DNA tandem lesions containing 8-oxo-7,8-dihydroguanine and formamido residues arise from intramolecular addition of thymine peroxyl radical to guanine
DNA tandem lesions containing 8-oxo-7,8-dihydroguanine and formamido residues arise from intramolecular addition of thymine peroxyl radical to guanine
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DOI：
10.1021/tx0155909
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发表时间：
2002-03-01
影响因子：
4.1
通讯作者：
Cadet, J
中科院分区：
文献类型：
--
作者：
Douki, T;Rivière, J;Cadet, J
暴露的曝气水溶液的二核苷单磷酸轴承的嘧啶基地和鸟嘌呤残基的电离辐射导致形成8-oxo 7，8-二氢鸟嘌呤/甲酰氨基串联病变（8-oxodG/dF）。最近的证据表明，在分离的DNA中形成后一种损伤，强调了这类病变可能的生物学相关性。因此，用含有胸腺嘧啶和鸟嘌呤的二核苷单磷酸（dGpdT和dTpdG）对8-oxodG/dF的形成进行了广泛的机理研究。首先，过氧自由基诱导降解的鸟嘌呤dGpdT和dTpdG内进行了研究，以评估分子内电子转移鸟嘌呤和胸腺嘧啶过氧自由基之间的可能性。然后，一系列的串联病变的形成，涉及甲酰胺基残基，胸腺嘧啶二醇，8-oxodG，和恶唑酮内的dTpdG和dGpdT暴露于γ-辐射的充气水溶液进行监测。除了8-oxodG/dF在显着的产量导致我们提出了一个新的机制，涉及添加的胸腺嘧啶过氧自由基的鸟嘌呤部分的串联病变的形成的情况下。这得到了O-18标记实验的支持。
Exposure of aerated aqueous solutions of dinucleoside monophosphates bearing both a pyrimidine base and a guanine residue to ionizing radiation leads to the formation of 8-oxo7,8-dihydroguanine/formamido tandem lesions (8-oxodG/dF). Recent evidence for the formation of the latter damage within isolated DNA emphasized the possible biological relevance of this class of lesions. Therefore, an extensive mechanistic study of the formation of 8-oxodG/dF was carried out with thymine and guanine containing dinucleoside monophosphates (dGpdT and dTpdG). First, the peroxyl radical-induced degradation of guanine within dGpdT and dTpdG was studied in order to assess the possibility of intramolecular electron transfer between guanine and thymine peroxyl radicals. Then, the formation of a series of tandem lesions involving a formamido residue, thymine glycols, 8-oxodG, and oxazolone was monitored within aerated aqueous solutions of dTpdG and dGpdT exposed to gamma-radiation. The absence of formation of tandem lesions other than 8-oxodG/dF in significant yield led to us propose a new mechanism involving addition of the thymine peroxyl radical to the guanine moiety. This received support from O-18 labeling experiments.