Generation of Guanine-Thymine Cross-Links in Human Cells by One-Electron Oxidation Mechanisms.

Generation of Guanine-Thymine Cross-Links in Human Cells by One-Electron Oxidation Mechanisms.
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通过单电子氧化机制在人体细胞中产生鸟嘌呤-胸腺嘧啶交联。

DOI:
10.1021/tx400158g
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发表时间:
2013
影响因子:
4.1
通讯作者:
Shafirovich,Vladimir
Shafirovich,Vladimir
中科院分区:
医学3区
文献类型:
--
作者:
Madugundu,GuruS;Wagner,JRichard;Cadet,Jean;Kropachev,Konstantin;Yun,ByeongHwa;Geacintov,NicholasE;Shafirovich,Vladimir

文献摘要

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在培养的人HeLa细胞中,由强烈的纳秒266 nm激光脉冲照射引发的细胞DNA的单电子氧化在鸟嘌呤和胸腺嘧啶碱基(G*-T*)之间产生交联,其特征在于C8鸟嘌呤(G*)和N3胸腺嘧啶(T*)原子之间的共价键。采用同位素稀释LC-MS/MS方法,以同位素标记的[15 N,13 C]-核苷酸作为内标,在多反应监测模式下定量DNA损伤。在几种已知的嘧啶和8-氧代-7,8-二氢鸟嘌呤损伤中,在50和280 mJ/cm 2/pulse的激光强度下,分别检测到每106个DNA碱基有约0.21和1.19 d(G*-T*)损伤的G*-T* 交联损伤。
The one-electron oxidation of cellular DNA in cultured human HeLa cells initiated by intense nanosecond 266 nm laser pulse irradiation produces cross-links between guanine and thymine bases (G*-T*), characterized by a covalent bond between C8 guanine (G*) and N3 thymine (T*) atoms. The DNA lesions were quantified by isotope dilution LC-MS/MS methods in the multiple reaction-monitoring mode using isotopically labeled [15N,13C]-nucleotides as internal standards. Among several known pyrimidine and 8-oxo-7,8-dihydroguanine lesions, the G*-T* cross-linked lesions were detected at levels of ∼0.21 and 1.19 d(G*-T*) lesions per 106DNA bases at laser intensities of 50 and 280 mJ/cm2/pulse, respectively.