Skip to main content
SpringerLink
Log in

Radiation Sensitizers and Related Compounds: New Approaches to Modification of Radiation Response

  • Conference paper
Radiobiology in Radiotherapy

  • 168 Accesses

Abstract

The hypothesis that the relative radiation resistance of hypoxic tumour cells present in some human tumours can adversely affect the probability of local control in some clinical situations, remains a major research topic. There is some clinical evidence, mainly from studies using hyperbaric oxygen, that hypoxic cell resistance is a factor in the local control of some tumours. However, it is widely believed that tumour hypoxia is probably only important in some tumours; in others, reoxygenation occurring between fractions many effectively remove hypoxic cells during treatment. It is against the background of this heterogeneity with respect to the importance of hypoxia that attempts to demonstrate clinical radiation sensitization have been carried out. In retrospect, therefore, it is perhaps not surprising that the results of clinical trials with misonidazole have been generally disappointing. An urgent need is to develop methods of identifying those human tumours where hypoxic cell radioresistance is a problem. When such techniques become available the clinical efficacy of any new and improved sensitizer should be much more easily demonstrable.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adams GE, Dewey DL (1963) Hydrated electrons and radiobiological sensitization. Biochem Biophys Res Comm 12: 473–477

    Article  PubMed  CAS  Google Scholar 

  • Adams GE, Stratford IJ (1987) Sensitization of anti-cancer agents. In: Dubois JB, Joyeux H, Serrou B (eds) Colorectal, ovarian, liver cancer. Colloq INSERM 150: 151–162

    Google Scholar 

  • Adams GE, Flockhart IR, Smithen CE, Stratford IJ, Wardman P, Watts ME (1976) Electron-affinic sensitization. 7. A correlation between structure, one-electron reduction potentials and efficiencies of nitroimidazoles as hypoxic cell radiosensitizers. Radiat Res 67: 9–20

    Article  PubMed  CAS  Google Scholar 

  • Adams GE, Clarke ED, Flockhart IR et al. (1979) Structure-activity relationships in the development of hypoxic cell radiosensitizers. 1. Sensitizing efficiency. Int J Radiat Biol 35: 133–150

    Article  CAS  Google Scholar 

  • Adams GE, Ahmed I, Sheldon PW, Stratford IJ (1984a) Radiation sensitization and chemopotentiation: RSU 1069, a compound more efficient than misonidazole in vitro and in vivo. Br J Cancer 49: 571–578

    Article  PubMed  CAS  Google Scholar 

  • Adams GE, Ahmed I, Sheldon PW, Stratford IJ (1984b) RSU 1069, a 2-nitroimidazole containing an alkylating group: high efficiency as a radio- and chemosensitizer in vitro and in vivo. Int J Radiat Oncol Biol Phys 10: 1653–1656

    Article  PubMed  CAS  Google Scholar 

  • Adams GE, Barnes D, Loutit J et al. (1986) 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

    Article  PubMed  CAS  Google Scholar 

  • Alexander P (1986) Bioreduction in the activation of drugs. Biochem Pharmacol 35: 1–122

    Article  Google Scholar 

  • Beddell CR, Goodford PJ, Kneen G, White RD, Wilkinson S, Wootton R (1984) Substituted benzaldehydes designed to increase the oxygen affinity of human haemoglobin and inhibit the sickling of sickle erythrocytes. Br J Pharmacol 82: 397–407

    PubMed  CAS  Google Scholar 

  • Biaglow JE, Varnes ME, Clark EP, Epp ER (1983) The role of thiols in cellular response to radiation and drugs. Radiat Res 95: 437–455

    Article  PubMed  CAS  Google Scholar 

  • Brown JM (ed) (1986) Chemical modifiers of cancer treatment. Int J Radiat Oncol Biol Phys 12: 1019–1545

    Google Scholar 

  • Brown JM, Workman P (1980) Partition coefficient as a guide to the development of radiosensitizers which are less toxic than misonidazole. Radiat Res 82: 171–190

    Article  PubMed  CAS  Google Scholar 

  • Brown JM, Yu NY, Brown DM, Lee W (1981) SR 2508: a 2-nitroimidazole amide which should be superior to misonidazole as a radiosensitizer for clinical use. Int J Radiat Oncol Biol Phys 7: 695–703

    Article  PubMed  CAS  Google Scholar 

  • Bump EA, Yu NN, Brown JM (1982) The use of drugs which deplete intracellular glutathione as radiosensitizers of hypoxic tumour cells in vivo. Int J Radiat Oncol Biol Phys 8: 439–442

    Article  PubMed  CAS  Google Scholar 

  • Bush RS, Jenkin RDT, Allt WEC et al. (1978) Definitive evidence for hypoxic cells influencing curve in cancer therapy. Br J Cancer 37 [III]: 255–258

