Urinary 8-hydroxy-2'-deoxyguanosine as a biological marker of in vivo oxidative DNA damage

Proc Natl Acad Sci U S A. 1989 Dec;86(24):9697-701. doi: 10.1073/pnas.86.24.9697.

Abstract

DNA is subject to constant oxidative damage from endogenous oxidants. The oxidized DNA is continuously repaired and the oxidized bases are excreted in the urine. A simple routine analytical procedure is described for urinary 8-hydroxy-2'-deoxyguanosine, an oxidative DNA damage adduct, as an indicator of oxidative damage in humans and rodents. This adduct was purified from human urine and characterized. The described assay employs a series of solid-phase extraction steps that separate 8-hydroxy-2'-deoxyguanosine from other urinary constituents, followed by analysis by gradient reversed-phase HPLC coupled to a dual-electrode high-efficiency electrochemical detection system. Analysis of urine from three species by this method indicates that mice excrete approximately 3.3-fold more 8-hydroxy-2'-deoxyguanosine than humans (582 vs. 178 residues per cell per day), a result that supports the proposal that oxidative damage to DNA increases in proportion to species-specific basal metabolic rates.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Biomarkers / urine*
  • Chromatography, High Pressure Liquid
  • DNA Damage*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / chemical synthesis
  • Deoxyguanosine / isolation & purification
  • Deoxyguanosine / urine
  • Humans
  • Mice
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred F344
  • Reference Values
  • Species Specificity

Substances

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