Oxidative DNA damage induced by nitrotyrosine, a biomarker of inflammation |
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Authors: | Murata Mariko Kawanishi Shosuke |
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Affiliation: | Department of Environmental and Molecular Medicine, Mie University School of Medicine, Edobashi, Tsu, Mie 514-8507, Japan. |
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Abstract: | Inflammation has been postulated as a risk factor for several cancers. 3-Nitrotyrosine is a biochemical marker for inflammation. We investigated the ability of nitrotyrosine and nitrotyrosine-containing peptides (nitroY-peptide) to induce DNA damage by the experiments using 32P-labeled DNA fragments obtained from the human p53 tumor suppressor gene and an HPLC-electrochemical detector. Nitrotyrosine and nitroY-peptide caused Cu(II)-dependent DNA damage in the presence of P450 reductase, which is considered to yield nitroreduction. Catalase inhibited DNA damage, suggesting the involvement of H2O2. Nitrotyrosine and nitroY-peptide increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, an indicator of oxidative DNA damage. Nitrotyrosine-containing peptides of histone induced 8-oxodG formation more efficiently than free nitrotyrosine. We propose the possibility that nitrotyrosine-induced H2O2 formation and DNA damage contribute to inflammation-associated carcinogenesis. |
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Keywords: | Nitrotyrosine Oxidative DNA damage P450 reductase Copper Hydrogen peroxide Inflammation Carcinogenesis |
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