    Google Scholar 

  • Chaplin DJ, Acker B (1987) Potentiation of RSU 1069 tumour cytotoxicity by hydralazine: a new approach to selective therapy. Int J Radiat Oncol Biol Phys 13 (in press)

    Google Scholar 

  • Chapman JD, Ngan-Lee J, Stobbe CC, Meeker B (1982) Radiation-induced metabolism induced reactions of hypoxic sensitizers with cellular macromolecules. In Breccia A, Rimondi C, Adams GE (eds) Advanced topics on radiation sensitizers of hypoxic cells. Plenum, New York, pp 91–100 (Nato advanced study series, vol A43 )

    Google Scholar 

  • Clarke C, Dawson KB, Sheldon PW, Ahmed I (1982) Neurotoxicity of radiation sensitizers in the mouse. Int J Radiat Oncol Biol Phys 8: 787–790

    Article  PubMed  CAS  Google Scholar 

  • Coleman CN, Urtason RC, Wasserman TH et al. (1984) Initial report of the phase I trial of the hypoxic cell radiosensitizer SR 2508. Int J Radiat Oncol Biol Phys 10: 1749–1753

    Article  PubMed  CAS  Google Scholar 

  • Dennis MF, Stratford MRL, Wardman P, Watts ME (1985) Cellular uptake of misonidazole and analogues with acidic or basic functions. Int J Radiat Biol 47: 629–643

    Article  CAS  Google Scholar 

  • Dische S, Saunders MI, Lee ME, Adams GE, Flockhart IR (1977) Clinical testing of the radiosensitizer Ro 07-0582: experience with multiple doses. Br J Cancer 35: 567–579

    Article  PubMed  CAS  Google Scholar 

  • Dische S, Anderson PJ, Sealy R, Watson ER (1983) Carcinoma of the cervix: anaemia, radiotherapy and hyperbaric oxygen. Br J Radiol 56: 251–255

    Article  PubMed  CAS  Google Scholar 

  • Dische S, Saunders MI, Bennett MH et al. (1986) A comparison of the tumour concentrations obtainable with misonidazole and Ro 03-8799. Br J Radiol 59: 911–917

    Article  PubMed  CAS  Google Scholar 

  • Griffith OW, Meister A (1979) Potent and specific inhibition of gluthathione synthesis by buthionine sulphoximine (S-n-butyl homocysteine sulphoximine). J Biol Chem 254: 7558–7560

    PubMed  CAS  Google Scholar 

  • Guichard M, de Langen-Omri F, Malaise EP (1979) Influence of misonidazole on the radiosensitivity of a human melanoma in nude mice: time dependent increase in surviving fraction. Int J Radiat Oncol Biol Phys 5: 487–489

    CAS  Google Scholar 

  • Hall EJ, Biaglow JE (1977) Ro-07-0582 as a radiosensitizer and cytotoxic agent. Int J Radiat Oncol Biol Phys 2: 521–530

    Article  PubMed  CAS  Google Scholar 

  • Harris JW (1979) Mammalian cell studies with Diamide. Pharmacol Ther 7: 375–384

    Article  PubMed  CAS  Google Scholar 

  • Hewitt HB, Blake E (1971) Effect of induced host anaemia on the viability and radiosensitivity of murine malignant cells in vivo. Br J Cancer 25: 323–336

    Article  PubMed  CAS  Google Scholar 

  • Hill RP, Bush RS, Yeung P (1971) The effect of anaemia on the fraction of hypoxic cells in an experimental tumour. Br J Radiol 44: 299–304

    Article  PubMed  CAS  Google Scholar 

  • Hirst DG (1986) Anaemia: a problem or opportunity in radiotherapy? Int J Radiat Oncol Biol Phys 12: 2009–2017

    Article  PubMed  CAS  Google Scholar 

  • Hirst DG, Hazelhurst JL, Brown JM (1984) The effect of alterations in haematocrit on tumour sensitivity to X-rays. Int J Radiat Biol 46: 345–354

    Article  CAS  Google Scholar 

  • Nakagawa K, Tsunemoto H, Watanabe I (1983) Effect of misonidazole and the radiosensitivity and repair of potentially lethal damage of L5178Y Ascites Tumour Cells. Curr J Cancer Clin Oncol 19: 527–532

    Article  CAS  Google Scholar 

  • Overgaard J, Hansen SH, Jorgensen K, Hjelm M (1986) 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

    Article  PubMed  CAS  Google Scholar 

  • Overgaard J, Hansen SH, Anderson AP et al. (1987) Misonidazole as an adjunct to radiotherapy in the treatment of invasive carcinoma of the larynx and pharynx. Proceedings of the 3rd international meeting on progress in radio-oncology, Vienna, Austria, March 1985. Raven Press, New York pp 137–147

