Benchekroun M N, Sinha B K, Robert J
Département de Biochimie Médicale et Biologie moléculaire, Université de Bordeaux II.
FEBS Lett. 1993 Jul 12;326(1-3):302-5. doi: 10.1016/0014-5793(93)81815-h.
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.
我们通过电子自旋共振光谱法，以5,5'-二甲基-1-吡咯啉-1-氧化物作为自旋捕获剂，研究了阿霉素在一系列培养的C6大鼠胶质母细胞瘤细胞的阿霉素或长春新碱选择变体中诱导产生羟基自由基（OH·）的情况。对阿霉素敏感的野生型细胞在该药物存在下呈现出浓度依赖性的OH·形成，这种形成可通过与超氧化物歧化酶、过氧化氢酶或抗细胞色素P450还原酶抗体预孵育来抑制。在高度耐阿霉素的细胞中，OH·形成减少至敏感细胞中所获水平的约20%。在对阿霉素耐药水平非常低的细胞或用长春新碱选择的细胞中，二者均呈现纯多药耐药表型，OH·形成与敏感细胞中所获情况相同。在中等耐药的细胞或回复细胞中，获得了中等水平的OH·形成。在超氧化物歧化酶和谷胱甘肽过氧化物酶活性水平可发现对OH·形成及作用的保护，这两种酶在耐药细胞中均增强。
