Bal W, Lukszo J, Kasprazak K S
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702, USA.
Chem Res Toxicol. 1996 Mar;9(2):535-40. doi: 10.1021/tx950157i.
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.
在37℃下，于100 mM磷酸盐缓冲液（pH 7.4）中开展了在CH3CO-Cys-Ala-Ile-His-NH2（CAIH）和/或NiCl2存在的情况下，2'-脱氧鸟苷被过氧化氢氧化的研究。发现二聚体CAIH氧化产物、CAIH二硫化物及其弱八面体Ni(II)络合物，而非单体CAIH及其强平面正方形Ni(II)络合物，是8-氧代-2'-脱氧鸟苷（8-氧代-dG）形成的主要催化剂。Ni(II)的存在极大地提高了8-氧代-dG的产率，尤其是在过氧化氢亚毫摩尔浓度时。发现该反应不涉及可检测量的自由基或Ni(III)。这些结果与之前发表的结果[Bal, W.等人（1995年）《化学研究毒理学》8, 683 - 692]一起，为详细研究组蛋白八聚体与Ni(II)及其他金属离子的相互作用奠定了框架。它们还表明镍致癌的分子机制可能涉及由Ni(II)与细胞成分形成的弱络合物催化的氧化损伤过程。
