Modification of the aerobic cytotoxicity of etanidazole

Abstract

Purpose : To determine the feasibility of modifying the aerobic cytotoxicity of etanidazole without interfering with the tumoricidal action of radiation plus etanidazole. Methods and Materials : The aerobic cytotoxicity of etanidozole was studied using two different models: (1) Induction of apoptosis in EL4 cells: apoptotic DNA fragmentation was analyzed by agarose gel electrophoresis following 24 h treatment with etanidazole alone or in combination with various modifiers. (2) Spinal cord neuronal loss in organotypic roller tube cultures: Survival of acetylcholinesterase positive ventral horn neurons was analyzed morphometrically following 72 h treatment with etanidazole alone or in combination with vitamin E succinate. Results : Etanidazole (10 mM) induced apoptosis in EL4 cells. This effect was suppressed by 24 h treatment with TPA, IBMX, the free radical scavenger TEMPOL or vitamin E succinate. Vitamin E succinate also protected spinal cord cultures from etanidazole-induced neuronal loss. Conclusion : These results suggest that it might be possible to modify the neurotoxicity of etanidazole with agents that would not be expected to interfere with the tumoricidal action of radiation plus etanidazole.