Immunohistochemical detection of a substituted 1,N(2)-ethenodeoxyguanosine adduct by omega-6 polyunsaturated fatty acid hydroperoxides in the liver of rats fed a choline-deficient, L-amino acid-defined diet

Carcinogenesis. 2002 Mar;23(3):485-9. doi: 10.1093/carcin/23.3.485.

Abstract

Endogenous lipid peroxidation products react with DNA and form exocyclic DNA adducts. The purpose of this study was to investigate the in vivo formation of 7-(2-oxo-heptyl)-substituted 1,N(2)-etheno-2'-deoxyguanosine adduct (Oxo-heptyl-varepsilondG), one of the major products from the reaction of 13-hydroperoxyoctadecadienoic acid (13-HPODE) with dG. The monoclonal antibody specific to Oxo-heptyl-varepsilondG was prepared using a chemically synthesized conjugate of Oxo-heptyl-varepsilondG and carrier protein as immunogen. The characterization showed that the obtained antibody (mAb6A3) is specific to the Oxo-heptyl-varepsilondG moiety. Using the novel antibody, the presence of the Oxo-heptyl-varepsilondG adduct in vivo was immunohistochemically revealed in the liver of rats fed a choline-deficient, L-amino acid-defined diet, an endogenous carcinogenesis model, for 3 days. In addition, the Oxo-heptyl-varepsilondG formation was confirmed in DNAs treated with peroxidized linoleic acid, arachidonic acid and gamma-linolenic acid, respectively, suggesting that the hydroperoxides of omega-6 polyunsaturated fatty acids could be the potential sources of Oxo-heptyl-varepsilondG formation in vivo. Collectively, the results in this study suggest the first evidence that the formation of Oxo-heptyl-varepsilondG, the omega-6 lipid hydroperoxide-mediated DNA adduct, may be a potential biomarker for the early phase of carcinogenesis.

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibody Specificity
  • Biomarkers / analysis
  • Choline / metabolism*
  • DNA Adducts / analysis
  • DNA Adducts / chemistry
  • DNA Adducts / immunology
  • DNA Adducts / metabolism*
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / analysis
  • Deoxyguanosine / immunology
  • Deoxyguanosine / metabolism*
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated / metabolism*
  • Food, Formulated
  • Immunohistochemistry
  • Lipid Peroxidation
  • Lipid Peroxides / metabolism*
  • Liver / metabolism*
  • Rats

Substances

  • Amino Acids
  • Antibodies, Monoclonal
  • Biomarkers
  • DNA Adducts
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Lipid Peroxides
  • Deoxyguanosine
  • Choline