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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

Published

Author(s)

Pawel Jaruga, M Miral Dizdar

Abstract

Oxidatively induced DNA damage occurs in living organisms by endogenous and exogenous sources, and is implicated in a variety of disease processes including carcinogenesis and aging. Therefore, biomarkers of oxidatively induced DNA damage are of great interest. Products of DNA damage can potentially be used as biomarkers 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. For this purpose, we applied a recently developed methodology using LC/MS/MS with isotope-dilution. Urine samples were collected from volunteers in the Biochemical Science Division as the first sample in the morning before food intake. The samples were purified using a commercially available purification system and then analyzed by LC/MS/MS. R-cdA and S-cdA were detected in urine samples and quantified using their stable isotope-labeled analogues as internal standards. Creatinine levels were also measured. In addition, we measured a commonly used modified nucleoside, 8-hydroxy-2 -deoxyguanosine, 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 with isotope-dilution. We propose that R-cdA and S-cdA may be well-suited biomarkers for disease processes such as carcinogenesis.
Citation
Biochemical and Biophysical Research Communications
Volume
397
Issue
1

Keywords

Biomarkers, Carcinogenesis, DNA damage, LC/MS/MS, Nucleotide excision repair

Citation

Jaruga, P. and , M. (2010), 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, Biochemical and Biophysical Research Communications, [online], https://doi.org/10.1016/j.bbrc.2010.05.050 (Accessed October 3, 2022)
Created June 18, 2010, Updated November 10, 2018