Characterization of free radicals produced during oxidation of etoposide (VP-16) and its catechol and quinone derivatives. An ESR Study.
Spectroscopic evidence for the radical-mediated metabolism of VP-16, VP-16 catechol, and VP-16 quinone during enzymatic oxidation and autoxidation has been obtained. Autoxidation of the catechol yields the primary semiquinone together with the primary molecular product VP-16 quinone, which subsequently undergoes hydrolytic oxidation to form secondary quinones and semiquinones. Both primary and secondary phenoxyl radicals were detected during peroxidatic oxidation of VP-16. Neither the primary nor the secondary radicals react with DNA at a detectable rate. Evidence for the production of hydroxyl radical during iron-catalyzed oxidation of VP-16 catechol was obtained. These free radical reactions may have implications for the mechanism of antitumor action of VP-16.
Kalyanaraman
B
B
National Biomedical ESR Center, Medical College of Wisconsin, Milwaukee 53226.
Nemec
J
J
Sinha
B K
BK
D002396:Catechols / Q000378:metabolism*; D003198:Computer Simulation; D004247:DNA / Q000032:analysis; D004249:DNA Damage; D004578:Electron Spin Resonance Spectroscopy; D005047:Etoposide / Q000031:analogs & derivatives / Q000378:metabolism*; D005609:Free Radicals; D006878:Hydroxides / Q000032:analysis; D008433:Mathematics; D010084:Oxidation-Reduction; D010636:Phenols / Q000032:analysis; D011809:Quinones / Q000378:metabolism*
D002396:Catechols; D005609:Free Radicals; D006878:Hydroxides; D010636:Phenols; D011809:Quinones; D005047:Etoposide; D004247:DNA