Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, DK-2200 Copenhagen, Denmark.
Free Radic Biol Med. 2009 Oct 15;47(8):1230-3. doi: 10.1016/j.freeradbiomed.2009.08.004. Epub 2009 Aug 14.
Oxidatively generated damage to nucleic acids is considered to play a significant role in carcinogenesis, and it has been shown that people with hereditary hemochromatosis are at increased risk of cancer. In this study we used a new refined liquid chromatography-tandem mass spectrometry method to measure the urinary excretion of oxidatively generated 8-oxo-7,8-dihydroguanine and related 2'-deoxyribonucleoside and ribonucleoside derivatives in hereditary hemochromatosis patients, and we investigated the effect of treatment on the levels of these modifications. The study was carried out as a classical case-control study of 21 newly diagnosed, never treated hereditary hemochromatosis patients and 21 matched controls. We found that at baseline the urinary excretion of the RNA oxidation product 8-oxo-7,8-dihydroguanosine (8-oxoGuo) was 2.5-fold increased in patients compared with controls, and after phlebotomy treatment the excretion of the RNA oxidation product 8-oxoGuo returned to control values and the excretion of the DNA product 8-oxo-7,8-dihydro-2'-deoxyguanosine was reduced by 30%. In patients with hereditary hemochromatosis oxidative stress on nucleic acids is an important feature of the iron overload seen in this disease. By this mechanism cellular damage resulting in end organ damage, typically seen in the liver of such patients, may be mediated.
氧化生成的核酸损伤被认为在致癌作用中起重要作用，并且已经表明遗传性血色素沉着症患者癌症风险增加。在这项研究中，我们使用一种新的改良液相色谱-串联质谱法来测量遗传性血色素沉着症患者尿液中氧化生成的 8-氧代-7,8-二氢鸟嘌呤和相关 2'-脱氧核苷和核糖核苷衍生物的排泄情况，并研究了治疗对这些修饰物水平的影响。该研究是对 21 名新诊断、未经治疗的遗传性血色素沉着症患者和 21 名匹配对照进行的经典病例对照研究。我们发现，在基线时，与对照组相比，患者的 RNA 氧化产物 8-氧代-7,8-二氢鸟苷（8-氧代鸟苷）的尿排泄增加了 2.5 倍，并且在放血治疗后，RNA 氧化产物 8-氧代鸟苷的排泄恢复到对照值，DNA 产物 8-氧代-7,8-二脱氧鸟苷的排泄减少了 30%。在遗传性血色素沉着症患者中，核酸的氧化应激是这种疾病中观察到的铁过载的一个重要特征。通过这种机制，可能介导导致终末器官损伤的细胞损伤，通常在这些患者的肝脏中可见。
