Department of Mathematics, University of California at Berkeley, Berkeley, California.
Department of Mathematics and Statistics, Idaho State University, Pocatello, Idaho.
Radiat Res. 2023 Sep 1;200(3):232-241. doi: 10.1667/RADE-22-00189.1.
In radiobiology, and throughout translational biology, synergy theories for multi-component agent mixtures use 1-agent dose-effect relations (DERs) to calculate baseline neither synergy nor antagonism mixture DERs. The most used synergy theory, simple effect additivity, is not self-consistent when curvilinear 1-agent DERs are involved, and many alternatives have been suggested. In this paper we present the mathematical aspects of a new alternative, generalized Loewe additivity (GLA). To the best of our knowledge, generalized Loewe additivity is the only synergy theory that can systematically handle mixtures of agents that are malstressors (tend to produce disease) with countermeasures - agents that oppose malstressors and ameliorate malstressor damage. In practice countermeasures are often very important, so generalized Loewe additivity is potentially far-reaching. Our paper is a proof-of-principle preliminary study. Unfortunately, generalized Loewe additivity's scope is restricted, in various unwelcome but perhaps unavoidable ways. Our results illustrate its strengths and its weaknesses. One area where our methodology has potentially important applications is analyzing counter-measure mitigation of galactic cosmic ray damage to astronauts during interplanetary travel.
在放射生物学和整个转化生物学中，多成分药物混合物的协同作用理论使用单药剂量效应关系（DER）来计算基线协同作用或拮抗作用混合物 DER。最常用的协同作用理论——简单效应加性，在涉及曲线 1 药 DER 时是不一致的，因此已经提出了许多替代理论。在本文中，我们介绍了一种新的替代理论——广义 Loewe 加性（GLA）的数学方面。据我们所知，广义 Loewe 加性是唯一一种能够系统处理药物混合物的协同作用理论，这些药物混合物既是应激源（倾向于产生疾病），又是对抗应激源并减轻应激源损伤的对策。在实践中，对策通常非常重要，因此广义 Loewe 加性具有潜在的深远意义。我们的论文是一项初步的原理验证研究。不幸的是，广义 Loewe 加性的范围受到限制，以各种不受欢迎但可能不可避免的方式。我们的结果说明了它的优势和劣势。我们的方法可能具有重要应用的一个领域是分析在星际旅行中对抗宇宙射线对宇航员的损害的对策缓解。
