Nitroimidazoles as Hypoxia-Mediated Drugs in Cancer Chemotherapy
There is abundant evidence that human tumours, even of quite small size (2 mm) contain a significant proportion of cells that are deficient in oxygen CD. These hypoxic cells are radiation-resistant and are believed to limit in some instances the effectiveness of the treatment of cancer by radiotherapy. Several of the papers presented in this Conference have discussed how nitroimidazoles might be used to overcome this problem by specifically increasing the radiation sensitivity of the resistant hypoxic cells. This paper is concerned, however, with the potential use of nitroimidazoles in cancer chemotherapy.
KeywordsCytotoxic Drug Hypoxic Cell Enhancement Ratio Radiation Sensitizer Chinese Hamster Cell
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- 8.E. Smith, The influence of hypoxia on the cytotoxic response of Chinese hamster cells, Ph.D. Thesis, University of London (1981).Google Scholar
- 11.G. E. Adams, К. B. Dawson and I. J. Stratford, Electron-affinie radiation sensitizers for hypoxic cells: prospects and limitations with present and future drugs, in: Proc. Int. Meeting for Radio-Oncology, May 1978, Vienna, Georg Thiéme, Stuttgart:84 (1980).Google Scholar
- 19.R. M. Sutherland, The multicellular spheroid system as a tumour model for studies of radiation sensitizers, Pharmac. Ther. 8:105 (1980).Google Scholar
- 23.C. M. Rose, J. L. Millar, J. H. Peacock, T. A. Phelps and T. C. Stephens, Differential enhancement of melphalan cytotoxicity in tumour and normal tissue by misonidazole, ins “Radiation Sensitizers: Their use in the clinical management of cancer,” Cancer Management Vol. 5, éd., L. W. Brady, Masson, New York (1980) p. 250.Google Scholar
- 29.M. P. Law, D. G. Hirst and J. M. Brown, The enhancing effect of misonidazole on the response of the RIF 1 tumour to cyclophosphamide, Br. J. Cancer in press (1981).Google Scholar
- 31.R. T. Mulcahy, D. W. Siemann and R. M. Sutherland, In vivo response of KHT sarcomas to combination chemotherapy with radiosensitizers and BCNU, Br. J. Cancer 43:93 (1981).Google Scholar
- 33.R. Clutterbuck, J. L. Millar and T. McElwain, Misonidazole enhancement of the action of BCNU and melphalan against human melanoma xenografts, Cancer Clin. Trials 4: in press (1981).Google Scholar
- 34.G. E. Adams, C. Clarke, К. B. Dawson, P. W. Sheldon and I. J. Stratford, Nitroimidazoles as hypoxic cell radiation sensitizers and cytotoxic agents, Proc. 2nd Int. Symposium: Biological Bases and Clinical Implications of Tumour Resistance, Rome, Italy, September 21–24 (1980).Google Scholar
- 39.E. Smith, I. J. Stratford and G. E. Adams, Misonidazole enhancement of the cytotoxic action of melphalan in vitro, Br. J. Cancer, submitted (1981).Google Scholar
- 40.M. E. Varnes, J. E. Biaglow, C. J. Koch and E. J. Hall, Depletion of nonprotein thiols of hypoxic cells by misoni-dazole and metronidazole, in: “Radiation Sensitizers: Their use in the clinical management of cancer,” Cancer Management vol. 5, ed. L. W. Brady, Masson, New York, (1980) p. 121.Google Scholar