Abstract
The DNA-damaging activities of doxorubicin (DXR) and 4′-epidoxorubicin (4′epiDXR) were tested on a covalently closed circular plasmid. In the presence of a reducing agent (sodium borohydride), DXR and 4′epiDXR produced similar dose-dependent alterations of the electrophoretic pattern of DNA fragments. Since transition metal ions are known to catalyze this effect, the effects of Cu(II)DXR and Cu(II)epiDXR were also tested. When the Cu(II)-anthracycline complexes were formed at a drug: metal ratio of 2∶1, the effect on DNA was more severe than in the case of the free drugs; since copper ions alone were found to be devoid of activity at the concentrations present in the complexes, the effect is attributed to a direct interaction between the complexes and DNA. Cu(II)4′epiDXR proved to be more potent than Cu(II)DXR; this is probably due to the different structures of the two complexes.
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Cova, D., Sassano, M., Monti, E. et al. DNA damage induced by doxorubicin, 4′-epidoxorubicin and their copper(II) complexes. Arch Toxicol 64, 597–598 (1990). https://doi.org/10.1007/BF01971842
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DOI: https://doi.org/10.1007/BF01971842