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.

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.

• Authors: Yoshichika Kawai, Yoji Kato, Dai Nakae, Osamu Kusuoka, Yoichi Konishi, Koji Uchida, Toshihiko Osawa
• Journal: Carcinogenesis (Carcinogenesis) Vol. 23 Issue 3 Pg. 485-9 (Mar 2002) ISSN: 0143-3334 [Print] England
• PMID: 11895864 (Publication Type: Journal Article)

Chemical References

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

Topics

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