Endogenous oxidative damage of mtDNA
Endogenous oxidative damage of mtDNA
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DOI：
10.1016/s0027-5107(99)00007-x
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发表时间：
1999-03-08
影响因子：
2.3
通讯作者：
Ames, BN
中科院分区：
文献类型：
--
作者：
Beckman, KB;Ames, BN
大约十年前，根据氧化 DNA 加合物 8-氧代-脱氧鸟苷 (oxo(8)dG) 的分析测量，据报道线粒体 DNA 比核 DNA 遭受更大的内源性氧化损伤。随后发现线粒体 DNA 的体细胞缺失发生在人类身上，并且在代谢活跃的组织中发生的程度最大，这进一步证实了线粒体 DNA 特别容易受到内源性氧化攻击的假设。由于多种原因，土地这一假设很有吸引力。然而，该假设缺乏坚实的直接支持。自从最初的测量以来，尝试重复观察线粒体 DNA 更大的氧化已经产生了一系列跨越四个数量级的测量结果。此外，该范围包括与已公布的核 DNA 值一样低的值。在过去两年左右的时间里，氧化 DNA 加合物的定量很容易出现人为氧化，这一点已经变得很明显。我们已经报道过，少量 DNA 的分析可能特别容易受到此类干扰。由于线粒体 DNA 的产量通常较低，因此在一些研究中，与少量 DNA 相关的系统伪影可能提高了线粒体 DNA 中加合物 oxo8dG 的表观水平（相对于核 DNA）。无论实验差异的原因是什么，已发表的氧化损伤测量值之间的巨大差异使得我们不可能得出线粒体 DNA 比核 DNA 遭受更大氧化的结论。然而，尽管目前存在混乱，但有理由假设情况确实如此。我们简要描述了许多工作人员正在开发的方法，这些方法可能会克服当前的障碍，并使假设得到明确的检验。 (C) 1999 Elsevier Science B.V. 保留所有权利。
Almost a decade ago, based on analytical measurements of the oxidative DNA adduct 8-oxo-deoxyguanosine (oxo(8)dG), it was reported that mitochondrial DNA suffers greater endogenous oxidative damage than nuclear DNA. The subsequent discovery that somatic deletions of mitochondrial DNA occur in humans, and that they do so to the greatest extent in metabolically active tissues, strengthened the hypothesis that mitochondrial DNA is particularly susceptible to endogenous oxidative attack. This hypothesis was land is) appealing for a number of reasons. Nevertheless, solid direct support for the hypothesis is lacking. Since the initial measurements, attempts to repeat the observation of greater oxidation of mitochondrial DNA have resulted in a range of measurements that spans over four orders of magnitude. Moreover, this range includes values that are as low as published values for nuclear DNA. In the last 2 years or so, it has become apparent that the quantification of oxidative DNA adducts is prone to artifactual oxidation. We have reported that the analysis of small quantities of DNA may be particularly susceptible to such interference. Because yields of mitochondrial DNA are generally low, a systematic artifact associated with low quantities of DNA may have elevated the apparent level of adduct oxo8dG in mitochondrial DNA relative to nuclear DNA in some studies. Whatever the cause for the experimental variation, the huge disparity between published measurements of oxidative damage makes it impossible to conclude that mitochondrial DNA suffers greater oxidation than nuclear DNA. Despite the present confusion, however, there are reasons to hypothesize that this is indeed the case. We briefly describe methods being developed by a number of workers that are likely to surmount current obstacles and allow the hypothesis to be tested definitively. (C) 1999 Elsevier Science B.V. All rights reserved.