Journal Article

Immunohistochemical detection of a substituted 1,<i>N</i><sup>2</sup>-ethenodeoxyguanosine adduct by ω-6 polyunsaturated fatty acid hydroperoxides in the liver of rats fed a choline-deficient, L-amino acid-defined diet

Yoshichika Kawai, Yoji Kato, Dai Nakae, Osamu Kusuoka, Yoichi Konishi, Koji Uchida and Toshihiko Osawa

in Carcinogenesis

Volume 23, issue 3, pages 485-489
Published in print March 2002 | ISSN: 0143-3334
Published online March 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.3.485
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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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.

Keywords: ACR, acrolein;; BSA, bovine serum albumin;; CDAA, choline-deficient, l-amino acid-defined;; CSAA, choline-supplemented, l-amino acid-defined;; dG, 2′-deoxyguanosine;; ELISA, enzyme-linked immunosorbent assay;; Gua, guanosine;; HNE, 4-hydroxy-2-nonenal;; 13-HPODE, 13-hydroperoxyoctadecadienac acid;; KLH, keyhole limpet hemocyanin;; MDA, malondialdehyde;; ONE, 4-oxo-2-nonenal;; PBS, phosphate-buffered saline;; TBARS, thiobarbituric acid-reactive substances;; TPBS, PBS containing 0.05% Tween-20.

Journal Article.  3694 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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