Oxidative DNA damage following photoexcitation of daunomycin: Direct role of oxygen
Oxidative DNA damage following photoexcitation of daunomycin: Direct role of oxygen
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DOI：
10.1016/j.jphotochem.2008.03.009
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发表时间：
2008-08-15
影响因子：
4.3
通讯作者：
Zewail-Foote, Maha
中科院分区：
文献类型：
--
作者：
Kainthla, Radhika;Zewail-Foote, Maha
报道了柔红霉素-DNA络合物的光活化化学，并阐明了其作用机理。我们定量地评估了DNA损伤的类型，如链断裂、氧化碱基和碱性位点，使用了结合DNA修复内切酶的质粒松弛分析。柔红霉素的光激发以剂量和照射时间依赖的方式导致DNA氧化损伤，并在这些条件下大量产生鸟嘌呤特定的氧化嘌呤。Ar脱气也能抑制DNA碱基氧化损伤，表明鸟嘌呤特异性损伤是由氧依赖机制引起的。此外，柔红霉素-DNA络合物的光激发导致超氧阴离子自由基的形成。通过对实际生成产物的研究，我们得出结论：电荷转移是该机理的主要驱动力。(C)2008爱思唯尔B.V.保留所有权利。
The chemistry of the photoactivation of daunomycin-DNA complexes is reported and the mechanism is elucidated. We quantitatively assessed the type of DNA damage, such as strand breaks, oxidized bases, and abasic sites, that arise using a plasmid relaxation assay coupled with DNA repair endonucleases. Photoexcitation of daunomycin leads to oxidative DNA damage in a dose-and irradiation time-dependent manner and guanine-specific oxidized purines are substantially produced under these conditions. Oxidative DNA base damage was also inhibited by argon degassing, indicating that guanine-specific damage arises from an oxygen-dependent mechanism. In addition, photoexcitation of daunomycin-DNA complexes leads to superoxide anion radical formation. From these studies of the actual product formed, we conclude that a charge transfer is a main driving force of the mechanism. (C) 2008 Elsevier B.V. All rights reserved.