Doxorubicin‐induced oxygen free radical formation in sensitive and doxorubicin‐resistant variants of rat glioblastoma cell lines

FEBS Letters

Sinha, Birandra K.²  Robert, Jacques¹  Benchekroun, M.Nabil¹ 

[1] Département de Biochimie Médicale et Biologie moléculaire, Université de Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux-Cédex, France;Biochemical & Molecular Pharmacology Section, Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

关键词: Anthracycline;    Electron spin resonance spectroscopy;    Free radical;    Anticancer drug;    Redox activation;    Lipid peroxidation;   

DOI  :  10.1016/0014-5793(93)81589-R

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown