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Doxorubicin‐induced oxygen free radical formation in sensitive and doxorubicin‐resistant variants of rat glioblastoma cell lines
Author(s) -
Benchekroun M.Nabil,
Sinha Birandra K.,
Robert Jacques
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81815-h
Subject(s) - doxorubicin , superoxide dismutase , chemistry , catalase , cell culture , microbiology and biotechnology , glutathione reductase , peroxidase , vincristine , cytochrome c , reactive oxygen species , biochemistry , apoptosis , glutathione peroxidase , enzyme , biology , medicine , chemotherapy , cyclophosphamide , genetics
We have studied the formation of hydroxyl radical (OH • ) induced by doxorubicin in a series of doxorubicin‐ or vincristine‐selected variants of C6 rat glioblastoma cells in culture by electron‐spin resonance spectroscopy using 5,5′‐dimethyl‐1‐pyrroline‐1‐oxide as a spin trap. Wild‐type cells, sensitive to doxorubicin, exhibited in the presence of this drug a concentration‐dependent OH • formation which could be inhibited by preincubation with superoxide dismutase, catalase or an antibody against cytochrome P450‐reductase. In highly doxorubicin‐resistant cells, OH • formation was reduced to about 20% of the level obtained in sensitive cells. In cells presenting a very low level of resistance to doxorubicin or in cells selected with vincristine, both presenting a pure multidrug‐resistant phenotype, OH • formation was identical to that obtained in sensitive cells. In cells of intermediate resistance or in revertant cells, intermediate levels of OH • formation were obtained. Protection against OH • formation and action can be identified at the levels of superoxide dismutase and glutathione peroxidase activities, which are both enhanced in the resistant cells.