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.
Highlights
Oxygen is of vital importance in radiotherapy response [1]
The oxygen effect is most commonly explained attribution to the by the oxygen fixation hypothesis, which postulates that radical-induced DNA damage can be author(s) and the title of the work, journal citation permanently ‘fixed’ by molecular oxygen, rendering DNA damage irreparable
Experiments performed in cells, yeast and bacteria conform to the same general oxygen enhancement ratio (OER) curve, which rises and quickly saturates [1], obeying a roughly hyperbolic relationship with oxygen tension [1, 7, 8]
Summary
The presence of oxygen in tumours has substantial impact on treatment outcome; relative to anoxic licence. The oxygen effect is most commonly explained attribution to the by the oxygen fixation hypothesis, which postulates that radical-induced DNA damage can be author(s) and the title of the work, journal citation permanently ‘fixed’ by molecular oxygen, rendering DNA damage irreparable. 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 reveals a small thermal dependency exists but that this is unlikely to be exploitable
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
