Fe2+, Fe3+, and Oxygen React with DNA-Derived Radicals Formed during Iron-Mediated Fenton Reactions
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- 作者：Ernst S. Henle ; Yongzhang Luo ; and Stuart Linn
- 刊名：Biochemistry
- 出版年：1996
- 出版时间：September 17, 1996
- 年：1996
- 卷：35
- 期：37
- 页码：12212 - 12219
- 全文大小：687K
- 年卷期：v.35,no.37(September 17, 1996)
- ISSN：1520-4995
文摘
Oxidative DNA damage is decreased by the presence ofO2 during Fe2+-mediated Fentonreactions when H2O2 is in excess. Duringthese reactions, the presence of DNA increasesH2O2 consumptionrelative to Fe2+ consumption under anaerobic conditions,but decreases H2O2 consumption relativetoFe2+ consumption under aerobic conditions. Thepseudobimolecular rate constant of H2O2consumptionis the same under both conditions, however, indicating that thepresence of DNA affects the oxidationand/or reduction of the iron pool. To understand the basis ofthese effects, DNA was replaced withethanol as a model compound. Computer simulations ofFe2+ and H2O2 consumption wereexperimentallyverified and allowed identification of the predominant reactionsleading to the changes in stoichiometry.Based upon these results and upon qualitative and quantitativedifferences in DNA damages betweenaerobic and anaerobic conditions, it was concluded that, in thepresence of DNA, Fe3+ is reduced bysome DNA radicals. However, if O2 is present, theseradicals react instead with O2 and the productofthese reactions can then oxidize Fe2+. Mechanismsproposed for the alteration by O2 of productsfromdC- and dG-containing substrates after exposure to Fe andH2O2 fit these general schemes. Theseresultsprovide another distinction between DNA damage caused by ionizingradiation and that caused by Fentonreactions.