Intracellular iron, but not copper, plays a critical role in hydrogen peroxide-induced DNA damage (Journal article)

Barbouti, A./ Doulias, P. T./ Zhu, B. Z./ Frei, B./ Galaris, D.

The 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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Calcium/metabolism,Chelating Agents/pharmacology,Copper/*metabolism,Cytosol/drug effects,DNA Damage/*drug effects,DNA, Single-Stranded/drug effects,Dose-Response Relationship, Drug,Egtazic Acid/*analogs & derivatives/pharmacology,Ethylenediamines/pharmacology,Glucose Oxidase/pharmacology,Humans,Hydrogen Peroxide/*toxicity,Iron/*metabolism,Iron Chelating Agents/pharmacology,Jurkat Cells/drug effects/metabolism,Oxidation-Reduction,Pentetic Acid/pharmacology,Phenanthrolines/pharmacology,Time Factors
ISSN: 0891-5849
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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