxo-dG yield, especially at submillimolar concentrations of H2O2. The reaction was found not to involve detectable amounts of free radicals or Ni(III). These results, together with those published previously [Bal, W. et al. (1995) Chem. Res. Toxicol. 8, 683-692], lay a framework for the detailed investigations of the interactions of histone octamer with Ni(II) and other metal ions. They also suggest that molecular mechanisms of nickel carcinogenesis may involve oxidative damage processes catalyzed by weak Ni(II) complexes with cellular components.
Bal
W
W
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702, USA.
Lukszo
J
J
Kasprazak
K S
KS
D018736:DNA Adducts / Q000494:pharmacology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D009532:Nickel / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010710:Phosphates / Q000494:pharmacology
D018736:DNA Adducts; D006657:Histones; D010710:Phosphates; D009532:Nickel; D003849:Deoxyguanosine