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Oxidatively generated modifications to nucleic acids in vivo: Measurement in urine and plasma

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  1. Urinary markers of nucleic acid oxidation increase with age, obesity and insulin resistance in Danish children and adolescents

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  2. Interventions targeted at oxidatively generated modifications of nucleic acids focused on urine and plasma markers

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  3. The Effect of Different Training Intensities on Oxidatively Generated Modifications of Nucleic Acids: A Randomized, Controlled Trial

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  4. RNA oxidation and iron levels in patients with diabetes

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BACKGROUND: The oxidized guanine nucleosides, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), derived from DNA and RNA, respectively, were used to investigate the importance of oxidative stress to nucleic acids in vivo. High urinary excretion of 8-oxodG is associated with cancer development, whereas high urinary excretion of 8-oxoGuo is associated with mortality in type 2 diabetes. Like creatinine, these small water-soluble molecules are not reabsorbed in the kidney. Therefore, 8-oxo nucleoside/creatinine reciprocal concentration ratios are identical in plasma and urine. The total amount of 8-oxo guanine nucleosides excreted by the kidneys is the product of plasma concentration and glomerular filtration rate.

METHODS: With relevant equations and an estimated glomerular filtration rate, the 24-h urinary excretion of 8-oxodG and 8-oxoGuo was calculated in 2679 subjects with type 2 diabetes, displaying good correlation with the measured urinary 8-oxo nucleoside/creatinine ratio: DNA oxidation r = 0.86 and RNA oxidation r = 0.84 (p < 0.05 for both).

RESULTS: Survival analyses based on the quartiles of the 8-oxodG/creatinine ratio and the quartiles of calculated 24-h urinary excretion rate of the 2679 subjects gave similar hazard ratio estimates for death due to all causes. This finding was similar for the 8-oxoGuo hazard ratio estimates.

CONCLUSIONS: This study shows that oxidatively generated modifications to DNA and RNA in vivo can be measured using 1) a spot urine sample, normalized to urinary creatinine, 2) 24-h urine, or 3) a single plasma sample based on concentrations of 8-oxo nucleoside and creatinine and glomerular filtration rate.

Original languageEnglish
JournalFree Radical Biology & Medicine
Pages (from-to)336-341
Number of pages6
Publication statusPublished - Dec 2019

    Research areas

  • Biomarker, Diabetes, Nucleic acid oxidation, Oxidative stress, Prognosis

ID: 58090331