Immunochemical detection of glyoxal DNA damage

Free Radic Biol Med. 1999 May;26(9-10):1267-73. doi: 10.1016/s0891-5849(98)00326-8.

Abstract

The relevance of reactive oxygen species (ROS) in the pathogenesis of inflammatory diseases is widely documented. Immunochemical detection of ROS DNA adducts has been developed, however, recognition of glyoxal-DNA adducts has not previously been described. We have generated a polyclonal antibody that has shown increased antibody binding to ROS-modified DNA in comparison to native DNA. In addition, dose-dependent antibody binding to DNA modified with ascorbate alone was shown, with significant inhibition by desferrioxamine, catalase, and ethanol. Minimal inhibition was observed with uric acid, 1,10-phenanthroline and DMSO. However, antibody binding in the presence of EDTA increased 3500-fold. The involvement of hydrogen peroxide and hydroxyl radical in ascorbate-mediated DNA damage is consistent with ascorbate acting as a reducing agent for DNA-bound metal ions. Glyoxal is known to be formed during oxidation of ascorbate. Glyoxylated DNA, that previously had been proposed as a marker of oxidative damage, was recognised in a dose dependent manner using the antibody. We describe the potential use of our anti-ROS DNA antibody, that detects predominantly Fenton-type mediated damage to DNA and report on its specificity for the recognition of glyoxal-DNA adducts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear
  • Ascorbic Acid / toxicity
  • Cattle
  • DNA / chemistry
  • DNA / drug effects
  • DNA / immunology
  • DNA Adducts / analysis*
  • DNA Adducts / immunology
  • DNA Damage*
  • Enzyme-Linked Immunosorbent Assay
  • Glyoxal / analogs & derivatives*
  • Glyoxal / analysis
  • Hydrogen Peroxide / toxicity
  • Immunochemistry
  • In Vitro Techniques
  • Oxidation-Reduction
  • Rabbits
  • Reactive Oxygen Species

Substances

  • Antibodies, Antinuclear
  • DNA Adducts
  • Reactive Oxygen Species
  • Glyoxal
  • DNA
  • Hydrogen Peroxide
  • Ascorbic Acid