Nickel(II)-catalysed oxidative guanine and DNA damage beyond 8-oxoguanine

Nickel(II)-catalysed oxidative guanine and DNA damage beyond 8-oxoguanine
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DOI:
10.1016/j.freeradbiomed.2007.02.025
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发表时间:
2007-06-01
影响因子:
7.4
通讯作者:
Smyth, Malcolm R.
Smyth, Malcolm R.
中科院分区:
医学1区
文献类型:
--
作者:
Kelly, Michele C.;Whitaker, Gillian;Smyth, Malcolm R.

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DNA 氧化损伤是最重要、研究最多的疾病机制之一。它与癌症、心脏病、肝炎和艾滋病毒等一系列绝症以及各种日常疾病有关。引发此类 DNA 损伤的机制有多种,包括辐射和化学氧化等;然而,这些机制尚未完全阐明。对镍 (II) 介导的 DNA 氧化进行的 HPLC-UV-EC 研究获得的结果表明,游离鸟嘌呤和 DNA 中的鸟嘌呤以不稳定、几乎振荡的方式形成 8-氧代鸟嘌呤 (8-oxoG)。当单独的 8-oxoG 处于这些条件下时,也观察到零星的 8-oxoG 浓度。 HPLC-MS/MS 研究表明,在 pH 11 时,游离鸟嘌呤会形成氧化胍乙内酰脲 (oxGH),而在 pH 5.5 时,DNA 会形成胍基乙内酰脲 (GH)。 (c) 2007 Elsevier Inc. 保留所有权利。
Oxidative DNA damage is one of the most important and most studied mechanisms of disease. It has been associated with a range of terminal diseases such as cancer, heart disease, hepatitis, and HIV, as well as with a variety of everyday ailments. There are various mechanisms by which this type of DNA damage can be initiated, through radiation and chemical oxidation, among others; however, these mechanisms have yet to be fully elucidated. A HPLC-UV-EC study of the oxidation of DNA mediated by nickel(II) obtained results that show an erratic, almost oscillatory formation of 8-oxoguanine (8-oxoG) from free guanine and from guanine in DNA. Sporadic 8-oxoG concentrations were also observed when 8-oxoG alone was subjected to these conditions. A HPLC-MS/MS study showed the fort-nation of oxidised-guanidinohydantoin (oxGH) from free guanine at pH 11, and the formation of guanidinohydantoin (GH) from DNA at pH 5.5. (c) 2007 Elsevier Inc. All rights reserved.