METRONIDAZOLE (FLAGYL) - CHARACTERIZATION AS A CYTOTOXIC DRUG SPECIFIC FOR HYPOXIC TUMOR-CELLS

The cytocidal properties of metronidazole against hypoxic mammalian cells are described. This chemotherapeutic action was dependent on drug concentration and duration of exposure. The X-ray TCD50 [median tumor control dose] for a murine anaplastic carcinoma was reduced from 6081 rad to 4643 rad when mice were given metronidazole orally for 36 h before radiation treatment. The effect is attributed to direct killing of hypoxic tumor cells by a mechanism analogous to that proposed for the action of the drug on anaerobic microorganisms. 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.