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铁介导的过氧化氢和超氧阴离子诱导的姐妹染色单体交换

Iron-mediated induction of sister-chromatid exchanges by hydrogen peroxide and superoxide anion.

作者信息

Larramendy M, Mello-Filho A C, Martins E A, Meneghini R

出版信息

Mutat Res. 1987 May;178(1):57-63. doi: 10.1016/0027-5107(87)90086-8.

DOI:10.1016/0027-5107(87)90086-8
PMID:3033488
Abstract

When Chinese hamster fibroblasts were exposed to hydrogen peroxide or to a system consisting of xanthine oxidase and hypoxanthine, which generates superoxide anion plus hydrogen peroxide, sister-chromatid exchanges (SCEs) were formed in a dose-dependent manner. When the iron-complexing agent o-phenanthroline was present in the medium, however, the production of these SCEs was completely inhibited. This fact indicates that the Fenton reaction: Fe2+ + H2O2----OH0 + OH- + Fe3+ is responsible for the production of SCEs. When O2- and H2O2 were generated inside the cell by incubation with menadione, the production of SCE was prevented by co-incubation with copper diisopropylsalicylate, a superoxide dismutase mimetic agent. The most likely role of O2- is as a reducing agent of Fe3+: O2- + Fe3+----Fe2+ + O2, so that the sum of this and the Fenton reaction, i.e., the iron-catalyzed Haber-Weiss reaction, provides an explanation for the active oxygen species-induced SCE: H2O2 + O2(-)----OH- + OH0 + O2. According to this view, the OH radical thus produced is the agent which ultimately causes SCE. These results are discussed in comparison with other mechanisms previously proposed for induction of SCE by active oxygen species.

摘要

当中国仓鼠成纤维细胞暴露于过氧化氢或由黄嘌呤氧化酶和次黄嘌呤组成的体系(该体系产生超氧阴离子加过氧化氢)时,姐妹染色单体交换(SCEs)以剂量依赖的方式形成。然而,当培养基中存在铁络合剂邻菲罗啉时,这些SCEs的产生被完全抑制。这一事实表明,芬顿反应:Fe2+ + H2O2→OH• + OH- + Fe3+ 是SCEs产生的原因。当通过与甲萘醌孵育在细胞内产生O2-和H2O2时,与超氧化物歧化酶模拟剂二异丙基水杨酸铜共同孵育可防止SCE的产生。O2-最可能的作用是作为Fe3+的还原剂:O2- + Fe3+→Fe2+ + O2,因此,这一反应与芬顿反应的总和,即铁催化的哈伯-维伊斯反应,为活性氧诱导的SCE提供了解释:H2O2 + O2-→OH- + OH• + O2。根据这一观点,由此产生的OH自由基是最终导致SCE的介质。将这些结果与先前提出的活性氧诱导SCE的其他机制进行了比较讨论。

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Iron-mediated induction of sister-chromatid exchanges by hydrogen peroxide and superoxide anion.铁介导的过氧化氢和超氧阴离子诱导的姐妹染色单体交换
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Biochem J. 1988 Dec 1;256(2):475-9. doi: 10.1042/bj2560475.
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Oxidation of DNA bases by tumor promoter-activated processes.肿瘤启动子激活过程导致的DNA碱基氧化。
Environ Health Perspect. 1989 May;81:45-54. doi: 10.1289/ehp.898145.
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Hydrogen peroxide cytotoxicity. Low-temperature enhancement by ascorbate or reduced lipoate.过氧化氢细胞毒性。抗坏血酸或还原型硫辛酸对其低温增强作用。
Biochem J. 1989 Dec 15;264(3):651-5. doi: 10.1042/bj2640651.
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Mutagenesis by the autoxidation of iron with isolated DNA.铁与分离的DNA自氧化引发的诱变作用。
Proc Natl Acad Sci U S A. 1988 Jun;85(11):3918-22. doi: 10.1073/pnas.85.11.3918.
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Effects of metal ion chelators on DNA strand breaks and inactivation produced by hydrogen peroxide in Escherichia coli: detection of iron-independent lesions.金属离子螯合剂对过氧化氢在大肠杆菌中产生的DNA链断裂和失活的影响:铁非依赖性损伤的检测
J Bacteriol. 1991 Apr;173(8):2562-8. doi: 10.1128/jb.173.8.2562-2568.1991.
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