Fe2+, Fe3+, and oxygen react with DNA-derived radicals formed during iron-mediated fenton reactions
Fe2+, Fe3+, and oxygen react with DNA-derived radicals formed during iron-mediated fenton reactions
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DOI：
10.1021/bi961235j
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发表时间：
1996-09-17
期刊：
影响因子：
2.9
通讯作者：
Linn, S
中科院分区：
文献类型：
--
作者：
Henle, ES;Luo, YZ;Linn, S
当 H2O2 过量时，Fe2+ 介导的 Fenton 反应中 O-2 的存在会减少氧化 DNA 损伤。在这些反应过程中，在厌氧条件下，DNA 的存在相对于 Fe2+ 消耗增加了 H2O2 消耗，但在有氧条件下相对于 Fe2+ 消耗减少了 H2O2 消耗。然而，两种条件下 H2O2 消耗的伪双分子速率常数相同，表明 DNA 的存在影响铁库的氧化和/或还原。为了了解这些效应的基础，用乙醇代替 DNA 作为模型化合物。 Fe2+ 和 H2O2 消耗的计算机模拟经过实验验证，并可以识别导致化学计量变化的主要反应。基于这些结果以及有氧和厌氧条件下 DNA 损伤的定性和定量差异，得出的结论是，在 DNA 存在的情况下，Fe3+ 会被一些 DNA 自由基还原。然而，如果存在 O-2，这些自由基会与 O-2 发生反应，并且这些反应的产物可以氧化 Fe2+。在暴露于 Fe 和 H2O2 后，O-2 改变含 dC 和 dG 底物的产物的机制符合这些一般方案。提供了电离辐射引起的 DNA 损伤和芬顿反应引起的 DNA 损伤之间的另一个区别。
Oxidative DNA damage is decreased by the presence of O-2 during Fe2+-mediated Fenton reactions when H2O2 is in excess. During these reactions, the presence of DNA increases H2O2 consumption relative to Fe2+ consumption under anaerobic conditions, but decreases H2O2 consumption relative to Fe2+ consumption under aerobic conditions, The pseudobimolecular rate constant of H2O2 consumption is the same under both conditions, however, indicating that the presence of DNA affects the oxidation and/or reduction of the iron pool. To understand the basis of these effects, DNA was replaced with ethanol as a model compound. Computer simulations of Fe2+ and H2O2 consumption were experimentally verified and allowed identification of the predominant reactions leading to the changes in stoichiometry. Based upon these results and upon qualitative and quantitative differences in DNA damages between aerobic and anaerobic conditions, it was concluded that, in the presence of DNA, Fe3+ is reduced by some DNA radicals. However, if O-2 is present, these radicals react instead with O-2 and the product of these reactions can then oxidize Fe2+. Mechanisms proposed for the alteration by O-2 of products from dC- and dG-containing substrates after exposure to Fe and H2O2 fit these general schemes. provide another distinction between DNA damage caused by ionizing radiation and that caused by Fenton reactions.