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

Free Radic Biol Med. 2019 Dec;145:336-341. doi: 10.1016/j.freeradbiomed.2019.10.001. Epub 2019 Oct 3.

Abstract

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.

Keywords: Biomarker; Diabetes; Nucleic acid oxidation; Oxidative stress; Prognosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine / blood
  • 8-Hydroxy-2'-Deoxyguanosine / urine
  • Biomarkers* / blood
  • Biomarkers* / urine
  • DNA Damage
  • Humans
  • Neoplasms* / blood
  • Neoplasms* / urine
  • Nucleic Acids / blood
  • Nucleic Acids / chemistry
  • Nucleic Acids / urine
  • Oxidative Stress / genetics
  • Proportional Hazards Models

Substances

  • Biomarkers
  • Nucleic Acids
  • 8-Hydroxy-2'-Deoxyguanosine