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Grimes DR, Partridge M. A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio. Biomed Phys Eng Express. 2015;1(4):045209doi: 10.1088/2057-1976/1/4/045209.
Grimes, D. R., & Partridge, M. (2015). A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio. Biomedical physics & engineering express, 1(4), 045209. https://doi.org/10.1088/2057-1976/1/4/045209
Grimes, David Robert, and Partridge, Mike. "A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio." Biomedical physics & engineering express vol. 1,4 (2015): 045209. doi: https://doi.org/10.1088/2057-1976/1/4/045209
Grimes DR, Partridge M. A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio. Biomed Phys Eng Express. 2015 Dec 04;1(4):045209. doi: 10.1088/2057-1976/1/4/045209. PMID: 26925254; PMCID: PMC4765087.
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Biomed Phys Eng Express. 2015 Dec 04;1(4):045209. doi: 10.1088/2057-1976/1/4/045209.

A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio.

Biomedical physics & engineering express

David Robert Grimes, Mike Partridge

Affiliations

  1. Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Gray Laboratory, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford OX3 7DQ, UK.

PMID: 26925254 PMCID: PMC4765087 DOI: 10.1088/2057-1976/1/4/045209

Abstract

The presence of oxygen in tumours has substantial impact on treatment outcome; relative to anoxic regions, well-oxygenated cells respond better to radiotherapy by a factor 2.5-3. This increased radio-response is known as the oxygen enhancement ratio. The oxygen effect is most commonly explained by the oxygen fixation hypothesis, which postulates that radical-induced DNA damage can be permanently 'fixed' by molecular oxygen, rendering DNA damage irreparable. While this oxygen effect is important in both existing therapy and for future modalities such a radiation dose-painting, the majority of existing mathematical models for oxygen enhancement are empirical rather than based on the underlying physics and radiochemistry. Here we propose a model of oxygen-enhanced damage from physical first principles, investigating factors that might influence the cell kill. This is fitted to a range of experimental oxygen curves from literature and shown to describe them well, yielding a single robust term for oxygen interaction obtained. The model also reveals a small thermal dependency exists but that this is unlikely to be exploitable.

Keywords: oxygen; oxygen effect; radiation damage; radiotherapy

References

  1. Stroke. 2002 Jul;33(7):1759-62 - PubMed
  2. PLoS One. 2014 Oct 23;9(10):e110333 - PubMed
  3. Cancer Metastasis Rev. 2007 Jun;26(2):225-39 - PubMed
  4. Int J Hyperthermia. 2004 Mar;20(2):131-9 - PubMed
  5. Radiat Res. 1982 Apr;90(1):126-41 - PubMed
  6. Radiat Res. 1958 Oct;9(4):422-37 - PubMed
  7. Radiat Res. 1957 Nov;7(5):518-40 - PubMed
  8. Br J Radiol. 1953 Dec;26(312):638-48 - PubMed
  9. Br J Radiol. 1972 Jul;45(535):515-24 - PubMed
  10. Int J Radiat Biol Relat Stud Phys Chem Med. 1974 Oct;26(4):383-9 - PubMed
  11. Radiat Res. 1984 Apr;98 (1):141-53 - PubMed
  12. Recent Results Cancer Res. 1987;104:71-109 - PubMed
  13. Jpn J Surg. 1988 May;18(3):276-83 - PubMed
  14. R Soc Open Sci. 2014 Sep 24;1(1):140080 - PubMed
  15. Am J Physiol. 1990 Jun;258(6 Pt 1):G910-8 - PubMed
  16. J R Soc Interface. 2014 Jan 15;11(92):20131124 - PubMed
  17. Radiat Res. 1981 May;86(2):325-40 - PubMed
  18. Nat Rev Cancer. 2011 Jun;11(6):393-410 - PubMed
  19. Cancer Lett. 2003 May 30;195(1):1-16 - PubMed
  20. Science. 2000 Mar 3;287(5458):1603-4 - PubMed
  21. N Engl J Med. 2002 Feb 21;346(8):557-63 - PubMed
  22. N Engl J Med. 2002 Feb 21;346(8):549-56 - PubMed
  23. Am J Clin Oncol. 1998 Aug;21(4):355-61 - PubMed
  24. Int J Hyperthermia. 1997 Mar-Apr;13(2):141-7 - PubMed
  25. Semin Radiat Oncol. 2011 Apr;21(2):101-10 - PubMed
  26. Radiat Res. 1997 May;147(5):541-50 - PubMed
  27. Cancer Res. 2001 Apr 1;61(7):3027-32 - PubMed

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