Abstract
A distinguishing feature of solid tumors compared to most, if not all, normal tissues is their regions of low oxygen tension1. Because hypoxic cells are resistant both to radiation-induced cell killing and to the cytotoxic action of some chemotherapeutic drugs, they have long been considered to be a problem for the radiotherapist and, in some cases, for cancer treatment by cytotoxic drugs. More recently, however, tumor hypoxia is beginning to be regarded as a potentially exploitable difference between normal and neoplastic tissue which might be manipulated for therapeutic benefit, and there are a number of different ways in which this might be achieved.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
J. E. Moulder and S. Rockwell, Hypoxic fractions of solid tumors: experimental techniques, methods of analysis, and a survey of existing data, Int. J. Radiat. Oncol. Biol. Phys. 10:695–712 (1984).
M. A. Baker, E. M. Zeman, V. K. Hirst, and J. M. Brown, Metabolism of SR 4233 by Chinese hamster ovary cells: Basis of selective hypoxic cytotoxicity, Cancer Res. 48: 5947–5952 (1988).
E. M. Zeman and J. M. Brown, Modifiers of SR 4233 cytotoxicity, Abstract of 35th Annual Meeting of Radiation Research Society, 1987 (1987).
E. M. Zeman, M. A. Baker, M. J. Lemmon, C. I. Pearson, J. A. Adams, J. M. Brown, W. W. Lee, and M. Tracy, Structure-activity relationships for benzotriazine di-N-oxides, Int. J. Radiat. Oncol. Biol. Phys. 16: 977–981 (1989).
A. J. Varghese and G. F. Whitmore, Detection of a reactive metabolite of misonidazole in human urine, Int. J. Radiat. Oncol. Biol. Phys. 10:1361–1363 (1984).
Y. C. Taylor and A. M. Rauth, Differences in the toxicity and metabolism of the 2-nitroimidazole misonidazole (Ro-07–0582) in HeLa and Chinese hamster ovary cells, Cancer Res. 38:2745–2752 (1978).
K. Laderoute, P. Wardman and A. M. Rauth, Molecular mechanisms for the hypoxia-dependent activation of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233), Biochem. Pharmacol. 37:1487–1495 (1988).
E. M. Zeman and J. M. Brown, Pre- and post-irradiation radio-sensitization by SR 4233, Int. J. Radiat. Oncol. Biol. Phys. 16:967–971 (1989).
K. W. Kohn, L. C. Erickson, R. A. Ewig,, and C. A. Friedman, Fractionation of DNA from mammalian cells by alkaline elution, Biochemistry 15:4629–4637 (1976).
A. Giaccia, R. Weinstein, J. Hu, and T. D. Stamato, Cell-cycle dependent repair of double-strand breaks in the gamma-ray-sensitive Chinese hamster cell, Somat. Cell and Molec. Gent. 11:485–491 (1985).
R. F. Kallman and M. J. Dorie, Tumor oxygenation and reoxygenation during radiation therapy: their importance in predicting tumor response, Int. J. Radiat. Oncol. Biol. Phys. 12:681–685 (1986).
E. M. Zeman, V. K. Hirst, M. J. Lemmon, and J. M. Brown, Enhancement of radiation-induced tumor cell killing by the hypoxic cell toxin SR 4233, Radiother. Oncol. 12:209–218 (1988).
D. B. Cater, C. M. B. Grigson, and D. A. Watkinson, Changes of oxygen tension in tumors induced by vasoconstrictor and vasodilator drugs, Acta Radiol. 58:401–408 (1962).
D. J. Chaplin and B. Acker, The effect of hydralazine on the tumor cytotoxicity of the hypoxic cell cytotoxin RSU-1069: evidence for therapeutic gain, Int. J. Radiat. Oncol. Biol. Phys. 13:579–585 (1987).
D. J. Chaplin, Potentiation of RSU-1069 tumour cytotoxicity by 5-hydroxytryptamine (5-HT), Br. J. Cancer 54:727–731 (1986).
P. F. Dodion, J. Abrams, B. Gerard, N. Crespeigne, B. Peeters, B. C. Van, and Y, Kenis, Clinical and pharmacokinetic phase 1 trial with the diethylaminoester of flavone acetic acid (LM985, NSC 293015), Eur. J. Cancer Clin. Oncol. 23:837–842 (1987).
T. H. Corbett, M. C. Bissery, A. Wozniak, J. Plowman,, L. Polin, E. Tapazoglou, J. Dieckman, and F. Valeriote, Activity of flavone acetic acid (NSC-347512) against solid tumors of mice. Invest. New Drugs 4: 207–220 (1986).
M. C. Bibby, J. A. Double, P. M. Loadman, and C.V. Duke, Reduction of tumor blood flow by flavone acetic acid: A possible component of therapy. J. Natl. Cancer Inst. 81:216–220 (1989).
J. M. Brown, Exploitation of bioreductive agents with vasoactive drugs, Proceedings of the 8th International Conference of Radiation Research, 719–724 (1988).
J. R. Sun and J. M. Brown, Enhancement of the antitumor effect of flavone acetic acid by the bioreductive cytotoxic drug SR 4233, Cancer Res. 49: 5664–5670 (1989).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer Science+Business Media New York
About this chapter
Cite this chapter
Brown, J.M. (1990). Redox Activation of Benzotriazine N-Oxides: Mechanisms and Potential as Anticancer Drugs. In: Adams, G.E., Breccia, A., Fielden, E.M., Wardman, P. (eds) Selective Activation of Drugs by Redox Processes. NATO ASI Series, vol 198. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3768-7_12
Download citation
DOI: https://doi.org/10.1007/978-1-4615-3768-7_12
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6679-9
Online ISBN: 978-1-4615-3768-7
eBook Packages: Springer Book Archive