Induction of Differential Hypoxia in Tissues and its Implications for Therapy

  • G. E. Adams
  • I. J. Stratford


The search for chemical substances that induce radiation protection in tissues has been in progress for many years. Interest has tended to concentrate on small molecules such as simple alcohols, dimethylsulphoxide and in particular, numerous thiols and thiophosphates. Major objectives have been two-fold. Firstly, the development of techniques for protecting individuals from the effects of exposure to whole-body radiation, accidental or otherwise and secondly, clinical strategies for reducing normal tissue morbidity in the radiation therapy of cancer. Several of the papers in these proceedings are concerned with various aspects of these topics. This paper, however, addresses another approach based on manipulation of oxygenation of normal tissues and tumours not only for inducing radiation resistance but also for obtaining increased therapeutic efficacy of some anti-tumour strategies.


Hyperbaric Oxygen Tumour Hypoxia Enhancement Ratio Experimental Tumour Acute Radiation Syndrome 
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  1. 1.
    R.S. Bush, The significance of anaemia in clinical radiation therapy. Int. J. Radiat. Oncol. Biol. Phys., 12, 2047–2050 (1986).PubMedCrossRefGoogle Scholar
  2. 2.
    R.S. Bush, R.D.T. Jenkin, W.E.C. Allt, F.A. Beale, H.A. Bean, A. J. Dembo and J.F. Pringle. Definitive evidence for hypoxic cells influencing cure in cancer therapy. Br. J. Cancer 37 (III), 255–258 (1978).Google Scholar
  3. 3.
    J. Overgaard, S.H. Hansen, K. Jorgensen and M. Hjelm, Primary radiotherapy of larynx and pharynx carcinoma — An analysis of some factors affecting local control and survival. Int. J. Radiat. Oncol. Biol. Phys-. 12, 515–521 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    J. Overgaard, S.H. Hansen, A.P. Anderson, M. Hjelm-Handsen, K. Jorgensen, K. Sandberg, J. Rygard, R.H. Jensen and M. Petersen, Misonidazole as an adjuct to radiotherapy in the treatment of invasive carcinoma of the larynx and pharynx. Proceedings of the 3rd Int. Meeting on Progress in Radio-Oncology, March 1985, Vienna, Austria. Raven Press, New York, 1987, (in press).Google Scholar
  5. 5.
    S. Dische, P.J. Anderson, R. Sealy and E.R. Watson, Carcinoma of the cervix: Anaemia, radiotherapy and hyperbaric oxygen. Br. J. Radiol. 56, 251–255 (1983).PubMedCrossRefGoogle Scholar
  6. 6.
    E.R. Watson, K.E. Hainan, S. Dische, M.I. Saunders, I.S. Cade, J.B. McEwen, G. Wiernik, D.J.D. Perrins and I. Sutherland, Hyperbaric oxygen and radiotherapy: A Medical Research Council trial in carcinoma of the cervix. Br. J. Radiol. 51, 879–887 (1978).PubMedCrossRefGoogle Scholar
  7. 7.
    H.B. Hewitt and E. Blake, Effect of induced host anaemia on the viability and radiosensitivity of murine malignant cells in vivo. Br. J. Cancer 25, 323–336 (1971).PubMedCrossRefGoogle Scholar
  8. 8.
    R.P. Hill, R.S. Bush and P. Yeung, The effect of anaemia on the fraction of hypoxic cells in an experimental tumour. Br. J. Radiol. 299–304 (1971).Google Scholar
  9. 9.
    D.G. Hirst, J.L. Hazelhirst and J.M. Brown, The effect of haemato-crit on tumour sensitivity to X-rays. Int. J. Radiat. Biol. 46, 345–354 (1984).CrossRefGoogle Scholar
  10. 10.
    D.G. Hirst, Anaemia: A problem or opportunity in radiotherapy? Int. J. Radiat. Oncol. Biol. Phys. 12, 2009–2017 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    D.G. Hirst, Oxygen delivery to tumours. Int. J. Radiat. Oncol. Biol. Phys. 12, 1271–1277 (1986).PubMedCrossRefGoogle Scholar
  12. 12.
    C.R. Beddell, P.J. Goodford, G. Kneen, R.D. White, S. Wilkinson and R. Wootton, Substituted benzaldehydes designed to increase the oxygen affinity of human haemoglobin and inhibit the sickling of sickle erythrocytes. Br. J. Pharmacol. 82, 397–407 (1984).PubMedGoogle Scholar
  13. 13.
    G.E. Adams, I.J. Stratford, I. Ahmed and P.W. Sheldon, Some new developments in tumour radiosensitization. Proc “3rd Int. Meeting on Progress in Radio-Oncology”, March27th-30th 1985; Vienna, Austria. Raven Press, New York, 1987 (in press).Google Scholar
  14. 14.
    G.E. Adams, D. Barnes, J. Loutit, S. Cole, P.W. Sheldon, I.J. Stratford, G.J.M.J. Van der Aardweg, J. Hopewell, R. White, G. Kneen, A. Nethersell and C. Edwards, Induction of hypoxia in normal and malignant tissues by changing the oxygen affinity of haemoglobin: Implications for therapy. Int. J. Radiat. Oncol. Biol. Phys. 12, 1299–1302 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    D.J. Chaplin and B. Acker, Potentiation of RSU 1069 tumour cytotoxicity by hydralazine: A new approach to selective therapy. Int. J. Radiat. Oncol. Biol. Phys. 13, 1987 (in press).Google Scholar
  16. 16.
    D.B. Cater, C.M.B. Grigson and D.A. Watkinson, Changes of oxygen tension in tumours induced by vasocontrictor and vasodilator drugs. Acta. Radiol. 58, 401–408 (1962).PubMedCrossRefGoogle Scholar
  17. 17.
    J.A. Kruuv, W.R. Inch and J.A. McCredie, Blood flow and oxygenation of tumours in mice II. Effect of vasodilator drugs. Cancer 20, 60–65 (1967).PubMedCrossRefGoogle Scholar
  18. 18.
    W.H. Knapp, J. Debatin, K. Layer, F. Helus, A. Altmann, H.J. Sinn and H. Ostertag, Selective drug induced reduction of blood flow in tumour transplants. Int. J. Radiat. Oncol. Biol. Phys. 11, 1357–1366 (1985).PubMedCrossRefGoogle Scholar
  19. 19.
    G.E. Adams, I. Ahmed, P.W. Sheldon and I.J. Stratford, Radiation sensitization and chemopotentiation: RSU 1069, a compound more efficient than misonidazole in vitro and in vivo. Br. J. Cancer 49, 571–578 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • G. E. Adams
    • 1
  • I. J. Stratford
    • 1
  1. 1.Medical Research CouncilRadiobiology Unit ChiltonDidcot OxonEngland

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