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Publication Citation: DNA damage products (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines as potential biomarkers for atherosclerosis in human urine

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Author(s): M Miral Dizdar; Pawel Jaruga; R Olinski; Rafal Rozalski;
Title: DNA damage products (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines as potential biomarkers for atherosclerosis in human urine
Published: February 23, 2012
Abstract: Rationale: We hypothesized that oxidatively induced DNA damage products (5'R)-8,5'-cyclo-2'-deoxyadenosine (R-cdA) and (5'S)-8,5'-cyclo-2'-deoxyadenosine (S-cdA) may be well-suited as biomarkers for atherosclerosis in human urine. Objective: We tested this hypothesis by accurately measuring the levels of R-cdA and S-cdA in urines of atherosclerosis and healthy individuals. Methods and Results: We collected urine samples from 22 patients with clinical atherosclerosis and from 22 healthy individuals. The levels of R-cdA and S-cdA, and another typical product of DNA damage 8-hydroxy-2'-deoxyguanosine (8-OH-dG) were simultaneously measured using liquid chromatography-tandem mass spectrometry with isotope dilution. We show the presence of R-cdA and S-cdA at significantly greater concentrations in urine of atherosclerosis patients than in that of healthy individuals with a p-value < 0.0001. The p-value equaled to 0.0008 for the higher concentration of 8-OH-dG in patients than in controls. The concentrtations of R-cdA and S-cdA were at least two-orders of magnitude less than that of 8-OH-dG. Conclusions: Our data suggest that R-cdA and S-cdA can be sensitively and accurately measured in human urine as potential biomarkers of atherosclerosis using a non-invasive procedure for early detection, monitoring and outcome of therapy, testing of drugs and epidemiological studies.
Citation: ACS Biochemistry
Issue: 51
Pages: pp. 1822 - 1824
Keywords: atherosclerosis, biomarkers, 8,5'-cyclo-2'-deoxyadenosines, DNA damage, oxidative stress
Research Areas: DNA
DOI: http://dx.doi.org/10.1021/bi201912c  (Note: May link to a non-U.S. Government webpage)
PDF version: PDF Document Click here to retrieve PDF version of paper (492KB)