A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio.
A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio.
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DOI：
10.1088/2057-1976/1/4/045209
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发表时间：
2015-12-04
影响因子：
1.4
通讯作者：
Partridge M
中科院分区：
文献类型：
--
作者：
Grimes DR;Partridge M
肿瘤中氧气的存在对治疗结果有重大影响；相对于缺氧区域，氧合良好的细胞对放疗的反应要好 2.5-3 倍。这种增加的放射反应被称为氧增强比。氧效应最常见的解释是氧固定假说，该假说假设自由基引起的 DNA 损伤可以被分子氧永久“固定”，从而使 DNA 损伤无法修复。虽然这种氧气效应在现有治疗和未来的放射剂量绘制等方式中都很重要，但大多数现有的氧气增强数学模型都是经验性的，而不是基于基础物理和放射化学。在这里，我们根据物理第一原理提出了一个氧增强损伤模型，研究可能影响细胞死亡的因素。这与文献中的一系列实验氧曲线相拟合，并被证明可以很好地描述它们，从而为所获得的氧相互作用产生一个强大的术语。该模型还揭示了存在小的热依赖性，但这不太可能被利用。
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.