MODIFICATION OF THE AEROBIC CYTOTOXICITY OF ETANIDAZOLE

Purpose: To determine the feasibility of modifying the aerobic cytotox icity of etanidazole without interfering with the tumoricidal action o f radiation plus etanidazole. Methods and Materials: The aerobic cytot oxicity of etanidazole was studied using two different models: (1) Ind uction of apoptosis in EL4 cells: apoptotic DNA fragmentation was anal yzed by agarose gel electrophoresis following 24 h treatment with etan idazole alone or in combination with various modifiers. (2) Spinal cor d neuronal loss in organotypic roller tube cultures: Survival of acety lcholinesterase positive ventral horn neurons was analyzed morphometri cally following 72 h treatment with etanidazole alone or in combinatio n with vitamin E succinate. Results: EtanidazoIe (10 mM) induced apopt osis in EL4 cells. This effect was suppressed by 24 h treatment with T PA, IBMX, the free radical scavenger TEMPOL or vitamin E succinate. Vi tamin E succinate also protected spinal cord cultures from etanidazole -induced neuronal loss. Conclusion: These results suggest that it migh t be possible to modify the neurotoxicity of etanidazole with agents t hat would not be expected to interfere with the tumoricidal action of radiation plus etanidazole.