Moriwaki Hiroshi, Osborne Martin R, Phillips David H
Osaka City Institute of Public Health & Environmental Sciences, 8-34, Tojo-cho, Tennoji-ku, Osaka 543-0026, Japan.
Toxicol In Vitro. 2008 Feb;22(1):36-44. doi: 10.1016/j.tiv.2007.07.011. Epub 2007 Aug 10.
The formation of 8-hydroxy-deoxyguanosine (8-OHdG) and strand breaks in DNA by Fenton-type reactions by mixtures of two of five metal ions, iron (II), cadmium (II), nickel (II), chromium (III) or copper (II), has been investigated and compared to their formation by each single metal ion. Salmon sperm DNA and pBluescript K+ plasmid were each incubated with hydrogen peroxide and metal ions. The formation of 8-OHdG declined in the Fe (II) or Cu (II) Fenton reaction upon addition of Cd (II) or Ni (II) ion. In contrast, the Fe (II) reaction upon addition of Cr (III) ion showed an additive influence on the formation of 8-OHdG. Furthermore, the Cu (II) plus Cr (III) reaction showed a synergistic effect. These influences relate to the interaction of metal ions with DNA, the potentials of the metal ions to generate activated oxygen and electron transfer between metal ions. The formation of DNA strand breaks was investigated in plasmid DNA by agarose gel electrophoresis and subsequent densitometry. The formation of DNA strand breaks in the Fe (II) or Cu (II) Fenton reaction decreased upon the addition of Ni (II) ion, as with the formation of 8-OHdG mediated by these metal ions. On the other hand, the formation of DNA strand breaks in the Fe (II) reaction decreased upon addition of Cr (III) ion, and the Cu (II) plus Cr (III) reaction did not show the synergistic influence on DNA strand breaks. These results suggest that interactions between two metal ions can influence the generation of 8-OHdG and the formation of DNA strand breaks and demonstrate that these lesions can arise by different mechanisms.
研究了铁（II）、镉（II）、镍（II）、铬（III）或铜（II）这五种金属离子中的两种混合形成的芬顿型反应在DNA中产生8-羟基脱氧鸟苷（8-OHdG）和链断裂的情况，并与每种单一金属离子的情况进行了比较。鲑鱼精DNA和pBluescript K+质粒分别与过氧化氢和金属离子一起孵育。在铁（II）或铜（II）的芬顿反应中加入镉（II）或镍（II）离子后，8-OHdG的形成减少。相反，在铁（II）反应中加入铬（III）离子对8-OHdG的形成有累加影响。此外，铜（II）加铬（III）反应表现出协同效应。这些影响与金属离子与DNA的相互作用、金属离子产生活性氧的电位以及金属离子之间的电子转移有关。通过琼脂糖凝胶电泳和随后的光密度测定法研究了质粒DNA中DNA链断裂的形成。与这些金属离子介导的8-OHdG形成情况一样，在铁（II）或铜（II）的芬顿反应中加入镍（II）离子后，DNA链断裂的形成减少。另一方面，在铁（II）反应中加入铬（III）离子后，DNA链断裂的形成减少，并且铜（II）加铬（III）反应对DNA链断裂没有协同影响。这些结果表明，两种金属离子之间的相互作用可以影响8-OHdG的产生和DNA链断裂的形成，并证明这些损伤可能通过不同的机制产生。
