Biochemical Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
Biochem Biophys Res Commun. 2010 Jun 18;397(1):48-52. doi: 10.1016/j.bbrc.2010.05.050. Epub 2010 May 13.
Biomarkers of oxidatively induced DNA damage are of great interest and can potentially be used for the early detection of disease, monitoring the progression of disease and determining the efficacy of therapy. The present work deals with the measurement in human urine of (5'R)-8,5'-cyclo-2'-deoxyadenosine (R-cdA) and (5'S)-8,5'-cyclo-2'-deoxyadenosine (S-cdA). These modified nucleosides had hitherto not been considered or investigated to be present in urine as possible biomarkers of oxidatively induced DNA damage. Urine samples were collected from volunteers, purified and analyzed by LC-MS/MS with isotope-dilution. R-cdA and S-cdA were detected in urine and quantified. Creatinine levels were also measured. In addition, we measured 8-hydroxy-2'-deoxyguanosine that is commonly used as a biomarker. This study shows, for the first time, that R-cdA and S-cdA exist in human urine and can be identified and quantified by LC-MS/MS. We propose that R-cdA and S-cdA may be well-suited biomarkers for disease processes such as carcinogenesis.
氧化诱导的 DNA 损伤的生物标志物具有重要的研究意义，并且可能被用于疾病的早期检测、疾病进展的监测以及治疗效果的评估。本研究致力于测量人尿液中的（5'R）-8,5'-环-2'-脱氧腺苷（R-cdA）和（5'S）-8,5'-环-2'-脱氧腺苷（S-cdA）。这些修饰核苷此前并未被认为或研究过是否存在于尿液中，作为氧化诱导的 DNA 损伤的潜在生物标志物。志愿者的尿液样本被收集、纯化并通过 LC-MS/MS 进行分析，采用同位素稀释法进行定量。R-cdA 和 S-cdA 在尿液中被检测到并被定量。肌酐水平也进行了测量。此外，我们还测量了通常被用作生物标志物的 8-羟基-2'-脱氧鸟苷。本研究首次表明，R-cdA 和 S-cdA 存在于人类尿液中，并且可以通过 LC-MS/MS 进行鉴定和定量。我们提出，R-cdA 和 S-cdA 可能是适合用于癌症发生等疾病过程的生物标志物。
