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Doxorubicin‐mediated free radical generation in intact human tumor cells enhances nitroxide electron paramagnetic resonance absorption intensity decay
Author(s) -
Voest E. E.,
Van Faassen E.,
Neijt J. P.,
Marx J. J. M.,
Van Asbeck B. S.
Publication year - 1993
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.1910300303
Subject(s) - doxorubicin , chemistry , deferoxamine , intracellular , electron paramagnetic resonance , superoxide dismutase , biophysics , nuclear magnetic resonance , biochemistry , biology , medicine , chemotherapy , oxidative stress , physics
The decay of nitroxide spin label electron paramagnetic resonance (EPR) absorption intensity was used to investigate the doxorubicin‐mediated intracellular generation of free radicals. The effects of 50–500 μg/ml doxorubicin on human tumor cells (MCF‐7, breast cancer cells, and HL‐60, promyelocytic leukemia, cells) were studied by measuring 2,2,6,64etramethylpip‐eridine‐1‐oxyl (TEMPO) absorption intensity decay (TAID) at a TEMPO concentration of 10 μM. Doxorubicin accelerated the TAID in both cell lines with a detection limit of 50 μg/ml for MCF‐7 cells and 500 μg/ml doxorubicin for HL‐60 cells. Preincubation of cells with the iron chelating agent, deferoxamine (5 mM), partially prevented the effects of doxorubicin on the TAID. Catalase and copper, zinc‐superoxide dismutase (Cu, Zn‐SOD) had no influence on the effects of doxorubicin on the TAID in intact cells. However, Cu, Zn‐SOD completely abolished the effects of doxorubicin on the TAID in a MCF‐7 cell‐free system. Our findings suggest that doxorubicin mediates the intracellular generation of O 2 and that iron is involved in this process.