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

EPR spectroscopy provides direct evidence for the intercalation of copper(I I) complexes of 1,10-phenanthroline and 2,2'-bipyridine with DNA. Reduction of these complexes to copper(I) by glutathione is evidently facile, wherea s ascorbate reacts more slowly. Reoxidation of copper(I) with (BuOOH)-Bu-t (to give (BuO.)-Bu-t) is rapid in both systems, as judged by EPR spin-trapp ing results. Reaction of copper(I)-DNA with H2O2 in the presence of ascorba te leads to the generation of HO. and to the trapping of DNA-derived radica l adducts. The role of 1,10-phenanthroline and ascorbate, especially, and t he relevance to DNA scission, are discussed.