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dc.contributor.authorBarbouti, A.en
dc.contributor.authorDoulias, P. T.en
dc.contributor.authorZhu, B. Z.en
dc.contributor.authorFrei, B.en
dc.contributor.authorGalaris, D.en
dc.rightsDefault Licence-
dc.subjectChelating Agents/pharmacologyen
dc.subjectCytosol/drug effectsen
dc.subjectDNA Damage/*drug effectsen
dc.subjectDNA, Single-Stranded/drug effectsen
dc.subjectDose-Response Relationship, Drugen
dc.subjectEgtazic Acid/*analogs & derivatives/pharmacologyen
dc.subjectGlucose Oxidase/pharmacologyen
dc.subjectHydrogen Peroxide/*toxicityen
dc.subjectIron Chelating Agents/pharmacologyen
dc.subjectJurkat Cells/drug effects/metabolismen
dc.subjectPentetic Acid/pharmacologyen
dc.subjectTime Factorsen
dc.titleIntracellular iron, but not copper, plays a critical role in hydrogen peroxide-induced DNA damageen
heal.type.enJournal articleen
heal.type.elΆρθρο Περιοδικούel
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.abstractThe role of intracellular iron, copper, and calcium in hydrogen peroxide-induced DNA damage was investigated using cultured Jurkat cells. The cells were exposed to low rates of continuously generated hydrogen peroxide by the glucose/glucose oxidase system, and the formation of single strand breaks in cellular DNA was evaluated by the sensitive method, single cell gel electrophoresis or "comet" assay. Pre-incubation with the specific ferric ion chelator desferrioxamine (0.1-5.0 mM) inhibited DNA damage in a time- and dose-dependent manner. On the other hand, diethylenetriaminepentaacetic acid (DTPA), a membrane impermeable iron chelator, was ineffective. The lipophilic ferrous ion chelator 1,10-phenanthroline also protected against DNA damage, while its nonchelating isomer 1,7-phenanthroline provided no protection. None of the above iron chelators produced DNA damage by themselves. In contrast, the specific cuprous ion chelator neocuproine (2,9-dimethyl-1,10-phenanthroline), as well as other copper-chelating agents, did not protect against H(2)O(2)-induced cellular DNA damage. In fact, membrane permeable copper-chelating agents induced DNA damage in the absence of H(2)O(2). These results indicate that, under normal conditions, intracellular redox-active iron, but not copper, participates in H(2)O(2)-induced single strand break formation in cellular DNA. Since BAPTA/AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester), an intracellular Ca(2+)-chelator, also protected against H(2)O(2)-induced DNA damage, it is likely that intracellular Ca(2+) changes are involved in this process as well. The exact role of Ca(2+) and its relation to intracellular transition metal ions, in particular iron, needs to be further investigated.en
heal.journalNameFree Radic Biol Meden
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