Reactive oxygen species in tumorigenesis.
Reactive oxygen species in tumorigenesis.
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发表时间：
1994-04
期刊：
影响因子：
11.2
通讯作者：
Daniel I. Feig;Thomas M. Reid;Lawrence A. Loeb
中科院分区：
文献类型：
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作者：
Daniel I. Feig;Thomas M. Reid;Lawrence A. Loeb
在这篇综述中，我们将总结最近的数据，活性氧诱导的诱变，并考虑其与人类肿瘤发生的关系。使用单链DNA模板，可以将氧自由基诱导的特定核苷酸的化学改变与DNA聚合酶复制这些改变的碱基时发生的突变类型相关联。这使我们能够确定继发于各种氧化应激的突变类型，并研究它们产生的几种机制。由活性氧引起的细菌DNA损伤导致的最常见的突变是C到T的转换。然而，这些突变不是氧自由基诱变的致病因子，因为它们是由其他遗传毒性剂以及DNA聚合酶错误引起的DNA损伤引起的。一种类型的突变，串联CC到TT双取代，已被证明是由各种系统产生的活性氧引起的，并且可以诊断这种损伤。在哺乳动物DNA聚合酶的研究中，活性氧损伤的DNA产生的突变与在大肠杆菌中观察到的不同。这些体外研究中致突变变化的多样性突出了DNA复制酶在指定活性氧产生的突变类型中的作用。总之，我们将考虑活性氧在三种常见肿瘤（肝癌、肺癌和前列腺癌）发病机制中的作用，并考虑可能使用抗氧化预防性治疗来充分减缓肿瘤发生，以防止这些癌症在患者生命周期中的临床表现。
In this review we will summarize recent data on reactive oxygen species-induced mutagenesis and consider its relationship to tumorigenesis in humans. With the use of a single-stranded DNA template it has been possible to correlate oxygen radical-induced chemical alterations at specific nucleotides with the types of mutations that occur when these altered bases are copied by DNA polymerases. This has allowed us to identify the types of mutations that occur secondary to a variety of oxidative stresses and study several of the mechanisms by which they arise. The most frequent mutations that result from reactive oxygen species-induced damage to DNA in bacteria are C to T transitions. These mutations, however, are not pathoneumonic for mutagenesis by oxygen-free radicals since they result from DNA damage caused by other genotoxic agents as well as by DNA polymerase errors. One type of mutation, a tandem CC to TT double substitution, has been shown to be induced by reactive oxygen species generated by a variety of systems and may be diagnostic for such damage. In studies with mammalian DNA polymerases, DNA damaged by reactive oxygen species yields mutations different from those observed in Escherichia coli. This diversity of mutagenic changes in these in vitro studies highlights the role of DNA replicating enzymes in specifying the types of mutations produced by reactive oxygen species. In conclusion, we will consider the role of reactive oxygen species in the pathogenesis of three common tumors, carcinoma of the liver, lung, and prostate with consideration on the possible use of antioxidant preventive therapy to slow tumorigenesis sufficiently to prevent clinical presentation of these cancers during the life span of a patient.