Nickel(II)-catalysed oxidative guanine and DNA damage beyond 8-oxoguanine

Free Radic Biol Med. 2007 Jun 1;42(11):1680-9. doi: 10.1016/j.freeradbiomed.2007.02.025. Epub 2007 Feb 28.

Abstract

Oxidative DNA damage is one of the most important and most studied mechanisms of disease. It has been associated with a range of terminal diseases such as cancer, heart disease, hepatitis, and HIV, as well as with a variety of everyday ailments. There are various mechanisms by which this type of DNA damage can be initiated, through radiation and chemical oxidation, among others; however, these mechanisms have yet to be fully elucidated. A HPLC-UV-EC study of the oxidation of DNA mediated by nickel(II) obtained results that show an erratic, almost oscillatory formation of 8-oxoguanine (8-oxoG) from free guanine and from guanine in DNA. Sporadic 8-oxoG concentrations were also observed when 8-oxoG alone was subjected to these conditions. A HPLC-MS/MS study showed the formation of oxidised-guanidinohydantoin (oxGH) from free guanine at pH 11, and the formation of guanidinohydantoin (GH) from DNA at pH 5.5.

MeSH terms

  • Catalysis
  • Chromatography, High Pressure Liquid
  • DNA / chemistry
  • DNA / drug effects*
  • DNA Damage*
  • Guanine / analogs & derivatives*
  • Guanine / analysis
  • Guanine / chemistry*
  • Mass Spectrometry
  • Nickel / toxicity*
  • Oxidation-Reduction

Substances

  • 8-hydroxyguanine
  • Guanine
  • Nickel
  • DNA