title: Metronidazole (Flagyl): characterization as a cytotoxic drug specific for hypoxic tumour cells.
abstract: The cytocidal properties of metronidazole against hypoxic mammalian cells are described. This chemotherapeutic action has been shown to be dependent on drug concentration and duration of exposure. The x-ray TCD50 for a murine anaplastic carcinoma was reduced from 6081 rad to 4643 rad when animals were given metronidazole orally for 36 h before radiation treatment. The effect is attributed to the direct killing of hypoxic tumour cells by a mechanism analogous to that proposed for the action of the drug on anaerobic micro-organisms. It is concluded that further work with metronidazole as a cytotoxin specific for hypoxic cells is warranted, particularly in view of the reported lack of toxicity associated with the preliminary clinical use of the drug as a radiosensitizer in man.
mesh_terms: D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D000860:Hypoxia; D066298:In Vitro Techniques; D008795:Metronidazole / Q000627:therapeutic use*; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000532:radiotherapy
chemical_list: D008795:Metronidazole