Bromination of deoxycytidine by eosinophil peroxidase: A mechanism for mutagenesis by oxidative damage of nucleotide precursors
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- Jeffrey P. Henderson
- Departments of Medicine, Pediatrics, Radiology, and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Research Service, Veterans Administration Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52241
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- Jaeman Byun
- Departments of Medicine, Pediatrics, Radiology, and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Research Service, Veterans Administration Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52241
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- Michelle V. Williams
- Departments of Medicine, Pediatrics, Radiology, and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Research Service, Veterans Administration Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52241
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- Michael L. McCormick
- Departments of Medicine, Pediatrics, Radiology, and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Research Service, Veterans Administration Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52241
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- William C. Parks
- Departments of Medicine, Pediatrics, Radiology, and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Research Service, Veterans Administration Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52241
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- Lisa A. Ridnour
- Departments of Medicine, Pediatrics, Radiology, and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Research Service, Veterans Administration Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52241
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- Jay W. Heinecke
- Departments of Medicine, Pediatrics, Radiology, and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110; and Research Service, Veterans Administration Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52241
書誌事項
- 公開日
- 2001-02-06
- DOI
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- 10.1073/pnas.98.4.1631
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p>Oxidants generated by eosinophils during chronic inflammation may lead to mutagenesis in adjacent epithelial cells. Eosinophil peroxidase, a heme enzyme released by eosinophils, generates hypobromous acid that damages tissue in inflammatory conditions. We show that human eosinophils use eosinophil peroxidase to produce 5-bromodeoxycytidine. Flow cytometric, immunohistochemical, and mass spectrometric analyses all demonstrated that 5-bromodeoxycytidine generated by eosinophil peroxidase was taken up by cultured cells and incorporated into genomic DNA as 5-bromodeoxyuridine. Although previous studies have focused on oxidation of chromosomal DNA, our observations suggest another mechanism for oxidative damage of DNA. In this scenario, peroxidase-catalyzed halogenation of nucleotide precursors yields products that subsequently can be incorporated into DNA. Because the thymine analog 5-BrUra mispairs with guanine in DNA, generation of brominated pyrimidines by eosinophils might constitute a mechanism for cytotoxicity and mutagenesis at sites of inflammation.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 98 (4), 1631-1636, 2001-02-06
Proceedings of the National Academy of Sciences