Immunohistochemical detection of a substituted 1,N2-ethenodeoxyguanosine adduct by ω-6 polyunsaturated fatty acid hydroperoxides in the liver of rats fed a choline-deficient, L-amino acid-defined diet

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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,N2-etheno-2′-deoxyguanosine adduct (Oxo-heptyl-εdG), one of the major products from the reaction of 13-hydroperoxyoctadecadienoic acid (13-HPODE) with dG. The monoclonal antibody specific to Oxo-heptyl-εdG was prepared using a chemically synthesized conjugate of Oxo-heptyl-εdG and carrier protein as immunogen. The characterization showed that the obtained antibody (mAb6A3) is specific to the Oxo-heptyl-εdG moiety. Using the novel antibody, the presence of the Oxo-heptyl-εdG 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-εdG formation was confirmed in DNAs treated with peroxidized linoleic acid, arachidonic acid and γ-linolenic acid, respectively, suggesting that the hydroperoxides of ω-6 polyunsaturated fatty acids could be the potential sources of Oxo-heptyl-εdG formation in vivo. Collectively, the results in this study suggest the first evidence that the formation of Oxo-heptyl-εdG, the ω-6 lipid hydroperoxide-mediated DNA adduct, may be a potential biomarker for the early phase of carcinogenesis.

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