    Google Scholar 

  • Raleigh JA, Chapman JD, Borsa J, Kremers W, Reuvers AP (1973) Radiosensitization of mammalian cells by p-nitroacetophenone. 3. Effectiveness of nitrobenzene analogues. Int J Radiat Biol 23: 377–387

    Article  CAS  Google Scholar 

  • Roberts IT, Bleehen NM, Workman P, Walton MI (1984) A phase I study of the hypoxic cell radiosensitizer Ro-03-8799. Int J Radiat Oncol Biol Phys 10: 1755–1758

    Article  PubMed  CAS  Google Scholar 

  • Saunders MI, Anderson PJ, Bennett MH et al. (1984) The clinical testing of Ro 03-8799: pharmacokinetics, toxicology, tissue and tumour concentrations. Int J Radiat Oncol Biol Phys 10: 1759–1763

    Article  PubMed  CAS  Google Scholar 

  • Smithen CE, Clarke ED, Dale JA et al. (1980) Novel (nitro-l-imidazolyl)-alkanolamines as potential radiosensitizers with improved therapeutic properties. In: Brady LW (ed) Radiation sensitizers: their use in the clinical management of cancer. Masson, New York, pp 22–32

    Google Scholar 

  • Stratford IJ, Adams GE, Horsman MR et al. (1980) The interaction of misonidazole with radiation, chemotherapy agents, or heat: a preliminary report. Cancer Clin Trials 3: 231–236

    PubMed  CAS  Google Scholar 

  • Stratford IJ, O’Neill P, Sheldon PW, Silver ARJ, Walling JM, Adams GE (1986) RSU 1069, a nitroimidazole containing an aziridine group: bioreduction greatly increases cytotoxicity under hypoxic conditions. Biochem Pharmacol 36: 105–109

    Article  Google Scholar 

  • Stratford IJ, Adams GE, Bowler J, Embling PW, Godden J, Howells N (1987a) Induction of tumour hypoxia post-irradiation: a method for increasing the sensitizing efficiency of misonidazole and RSU 1069 in vivo. Int J Radiat Biol (submitted)

    Google Scholar 

  • Stratford IJ, Adams GE, Embling P, Godden J, Nolan J, Timpson N (1987b) Potentiation of the anti-tumour effect of melphalan by the vaso-active drug, hydralazine. Br J Cancer (submitted)

    Google Scholar 

  • Walling JM, Stratford IJ, Stephens M, Adams GE (1987) Dual function radiation sensitizers and bioreductive drugs: factors affecting cellular uptake and sensitizing efficiency in analogues of RSU 1069. Int J Radiat Biol (submitted)

    Google Scholar 

  • Wardman P (1982) Molecular structure and biological activity of hypoxic cell radiosensitizers and hypoxia specific cytotoxins. In: Breccia A, Rimondi C, Adams GE (eds) Advanced topics on radiosensitizers of hypoxic cells. Plenum, New York, pp 49–76 (NATO advanced study institutes series A43 )

    Google Scholar 

  • Watson ER, Hainan KE, Dische S et al. (1978) Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the cervix. Br J Radiol 51: 879–887

    Article  PubMed  CAS  Google Scholar 

  • Watts ME, Jones NR (1985) The effect of extracellular pH on radiosensitization by misonidazole and acidic or basic analogues. Int J Radiat Biol 47: 645–653

    Article  CAS  Google Scholar 

  • Williams MV, Denekamp J, Minchinton Al, Stratford MRL (1982) In vivo assessment of basic 2-nitroimidazole radiosensitizers. Br J Cancer 46: 127–137

    Article  PubMed  CAS  Google Scholar 

  • Wong TW, Whitmore GF, Gulyas S (1978) Studies on the toxicity and radiosensitizing ability of misonidazole under conditions of prolonged incubation. Radiat Res 75: 541–555

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. G. Adams
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. J. Stratford
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Cambridge School of Clinical Medicine, Department of Clinical Oncology and Radiotherapeutics, Addenbrooke’s Hospital, Hills Road, CB2 2QQ, Cambridge, UK

    Norman M. Bleehen FRCP, FRCR, Honorary FACR (Cancer Research Campaign Professor of Clinical Oncology, Honorary Director MRC Clinical Oncology and Radiotherapeutics Unit) (Cancer Research Campaign Professor of Clinical Oncology, Honorary Director MRC Clinical Oncology and Radiotherapeutics Unit)

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Adams, G., Stratford, I.J. (1988). Radiation Sensitizers and Related Compounds: New Approaches to Modification of Radiation Response. In: Bleehen, N.M. (eds) Radiobiology in Radiotherapy. Springer, London. https://doi.org/10.1007/978-1-4471-1603-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-1603-5_14

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-1605-9

  • Online ISBN: 978-1-4471-1603-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation