DNA damage via intercalation of copper complexes and activation by ascorbate and peroxides: direct EPR evidence for hydroxyl radical formation and reaction

Abstract

EPR spectroscopy provides direct evidence for the intercalation of copper(II) complexes of 1,10-phenanthroline and 2,2′-bipyridine with DNA. Reduction of these complexes to copper(I) by glutathione is evidently facile, whereas ascorbate reacts more slowly. Reoxidation of copper(I) with tBuOOH (to give tBuO˙) is rapid in both systems, as judged by EPR spin-trapping results. Reaction of copper(I)–DNA with H2O2 in the presence of ascorbate leads to the generation of HO˙ and to the trapping of DNA-derived radical adducts. The role of 1,10-phenanthroline and ascorbate, especially, and the relevance to DNA scission, are discussed.