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体外用过氧亚硝酸盐处理的DNA中8-硝基鸟嘌呤的形成及其通过脱嘌呤作用从DNA中快速去除。

Formation of 8-nitroguanine in DNA treated with peroxynitrite in vitro and its rapid removal from DNA by depurination.

作者信息

Yermilov V, Rubio J, Ohshima H

机构信息

Unit of Endogenous Cancer Risk Factors, International Agency for Research on Cancer, Lyon, France.

出版信息

FEBS Lett. 1995 Dec 4;376(3):207-10. doi: 10.1016/0014-5793(95)01281-6.

DOI:10.1016/0014-5793(95)01281-6
PMID:7498543
Abstract

Peroxynitrite is a strong oxidant formed by reaction of nitric oxide with superoxide in inflamed tissues. We have demonstrated that 8-nitroguanine is formed dose-dependently in calf thymus DNA incubated with low concentrations of peroxynitrite in vitro. 8-Nitroguanine in acid-hydrolyzed DNA was chemically reduced into 8-aminoguanine, which was analyzed using high performance liquid chromatography with electrochemical detection. Only peroxynitrite, but not nitrite, tetranitromethane nor NO-releasing compounds, formed 8-nitroguanine. Antioxidants and desferrioxamine inhibited the reaction. 8-Nitroguanine was depurinated from DNA incubated at pH 7.4, 37 degrees C (t1/2 = approximately 4 h). Peroxynitrite did not increase 8-oxoguanine levels in DNA.

摘要

过氧亚硝酸盐是一氧化氮与超氧化物在炎症组织中反应形成的一种强氧化剂。我们已经证明,在体外与低浓度过氧亚硝酸盐孵育的小牛胸腺DNA中,8-硝基鸟嘌呤呈剂量依赖性形成。酸水解DNA中的8-硝基鸟嘌呤被化学还原为8-氨基鸟嘌呤,然后使用高效液相色谱-电化学检测法进行分析。只有过氧亚硝酸盐能形成8-硝基鸟嘌呤,而亚硝酸盐、四硝基甲烷或一氧化氮释放化合物则不能。抗氧化剂和去铁胺抑制了该反应。在pH 7.4、37℃孵育的DNA中,8-硝基鸟嘌呤发生脱嘌呤作用(半衰期约为4小时)。过氧亚硝酸盐不会增加DNA中8-氧代鸟嘌呤的水平。

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