FORMATION OF 8-NITROGUANINE BY THE REACTION OF GUANINE WITH PEROXYNITRITE IN-VITRO
FORMATION OF 8-NITROGUANINE BY THE REACTION OF GUANINE WITH PEROXYNITRITE IN-VITRO
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DOI：
10.1093/carcin/16.9.2045
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发表时间：
1995-09-01
期刊：
影响因子：
4.7
通讯作者：
OHSHIMA, H
中科院分区：
文献类型：
--
作者：
YERMILOV, V;RUBIO, J;OHSHIMA, H
炎症组织中形成的一氧化氮和超氧阴离子迅速反应生成过氧亚硝酸盐阴离子（ONOO-），这是一种强氧化剂，能引发以羟基自由基（HO.）、氮离子（NO2+）和二氧化氮自由基（NO2）为特征的反应。因此，过氧亚硝酸盐可能导致DNA或组织损伤，导致多阶段癌变过程。我们在体外研究了各种碱基、核苷或脱氧核苷与过氧亚硝酸盐的反应。鸟嘌呤在生理条件下与过氧亚硝酸盐迅速反应，生成多种物质，其中两种物质呈黄色，这是硝基和亚硝基化合物的特征。根据色谱和光谱证据，我们确定了主要化合物（约占所有化合物的80%）为8-硝基鸟嘌呤。它的形成在pH值接近于8时达到最大值，并随过氧亚硝酸盐浓度的增加而增加，但与鸟嘌呤浓度无关。铁离子的存在，已被证明可以催化酪氨酸的硝化作用，但不影响鸟嘌呤的硝化作用。8-硝基鸟嘌呤可作为过氧亚硝酸盐诱导的炎症组织DNA损伤的特异性标记物。
Nitric oxide and superoxide anion, both formed in inflamed tissues, react rapidly to form the peroxynitrite anion (ONOO-), a strong oxidant which can initiate reactions characteristic of hydroxyl radical (HO.), nitronium ion (NO2+) and nitrogen dioxide radical (NO2.). Peroxynitrite, therefore, may cause DNA or tissue damage, contributing to the multistage carcinogenesis process. We have studied reactions of various bases, nucleosides or deoxynucleosides with peroxynitrite in vitro. Guanine reacted rapidly with peroxynitrite under physiological conditions and formed several substances, two of which were yellow, a characteristic of nitro and nitroso compounds. On the basis of chromatographic and spectral evidence we identified the major compound (which accounts for similar to 80% of all compounds formed) as 8-nitroguanine. Its formation was maximal at similar to pH 8 and increased dose-dependently with peroxynitrite concentration, but was not dependent on guanine concentration. The presence of ferric ions, which has been shown to catalyse nitration of tyrosine, did not affect nitration of guanine. 8-Nitroguanine could act as a specific marker for DNA damage induced by peroxynitrite in inflamed tissues.