2 research outputs found
Fe-EDTA-Bisamide and Fe-ADR-925, The Iron-Bound Hydrolysis Product of the Cardioprotective Agent Dexrazoxane, Cleave DNA Via the Hydroxyl Radical
Use of the antitumor drug doxorubicin is limited by cardiomyopathic side-effects
which are believed to be due to iron-mediated hydroxyl radical generation. Dexrazoxane
reduces this cardiotoxicity, possibly by removal of iron from doxorubicin by the EDTA-like
hydrolysis product of dexrazoxane, ADR-925. However, EDTA-diimides like dexrazoxane,
previously used as antitumor agents, are themselves carcinogenic, and recent studies have
found that Fe-ADR-925 can also promote hydroxyl radical production. This study
demonstrates that, like Fe-EDTA, Fe-ADR-925 and a related desmethyl complex can cleave
plasmid DNA under Fenton conditions, and suggests by radical scavenger study that this
cleavage is probably via the hydroxyl radical. Differences in DNA cleavage dependence
upon concentrations of Fe-EDTA, Fe-ADR-925 and Fe-EDTA-bisamide can be explained by differences in the solution chemistry of the complexes