Sources of extracellular, oxidatively-modified DNA lesions: Implications for their measurement in urine

Marcus S. Cooke, Paul Henderson, Mark D. Evans

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

There is a robust mechanistic basis for the role of oxidation damage to DNA in the aetiology of various major diseases (cardiovascular, neurodegenerative, cancer). Robust, validated biomarkers are needed to measure oxidative damage in the context of molecular epidemiology, to clarify risks associated with oxidative stress, to improve our understanding of its role in health and disease and to test intervention strategies to ameliorate it. Of the urinary biomarkers for DNA oxidation, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) is the most studied. However, there are a number of factors which hamper our complete understanding of what meausrement of this lesion in urine actually represents. DNA repair is thought to be a major contributor to urinary 8-oxodG levels, although the precise pathway(s) has not been proven, plus possible contribution from cell turnover and diet are possible confounders. Most recently, evidence has arisen which suggests that nucleotide salvage of 8-oxodG and 8-oxoGua can contribute substantially to 8-oxoG levels in DNA and RNA, at least in rapidly dividing cells. This new observation may add an further confounder to the conclusion that 8-oxoGua or 8-oxodG, and its nucleobase equivalent 8-oxoguanine, concentrations in urine are simply a consequence of DNA repair. Further studies are required to define the relative contributions of metabolism, disease and diet to oxidised nucleic acids and their metabolites in urine in order to develop urinalyis as a better tool for understanding human disease.

Original languageEnglish (US)
Pages (from-to)255-270
Number of pages16
JournalJournal of Clinical Biochemistry and Nutrition
Volume45
Issue number3
DOIs
StatePublished - Nov 2009

Keywords

  • Cell death
  • DNA damage
  • DNA repair
  • Oxidative stress
  • Urine

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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