Abstract

The effects of four anthracyclines, adriamycin, carminomycin, aclacinomycin, and marcellomycin, on covalently closed circular PM-2 DNA were studied. At a concentration of 5-10 µM each anthracycline induced conformational changes in PM-2 DNA demonstrated by production of diffuse staining patterns on agarose gels. No significant PM-2 DNA degradation was observed using alkaline sucrose gradient centrifugation, agarose gel electrophoresis analysis nor by a PM-2 DNA fluorescence assay using alkaline denaturation. At higher concentrations (200 µM) and in the presence of reducing agents and high temperature, the anthracyclines were able to degrade PM-2 DNA. Bleomycin A₂ was used to test whether the conformational changes induced by anthracyclines were due to random breakage, and Bleomycin A₂ was shown to degrade the anthracycline bound PM-2 DNA confirming that the anthracyclines did not degrade PM-2 DNA. Further, these results suggest that anthracyclines bind to PM-2 DNA, and induce significant conformational changes that do not affect Bleomycin A₂-induced DNA degradation.