DNA strand breakage by peroxidase-activated mitoxantrone.

Spectroscopic evidence demonstrate that the alkylaminoanthraquinone mitoxantrone is a substrate for horseradish peroxidase in the presence of hydrogen peroxide and that the result of this interaction is the formation of an air-stable mitoxantrone-derived free radical. The mitoxantrone-derived free radicals or their further oxidation products appear to extensively cross-link with plasmid DNA by a reaction that is mitoxantrone concentration-dependent. Oxidative activation of mitoxantrone to a DNA-damaging species may contribute to the mechanism of action of this antitumour agent.