Ozone is a major component of air pollution and carries potentially mutagenic and harmful affects to health. The oxidation of isolated calf thymus DNA (CT-DNA) led to the nearly quantitative loss of normal DNA 2′-deoxyribonucleosides in the following order: T > G > C ≫ A. The major modification of pyrimidines (T, C, and 5-methylcytosine (5mC)) was the corresponding 5-hydroxyhydantoin derivative after complete digestion of DNA to its component 2′-deoxyribonucleosides. The oxidation of 5mC was 2.5-fold more susceptible than C considering the relative mole fraction of 5mC to C in CT-DNA. Other common oxidation products of pyrimidines (e.g., 5,6-dihydroxy-5,6-dihydropyrimidines, the so-called pyrimidine 5,6-glycols) were formed with a lower yield than 5-hydroxyhydantoin derivatives. In addition, several common oxidation products of G were observed (e.g., 8-oxo-7,8-dihydroguanine (8oxoG)) albeit with relatively minor yields. The sum of individual products was notably less than the loss of 2′-deoxyribonucleosides from which they were derived. In a search for additional products, we discovered the formation of pyrimidine ring fragments, predominantly N-formamide and N-urea, which were measured as a dinucleotide next to a nonmodified nucleotide upon partial digestion of oxidized DNA. Interestingly, the latter fragments were also observed in dinucleotides containing 8oxoG, indicating the formation of tandem lesions during ozonolysis of DNA. The oxidation of DNA upon exposure to ozone can be explained by reactions of an intermediate ozonide. These studies underline the complexity of ozone-induced DNA damage and provide valuable information to assess the formation of this damage in cellular DNA.

中文翻译：

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臭氧诱导的 DNA 损伤：氧化修饰 DNA 碱基的潘多拉魔盒

臭氧是空气污染的主要组成部分，对健康具有潜在的诱变性和有害影响。分离的小牛胸腺 DNA (CT-DNA) 的氧化导致正常 DNA 2'-脱氧核糖核苷按以下顺序几乎定量丢失：T > G > C ≫ A. 嘧啶（T、C 和 5 -甲基胞嘧啶 (5mC)) 是在 DNA 完全消化为其组分 2'-脱氧核糖核苷后相应的 5-羟基乙内酰脲衍生物。考虑到 CT-DNA 中 5mC 与 C 的相对摩尔分数，5mC 的氧化比 C 更敏感 2.5 倍。嘧啶的其他常见氧化产物（例如，5,6-二羟基-5,6-二氢嘧啶，所谓的嘧啶 5,6-二醇）的形成率低于 5-羟基乙内酰脲衍生物。此外，观察到 G 的几种常见氧化产物（例如 8-oxo-7,8-dihydroguanine (8oxoG)），尽管产量相对较低。单个产物的总和明显小于衍生它们的 2'-脱氧核糖核苷的损失。在寻找其他产品时，我们发现了嘧啶环片段的形成，主要是N -甲酰胺和N -尿素，在部分消化氧化 DNA 后，作为未修饰核苷酸旁边的二核苷酸进行测量。有趣的是，在含有 8oxoG 的二核苷酸中也观察到了后一种片段，表明在 DNA 臭氧分解过程中形成了串联损伤。暴露于臭氧时 DNA 的氧化可以通过中间体臭氧化物的反应来解释。这些研究强调了臭氧引起的 DNA 损伤的复杂性，并为评估细胞 DNA 中这种损伤的形成提供了有价值的信息。