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.
Department of Pharmacy, Leicester Polytechnic, UK.
G R
GR
Fisher
L H
LH
Patterson
D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006735:Horseradish Peroxidase / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008942:Mitoxantrone / Q000494:pharmacology*; D010957:Plasmids / Q000187:drug effects
D004277:DNA, Single-Stranded; D005609:Free Radicals; D006861:Hydrogen Peroxide; D008942:Mitoxantrone; D006735:Horseradish Peroxidase