PHOTOSENSITIZED DEGRADATION OF DNA BY DAUNOMYCIN

Abstract

Abstract Visible irradiation of DNA‐daunomycin solutions resulted in a decrease of viscosity of the DNA and an increase of the rate of denaturation of DNA in formaldehyde. These changes are consistent with the induction of single‐strand breaks in the DNA, some of which pair to cause fragmentation of the DNA. The DNA damage increases with drug: nucleotide ratio up to 0.2 and is diminished beyond that range. The damage also increases with ionic strength up to 0.6 M and is diminished above that value. These results suggest that the non‐intercalated form of the drug is involved in the photosensitization process. Radicals that are produced accompanying the degradation have been trapped by 5,5‐dimeth‐yl‐l‐pyrroline‐1‐oxide and identified as hydroxyl radicals from their ESR spectrum. The DNA photosensitized damage is completely inhibited when hydroxyl radicals are removed by the spin‐trap, suggesting a direct role for the hydroxyl radicals in the DNA photosensitized degradation process. The implications of the photosensitized DNA damage and the production of hydroxyl radicals in this process are discussed with respect to the medical uses and chemotherapeutic role of daunomycin.