Oxidative DNA damage following photoexcitation of daunomycin: Direct role of oxygen

The chemistry of the photoactivation of daunomycin-DNA complexes is reported and the mechanism is elucidated. We quantitatively assessed the type of DNA damage, such as strand breaks, oxidized bases, and abasic sites, that arise using a plasmid relaxation assay coupled with DNA repair endonucleases. Photoexcitation of daunomycin leads to oxidative DNA damage in a dose- and irradiation time-dependent manner and guanine-specific oxidized purines are substantially produced under these conditions. Oxidative DNA base damage was also inhibited by argon degassing, indicating that guanine-specific damage arises from an oxygen-dependent mechanism. In addition, photoexcitation of daunomycin-DNA complexes leads to superoxide anion radical formation. From these studies of the actual product formed, we conclude that a charge transfer is a main driving force of the mechanism.