Spencer J P, Wong J, Jenner A, Aruoma O I, Cross C E, Halliwell B
Neurodegenerative Disease Research Centre, University of London King's College, U.K.
Chem Res Toxicol. 1996 Oct-Nov;9(7):1152-8. doi: 10.1021/tx960084i.
Exposure of isolated calf thymus DNA and human skin epidermal keratinocytes to peroxynitrite or the peroxynitrite generator, 3-morpholinosydnonimine (SIN-1), led to extensive DNA base modification. Large increases in xanthine and hypoxanthine, possible deamination products of guanine and adenine, respectively, and in 8-nitroguanine were observed, but only small changes in some oxidized base products were seen. This pattern of damage suggests that hydroxyl radicals were not major contributors to base modification caused by peroxynitrite, as OH is known to cause multiple oxidative modifications to all four DNA bases. Instead, it seems that reactive nitrogen species play a much greater role in the mechanism of base damage, producing both nitration and deamination of purine bases when DNA or whole cells are exposed to peroxynitrite. If this pattern of damage is unique to peroxynitrite, it might act as a marker of cellular damage by this species in vivo.
将分离的小牛胸腺DNA和人皮肤表皮角质形成细胞暴露于过氧亚硝酸盐或过氧亚硝酸盐生成剂3-吗啉代-sydnonimine（SIN-1）中，会导致广泛的DNA碱基修饰。观察到黄嘌呤和次黄嘌呤大幅增加，它们分别可能是鸟嘌呤和腺嘌呤的脱氨产物，8-硝基鸟嘌呤也增加，但某些氧化碱基产物仅有微小变化。这种损伤模式表明，羟基自由基并非过氧亚硝酸盐引起碱基修饰的主要因素，因为已知羟基会对所有四种DNA碱基造成多种氧化修饰。相反，活性氮物种似乎在碱基损伤机制中起更大作用，当DNA或整个细胞暴露于过氧亚硝酸盐时，会导致嘌呤碱基的硝化和脱氨。如果这种损伤模式是过氧亚硝酸盐所特有的，那么它可能作为该物质在体内造成细胞损伤的标志物。
