Substantial decrease of urinary 8-oxo-7,8-dihydroguanine, a product of the base excision repair pathway, in DNA glycosylase defective mice

Int J Biochem Cell Biol. 2005 Jun;37(6):1331-6. doi: 10.1016/j.biocel.2005.01.001.


Genome integrity is maintained via removal (repair) of DNA lesions and an increased load of such DNA damage has been linked to numerous pathological conditions, including carcinogenesis and ageing. 8-Oxo-7,8-dihydroguanine is one of the most critical lesions of this type. The free 8-oxo-7,8-dihydroguanine produced by the action of a specific DNA glycosylase is a potential source of this compound in urine. To date, there has been no direct, experimental evidence demonstrating that urinary 8-oxo-7,8-dihydroguanine is produced by the base excision repair pathway. For clarification of this issue, we applied a recently developed methodology which involved high performance liquid chromatography pre-purification followed by gas chromatography with isotope dilution mass spectrometric detection to compare the urinary excretion rate of 8-oxo-7,8-dihydroguanine in wild type and OGG1 glycosylase knock out mice. Our study revealed a 26% reduction in urinary level of 8-oxo-7,8-dihydroguanine in OGG1 deficient mice in comparison with the wild type strain. This clearly indicates that the mouse OGG1 glycosylase contributes significantly to the generation of urinary 8-oxo-7,8-dihydroguanine. Therefore, urinary measurements of 8-oxo-7,8-dihydroguanine may be attributed to DNA damage and repair, which in turn suggests that they may be useful in studying associations between DNA repair and disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • DNA Damage / physiology
  • DNA Glycosylases / deficiency
  • DNA Glycosylases / physiology*
  • DNA Repair*
  • Gas Chromatography-Mass Spectrometry
  • Guanine / analogs & derivatives*
  • Guanine / urine
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout


  • 8-hydroxyguanine
  • Guanine
  • DNA Glycosylases
  • Ogg1 protein, mouse