title: A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio.
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.
authors.affiliation: 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.
authors.forename: David Robert
authors.initials: DR
authors.lastname: Grimes
authors.affiliation: 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.
authors.forename: Mike
authors.initials: M
authors.lastname: Partridge
keywords: oxygen; oxygen effect; radiation damage; radiotherapy