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
Pub Type: Journals
atherosclerosis, biomarkers, 8, 5'-cyclo-2'-deoxyadenosines, DNA damage, oxidative stress