Yermilov V, Rubio J, Becchi M, Friesen M D, Pignatelli B, Ohshima H
International Agency for Research on Cancer, Lyon, France.
Carcinogenesis. 1995 Sep;16(9):2045-50. doi: 10.1093/carcin/16.9.2045.
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 approximately 80% of all compounds formed) as 8-nitroguanine. Its formation was maximal at approximately 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.
一氧化氮和超氧阴离子均在炎症组织中生成，它们迅速反应形成过氧亚硝酸根阴离子（ONOO-），这是一种强氧化剂，可引发具有羟基自由基（HO·）、硝鎓离子（NO2+）和二氧化氮自由基（NO2·）特征的反应。因此，过氧亚硝酸根可能会导致DNA或组织损伤，从而促进多阶段致癌过程。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根的反应。在生理条件下，鸟嘌呤与过氧亚硝酸根迅速反应并形成几种物质，其中两种呈黄色，这是硝基和亚硝基化合物的特征。基于色谱和光谱证据，我们将主要化合物（约占所有生成化合物的80%）鉴定为8-硝基鸟嘌呤。其形成在pH约为8时达到最大值，并随过氧亚硝酸根浓度呈剂量依赖性增加，但不依赖于鸟嘌呤浓度。已证明能催化酪氨酸硝化的铁离子的存在并不影响鸟嘌呤的硝化。8-硝基鸟嘌呤可作为炎症组织中过氧亚硝酸根诱导的DNA损伤的特异性标志物。
