In vitro neurotoxic assessment of antitumour drugs.
We have developed a rapid, specific, in vitro method for quantitatively assessing neurotoxicity of antitumour drugs and related compounds. Using cultures of foetal rat hypothalamic neurones and a staining procedure which specifically identifies neuronal cells, the neurotoxicity of 8 antitumour drugs has been evaluated. The order of neurotoxicity appears to correlate well with their known relative clinical toxicities. Neurotoxicity of the radiosensitizer misonidazole was also identified using this system. This method appears to provide a valuable preclinical screen for neurotoxicity which may be particularly useful in the development of new antitumour drug analogues and radiosensitizers.
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005333:Fetus; D006801:Humans; D007031:Hypothalamus; D008920:Misonidazole / Q000633:toxicity; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats
D000970:Antineoplastic Agents; D008920:Misonidazole