Reid T M, Loeb L A
Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington School of Medicine, Seattle 98195.
Proc Natl Acad Sci U S A. 1993 May 1;90(9):3904-7. doi: 10.1073/pnas.90.9.3904.
Oxidative damage to DNA is mutagenic and thus may play a role in carcinogenesis. Because of the large number of different DNA lesions formed by oxidative species, no genetic alteration so far identified is exclusively associated with oxygen damage. Tandem double CC-->TT mutations are known to occur via UV damage to DNA and are thought to be a specific indicator of UV exposure. Using a sensitive reversion assay that can detect both single and double mutations within the same codon of the M13-encoded lacZ alpha gene, we show that treatments that produce reactive oxygen species can also produce tandem double CC-->TT mutations. The frequency at which these mutations occur is less than that for single base mutations by a factor of approximately 30. The induction of these mutations is inhibited by treatment that scavenges hydroxyl radicals. This unique mutation provides a marker of oxygen free radical-induced mutagenesis in cells that are not exposed to UV-irradiation and an indicator for assessing the involvement of oxidative damage to DNA in aging and tumor progression.
DNA的氧化损伤具有致突变性，因此可能在致癌过程中发挥作用。由于氧化物种会形成大量不同的DNA损伤，迄今为止尚未发现任何一种基因改变与氧损伤存在唯一关联。已知串联双CC→TT突变是由DNA的紫外线损伤引起的，被认为是紫外线暴露的特定指标。我们使用一种灵敏的回复突变检测方法，该方法能够检测M13编码的lacZα基因同一密码子内的单突变和双突变，结果表明，产生活性氧的处理也能产生串联双CC→TT突变。这些突变发生的频率比单碱基突变低约30倍。清除羟基自由基的处理可抑制这些突变的诱导。这种独特的突变提供了一种在未接受紫外线照射的细胞中氧自由基诱导诱变的标志物，以及一种评估DNA氧化损伤在衰老和肿瘤进展中所起作用的指标。
