Coppier ion-dependent oxy-radical mediated DNA damage from dihydroxy derivative of etoposide |
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| Authors: | Birandra K. Sinha William M. Antholine B. Kalyanaraman Helen M. Eliot |
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| Affiliation: | 1. Biochemical Pharmacology Section, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD U.S.A.;2. National Biomedical ESR Center, Milwaukee, WI U.S.A. |
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| Abstract: | The dihydroxy etoposide, a metabolite of the clinically active anticancer drug, VP-16, induced extensive DNA damage in the presence of copper ions. While superoxide dismutase was without any effect on the DNA damage, catalase and inhibitors of free hydroxyl radicals inhibited the DNA degradation, indicating that hydroxyl radicals were responsible for this drug-Cu-dependent DNA damage. |
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| Keywords: | DNA damage Copper Hydroxyl radical VP-16-Q DHVP the 3′-hydroxy VP-16 DTT dithiothreitol DMPO 5,5-dimethyl-1-pyrroline oxide ESR electron spin resonance SOD superoxide dismutase PEG poly(ethylene glycol) DETAPAC diethylenetriaminepentaacetic acid |
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