Oxidative DNA damage induced by nitrotyrosine, a biomarker of inflammation.
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.
Department of Environmental and Molecular Medicine, Mie University School of Medicine, Edobashi, Tsu, Mie 514-8507, Japan.
Mariko
M
Murata
Shosuke
S
Kawanishi
D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers; D003300:Copper / Q000633:toxicity; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D018384:Oxidative Stress; D010618:Phenanthrolines / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*
D015415:Biomarkers; D016166:Free Radical Scavengers; D010618:Phenanthrolines; C002744:3-nitrotyrosine; D014443:Tyrosine; D009249:NADP; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C427203:calf thymus DNA; C002478:bathocuproine; D009251:NADPH-Ferrihemoprotein Reductase; D003849:Deoxyguanosine