Endogenous Formation of Novel Halogenated 2′-Deoxycytidine HYPOHALOUS ACID-MEDIATED DNA MODIFICATION AT THE SITE OF INFLAMMATION

摘要: A potential role of DNA damage by leukocyte-derived reactive species in carcinogenesis has been suggested. Leukocyte-derived peroxidases, such as myeloperoxidase and eosinophil peroxidase, use hydrogen peroxide halides (Cl- Br-) to generate hypohalous acids (HOCl HOBr), halogenating intermediates. It suggested that these oxidants lead the formation halogenated products upon reaction with nucleobases. To verify consequences phagocyte-mediated at site inflammation, we developed a novel monoclonal antibody (mAb2D3) recognizes acid-modified found most significantly recognized HOCl/HOBr-modified 2′-deoxycytidine residues. The immunoreactivity HOCl-treated oligonucleotide was attenuated excess methionine, suggesting chloramine-like may be plausible epitopes antibody. On basis further characterization combined mass spectrometric analysis, mAb2D3 were determined N4,5-dihalogenated dihalogenated vivo immunohistochemically demonstrated lung liver nuclei mice treated lipopolysaccharides, an experimental inflammatory model. These results strongly suggest phagocyte-derived oxidants, acids, endogenously bases vivo. Halogenation (chlorination and/or bromination) therefore constitute one mechanism for oxidative inflammation.