A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio. (4th December 2015)

• Record Type: Journal Article
• Authors: Robert Grimes, David; Partridge, Mike
• Is Part Of: Biomedical physics & engineering express. Volume 1:Number 4(2015)
• Publication Date: 2015-12-04
• Subjects: radiotherapy -- oxygen -- oxygen effect -- radiation damage; Medical physics -- Periodicals; Biophysics -- Periodicals; Biomedical engineering -- Periodicals; Medical sciences -- Periodicals; 610.153
• DOI: 10.1088/2057-1976/1/4/045209
• Languages: English
• ISSNs: 2057-1976

Abstract

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.