Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1983 Aug;48(2):271–278. doi: 10.1038/bjc.1983.182

Enhancement of the action of alkylating agents by single high, or chronic low doses of misonidazole.

N J McNally, M Hinchliffe, J de Ronde
PMCID: PMC2011437  PMID: 6882665

Abstract

Misonidazole (MISO) given as a large single dose enhanced the action of cyclophosphamide (Cy) and melphalan (L-PAM) in two mouse tumours. Below a dose of about 500 mg kg-1 it had no chemosensitizing effect. When MISO was given as a series of small doses by repeat injection over an 8 h period, in order to stimulate human pharmacokinetics, it significantly enhanced the action of Cy in the SA F tumour. It also enhanced the action of Cy and L-PAM in the WHFIB tumour as assayed by tumour cell survival in vitro following treatment in vivo but not when the assay was tumour growth delay. There was no enhancement by MISO of the leukopenia due to Cy or L-PAM. The results suggest that, in some tumours there may be benefit from the combination of clinically relevant MISO doses with alkylating agents. The leucopenia induced by these agents should not be enhanced by the MISO.

Full text

PDF
271

Selected References

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

  1. Brown J. M., Hirst D. G. Effect of clinical levels of misonidazole on the response of tumour and normal tissues in the mouse to alkylating agents. Br J Cancer. 1982 May;45(5):700–708. doi: 10.1038/bjc.1982.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown J. M. The mechanisms of cytotoxicity and chemosensitization by misonidazole and other nitroimidazoles. Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):675–682. doi: 10.1016/0360-3016(82)90711-8. [DOI] [PubMed] [Google Scholar]
  3. Conroy P. J., Sutherland R. M., Passalacqua W. Misonidazole cytotoxicity in vivo: a comparison of large single doses with smaller doses and extended contact of the drug with tumor cells. Radiat Res. 1980 Jul;83(1):169–189. [PubMed] [Google Scholar]
  4. Denekamp J., McNally N. J. The magnitude of hypoxic cell cytotoxicity of misonidazole in human tumours. Br J Radiol. 1978 Sep;51(609):747–748. doi: 10.1259/0007-1285-51-609-747. [DOI] [PubMed] [Google Scholar]
  5. George K. C., Hirst D. G., McNally N. J. Effect of hyperthermia on cytotoxicity of the radiosensitizer Ro-07-0582 in a solid mouse tumour. Br J Cancer. 1977 Mar;35(3):372–375. doi: 10.1038/bjc.1977.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Law M. P., Hirst D. G., Brown J. M. Enhancing effect of misonidazole on the response of the RIF-1 tumour to cyclophosphamide. Br J Cancer. 1981 Aug;44(2):208–218. doi: 10.1038/bjc.1981.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Martin W. M., McNally N. J., De Ronde J. Enhancement of the effect of cytotoxic drugs by radiosensitizers. Br J Cancer. 1981 Jun;43(6):756–766. doi: 10.1038/bjc.1981.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McNally N. J., George K. C., de Ronde J. Recovery from sublethal damage by acutely hypoxic tumour cells in vivo and in vitro. Br J Radiol. 1979 Aug;52(620):642–649. doi: 10.1259/0007-1285-52-620-642. [DOI] [PubMed] [Google Scholar]
  9. McNally N. J., Stephens T. C., Twentyman P. R., Hinchliffe M., Peacock J. H., Spooner D. The effect of cytotoxic drugs with or without misonidazole on leucopenia in three strains of mice. Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):659–662. doi: 10.1016/0360-3016(82)90707-6. [DOI] [PubMed] [Google Scholar]
  10. Moore B. A., Palcic B., Skarsgard L. D. Radiosensitizing and toxic effects on the 2-nitroimidazole Ro-07-0582 in hypoxic mammation cells. Radiat Res. 1976 Sep;67(3):459–473. [PubMed] [Google Scholar]
  11. Tannock I. F. In vivo interaction of anti-cancer drugs with misonidazole or metronidazole: cyclophosphamide and BCNU. Br J Cancer. 1980 Dec;42(6):871–880. doi: 10.1038/bjc.1980.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Taylor Y. C., Bump E. A., Brown J. M. Studies on the mechanism of chemosensitization by misonidazole in vitro. Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):705–708. doi: 10.1016/0360-3016(82)90717-9. [DOI] [PubMed] [Google Scholar]
  13. Twentyman P. R., Workman P. An investigation of the possibility of chemosensitization by clinically achievable concentrations of misonidazole. Br J Cancer. 1983 Feb;47(2):187–194. doi: 10.1038/bjc.1983.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Urtasun R. C., Band P., Chapman J. D., Rabin H. R., Wilson A. F., Fryer C. G. Clinical phase I study of the hypoxic cell radiosensitizer RO-07-0582, a 2-nitroimidazole derivative. Radiology. 1977 Mar;122(3):801–804. doi: 10.1148/122.3.801. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES