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. 1976 May;33(5):485–490. doi: 10.1038/bjc.1976.78

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

J L Foster, P J Conroy, A J Searle, R L Willson
PMCID: PMC2024956  PMID: 1276030

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Asquith J. C., Foster J. L., Willson R. L., Ings R., McFadzean J. A. Metronidazole ("Flagyl"). A radiosensitizer of hypoxic cells. Br J Radiol. 1974 Aug;47(560):474–481. doi: 10.1259/0007-1285-47-560-474. [DOI] [PubMed] [Google Scholar]
  2. Begg A. C., Sheldon P. W., Foster J. L. Demonstration of radiosensitization of hypoxic cells in solid tumours by metronidazole. Br J Radiol. 1974 Jul;47(559):399–404. doi: 10.1259/0007-1285-47-559-399. [DOI] [PubMed] [Google Scholar]
  3. Deutsch G., Foster J. L., McFadzean J. A., Parnell M. Human studies with "high dose" metronidazole: a non-toxic radiosensitizer of hypoxic cells. Br J Cancer. 1975 Jan;31(1):75–80. doi: 10.1038/bjc.1975.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Emmerson P. T., Howard-Flanders P. Preferential sensitization of anoxic bacteria to x-rays by organic nitroxide-free radicals. Radiat Res. 1965 Sep;26(1):54–62. [PubMed] [Google Scholar]
  5. HAWES C., HOWARD A., GRAY L. H. CHROMOSOME ABNORMALITY AND RADIATION SENSITIVITY IN STORED ASCITES-TUMOUR CELLS. Mutat Res. 1964 Jul;106:193–201. doi: 10.1016/0027-5107(64)90022-3. [DOI] [PubMed] [Google Scholar]
  6. Hall E. J., Roizin-Towle L. Hypoxic sensitizers: radiobiological studies at the cellular level. Radiology. 1975 Nov;117(2):453–457. doi: 10.1148/117.2.453. [DOI] [PubMed] [Google Scholar]
  7. Ings R. M., McFadzean J. A., Ormerod W. E. The mode of action of metronidazole in Trichomonas vaginalis and other micro-organisms. Biochem Pharmacol. 1974 May 1;23(9):1421–1429. doi: 10.1016/0006-2952(74)90362-1. [DOI] [PubMed] [Google Scholar]
  8. Rauth A. M., Kaufman K. In vivo testing of hypoxic radiosensitizers using the KHT murine tumour assayed by the lung-colony technique. Br J Radiol. 1975 Mar;48(567):209–220. doi: 10.1259/0007-1285-48-567-209. [DOI] [PubMed] [Google Scholar]
  9. Stone H. B., Withers H. R. Tumor and normal tissue response to metronidazole and irradiation in mice. Radiology. 1974 Nov;113(2):441–444. doi: 10.1148/113.2.441. [DOI] [PubMed] [Google Scholar]
  10. Sutherland R. M. Selective chemotherapy of noncycling cells in an in vitro tumor model. Cancer Res. 1974 Dec;34(12):3501–3503. [PubMed] [Google Scholar]
  11. Urtasun R. C., Chapman J. D., Band P., Rabin H. R., Fryer C. G., Sturmwind J. Phase 1 study of high-dose metronidazole: a specific in vivo and in vitro radiosensitizer of hypoxic cells. Radiology. 1975 Oct;117(1):129–133. doi: 10.1148/117.1.129. [DOI] [PubMed] [Google Scholar]
  12. Urtasun R. C., Sturmwind J., Rabin H., Band P. R., Chapman J. D. Letter: "High-dose" metronidazole: a preliminary pharmacological study prior to its investigational use in clinical radiotherapy trials. Br J Radiol. 1974 May;47(557):297–299. doi: 10.1259/0007-1285-47-557-297-c. [DOI] [PubMed] [Google Scholar]
  13. Willson R. L., Cramp W. A., Ings R. M. Metronidazole ('Flagyl'): mechanisms of radiosensitization. Int J Radiat Biol Relat Stud Phys Chem Med. 1974 Dec;26(6):557–569. doi: 10.1080/09553007414551591. [DOI] [PubMed] [Google Scholar]
  14. Willson R. L., Searle A. J. Metronidazole (Flagyl): iron catalysed reaction with sulphydryl groups and tumour radiosensitisation. Nature. 1975 Jun 5;255(5508):498–500. doi: 10.1038/255498a0. [DOI] [PubMed] [Google Scholar]

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