Impact of copper on the induction and repair of oxidative DNA damage, poly(ADP-ribosyl)ation and PARP-1 activity

Tanja Schwerdtle, Ingrit Hamann, Gunnar Jahnke, Ingo Walter, Constanze Richter, Jason L Parsons, Grigory L Dianov, Andrea Hartwig

Research output: Contribution to journalArticlepeer-review


Copper is an essential trace element involved, among other functions, in enzymatic antioxidative defense systems. However, nonprotein bound copper ions have been shown to generate reactive oxygen species. To gain insight into the discrepancy between the protective properties of copper on the one hand and its toxicity on the other hand, we examined the genotoxic effects of CuSO(4) in cultured human cells. Here we report that copper, at cytotoxic concentrations, induces oxidative DNA base modifications and DNA strand breaks. However, at lower noncytotoxic concentrations, copper inhibits the repair of oxidative DNA damage induced by visible light. As a first mechanistic hint, inhibition of H(2)O(2)-induced poly(ADP-ribosyl)ation was identified in cultured cells and further experiments demonstrated a strong inhibition of the activity of isolated poly(ADP-ribose)polymerase-1 (PARP-1) by copper. Bioavailability studies of copper showed a dose-dependent uptake in cells and pointed out the relevance of the applied concentrations. Taken together, the results indicate that copper, under conditions of either disturbed homeostasis or overload due to high exposure, exerts defined genotoxic effects. Hence, a balance needs to be maintained to ensure sufficient uptake and to prevent overload.

Original languageEnglish
Pages (from-to)201-10
Number of pages10
JournalMolecular Nutrition & Food Research
Issue number2
Publication statusPublished - Feb 2007


  • Copper/metabolism
  • DNA Breaks
  • DNA Damage/drug effects
  • DNA Repair/drug effects
  • HeLa Cells
  • Humans
  • Oxidation-Reduction
  • Poly (ADP-Ribose) Polymerase-1
  • Poly Adenosine Diphosphate Ribose/metabolism
  • Poly(ADP-ribose) Polymerases/metabolism


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