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

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 radioresponse is known as the oxygen enhancement ratio. The oxygen effect ismost commonly explained by the oxygen fixation hypothesis, which postulates that radical-inducedDNAdamage can be permanently ‘fixed’ bymolecular oxygen, renderingDNAdamage irreparable.While this oxygen effect is important in both existing therapy and for futuremodalities such a radiation dose-painting, themajority of existingmathematicalmodels for oxygen enhancement are empirical rather than based on the underlying physics and radiochemistry. Herewe propose amodel of oxygen-enhanced damage fromphysical first principles, investigating factors thatmight influence the cell kill. This isfitted to a range of experimental oxygen curves from literature and shown to describe themwell, yielding a single robust term for oxygen interaction obtained. Themodel also reveals a small thermal dependency exists but that this is unlikely to be exploitable.