Kasprzak K S, North S L, Hernandez L
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702.
Chem Biol Interact. 1992 Sep 14;84(1):11-9. doi: 10.1016/0009-2797(92)90117-4.
Effects of ethanol (EtOH), mannitol (Man), L-histidine (His) and glutathione (GSH) on the oxidation of 2'-deoxyguanosine (dG) to its 8-hydroxy derivative (8-OH-dG) with H2O2 plus L-ascorbic acid (Ascb) in the absence and presence of Ni(II) were investigated in order to unveil the nature of active oxygen species involved in that oxidation. In the absence of Ni(II), production of 8-OH-dG was inhibited by His much greater than GSH greater than or equal to GSSG (oxidized glutathione) much greater than EtOH, but not by Man. The latter tended to enhance the production of 8-OH-dG. In the presence of Ni(II), the inhibition by His, GSH and GSSG, but not EtOH, was prevented. The results indicate involvement of a 'crypto-hydroxyl' radical as the dG oxidizing species in both the absence and presence of Ni(II). Also, the results provide evidence that Ni(II) complexes with His, GSH and GSSG may lack antioxidant capacity. Moreover, the Ni(II) complex with His was found capable of enhancing 8-OH-dG production by the Ascb+H2O2 system to a greater extent than Ni(II) alone. Likewise, although to a lesser extent, the formation of 8-OH-dG was enhanced by the combination of Ni(II) and Man which do not form complexes at pH 7.4. Since His is a major Ni(II) carrier in animal tissues, the dG oxidation enhancing capacity of the Ni(II) complex with His may contribute to the toxic and carcinogenic effects of Ni(II).
研究了乙醇（EtOH）、甘露醇（Man）、L-组氨酸（His）和谷胱甘肽（GSH）在有无Ni(II)存在的情况下，对2'-脱氧鸟苷（dG）与过氧化氢加L-抗坏血酸（Ascb）反应生成其8-羟基衍生物（8-OH-dG）的氧化作用，以揭示参与该氧化反应的活性氧物种的性质。在没有Ni(II)的情况下，8-OH-dG的生成受到His的抑制作用远大于GSH大于或等于氧化型谷胱甘肽（GSSG）远大于EtOH，但不受Man的抑制。后者倾向于增强8-OH-dG的生成。在有Ni(II)存在的情况下，His、GSH和GSSG的抑制作用（但EtOH的抑制作用不受影响）被消除。结果表明，在有无Ni(II)的情况下，均有一个“隐羟基”自由基作为dG氧化物种参与反应。此外，结果还证明Ni(II)与His、GSH和GSSG形成的络合物可能缺乏抗氧化能力。而且，发现Ni(II)与His形成的络合物比单独的Ni(II)更能增强Ascb+H2O2体系中8-OH-dG的生成。同样，虽然程度较小，但Ni(II)和Man的组合（在pH 7.4时不形成络合物）也能增强8-OH-dG的形成。由于His是动物组织中主要的Ni(II)载体，Ni(II)与His形成的络合物增强dG氧化的能力可能导致Ni(II)的毒性和致癌作用。
