INTERACTIONS OF NICKEL(II) WITH HISTONES - ENHANCEMENT OF 2'-DEOXYGUANOSINE OXIDATION BY NI(II) COMPLEXES WITH CH3CO-CYS-ALA-ILE-HIS-NH2, APUTATIVE METAL-BINDING SEQUENCE OF HISTONE H3

Studies of 2'-deoxyguanosine oxidation by hydrogen peroxide in the pre sence of CH3CO-Cys-Ala-Ile-His-NH2 (CAIH) and/or NiCl2 have been carri ed out in 100 mM phosphate buffer (pH 7.4) at 37 degrees C. The dimeri c CAIH oxidation product, CAIH disulfide, and its weak, octahedral Ni( II) complex, rather than the monomeric CAIH and its strong, square-pla nar Ni(II) complex, were found to be major catalysts of 8-oxo-2'-deoxy guanosine (8-oxo-dG) formation, The presence of Ni(II) largely enhance d 8-oxo-dG yield, especially at submillimolar concentrations of H2O2. The reaction was found not to involve detectable amounts of free radic als or Ni(III). These results, together with those published previousl y [Bal, W. et al, (1995) Chem. Res. Toxicol. 8, 683-692], lay a framew ork for the detailed investigations of the interactions of histone oct amer with Ni(II) and other metal ions. They also suggest that molecula r mechanisms of nickel carcinogenesis may involve oxidative damage pro cesses catalyzed by weak Ni(II) complexes with cellular components.