Metronidazole (Flagyl): characterization as a cytotoxic drug specific for hypoxic tumour cells

• Published in: British journal of cancer Vol. 33; no. 5; pp. 485 - 490
• Main Authors: Foster, J L, Conroy, P J, Searle, A J, Willson, R L
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.05.1976
• Subjects: Animals; Carcinoma, Ehrlich Tumor - drug therapy; Cell Survival - drug effects; Cell Survival - radiation effects; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Hypoxia; In Vitro Techniques; Metronidazole - therapeutic use; Mice; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - radiotherapy
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.1976.78

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.