We have obtained biochemical evidence that misonidazole when administered in large doses to rats produces a sparse dying-back peripheral neuropathy and degenerative changes in the trigeminal ganglia and cerebellum. In our experience these neurotoxic effects of misonidazole cannot be detected reliably by the use of simple behavioural and functional tests, e.g., inclined plane and narrowing bridge tests (Rose and Dewar, unpublished results). Therefore, these methods would be of limited use in the neurotoxicity screening of misonidazole analogues. On the other hand, the biochemical approach provides a convenient quantitative method which could be used as the basis for comparing the neurotoxicity of other candidate radiosensitizing drugs.
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