Identification and quantification of (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines in human urine as putative biomarkers of oxidatively induced damage to DNA.
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.
Jaruga
Pawel
P
Biochemical Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA. pawel.jaruga@nist.gov
Dizdaroglu
Miral
M
D015415:Biomarkers / Q000652:urine; D002471:Cell Transformation, Neoplastic; D002853:Chromatography, Liquid; D003404:Creatinine / Q000652:urine; D004249:DNA Damage; D003839:Deoxyadenosines / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D018384:Oxidative Stress
D015415:Biomarkers; D003839:Deoxyadenosines; C056752:8,5'-cyclo-2'-deoxyadenosine; D003404:Creatinine