Simulating galactic cosmic ray effects: Synergy modeling of murine tumor prevalence after exposure to two one-ion beams in rapid sequence
Simulating galactic cosmic ray effects: Synergy modeling of murine tumor prevalence after exposure to two one-ion beams in rapid sequence
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DOI：
10.1016/j.lssr.2020.01.001
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发表时间：
2020-05-01
影响因子：
2.5
通讯作者：
Sachs, Rainer K.
中科院分区：
文献类型：
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作者：
Huang, Edward Greg;Wang, Ren-Yi;Sachs, Rainer K.
低地球轨道以上空间旅行中银河宇宙射线（GCR）的健康风险仍然令人担忧。多年来，研究空间辐射诱导的小鼠哈氏腺（HG）肿瘤发生率的加速器实验一直在进行，以帮助估计GCR风险。大多数研究使用急性、相对低通量的暴露。单个离子和线性能量转移（LET）的广泛光谱的结果已经成为可用。然而，在太空中，机组人员同时暴露于许多不同的GCR。美国宇航局布鲁克海文空间辐射实验室（NSRL）最近的升级现在允许以不同的单离子束的形式以快速顺序提供混合物。本文使用三个两离子混合物实验的结果来说明概念，数学，计算和统计方面的协同分析，也作为一个临时报告的混合物实验的结果。使用以下内容解释结果：（a）来自HG单离子加速器实验的累积数据;（B）增量效应加和性协同理论，而不是简单效应加和性协同理论;（c）单离子剂量效应关系的简约模型;以及（d）封装在可免费获得的开源定制软件中的计算机实现的数值方法。主要结论如下。到目前为止，鼠HG肿瘤发生实验研究仅在三分之一的情况下显示协同作用。此外，一些理论论证表明GCR模拟混合光束不太可能是协同的。然而，正在研究各种终点的各种团体需要进行更多与可能的协同作用有关的研究。尤其重要的是高LET辐射之间协同作用的可能性，因为单个高LET离子对许多终点具有较大的相对生物学效应。DER -剂量-效应关系;单离子束的E（d）- DER，其中d是剂量; HG患病率p -在本文中，p是具有至少一个哈氏腺肿瘤的小鼠的数量除以处于发展哈氏腺肿瘤风险的小鼠的数量（因此，在本文中，从概念上讲，流行率p永远不会大于1）; IEA -增量效应加和协同理论;协同水平-在图5中举例说明的观察到的协同作用有多明确的说明;混合原则-协同理论上的一致性条件，其确保协同理论以数学上自洽的方式处理试剂混合物的混合物; NTE -非靶向效应; NSNA -既不协同也不拮抗; SEA -简单效应加和协同理论; TE -靶向效应; β * -相对于光速的离子速度，其中0 <β * < 1; SLI -快速轻离子。
Health risks from galactic cosmic rays (GCR) in space travel above low earth orbit remain a concern. For many years accelerator experiments investigating space radiation induced prevalence of murine Harderian gland (HG) tumorigenesis have been performed to help estimate GCR risks. Most studies used acute, relatively low fluence, exposures. Results on a broad spectrum of individual ions and linear energy transfers (LETs) have become available. However, in space, the crew are exposed simultaneously to many different GCR. Recent upgrades at the Brookhaven NASA Space Radiation Laboratory (NSRL) now allow mixtures in the form of different one-ion beams delivered in rapid sequence. This paper uses the results of three two-ion mixture experiments to illustrate conceptual, mathematical, computational, and statistical aspects of synergy analyses and also acts as an interim report on the mixture experiments' results. The results were interpreted using the following: (a) accumulated data from HG one-ion accelerator experiments; (b) incremental effect additivity synergy theory rather than simple effect additivity synergy theory; (c) parsimonious models for one-ion dose-effect relations; and (d), computer-implemented numerical methods encapsulated in freely available open source customized software. The main conclusions are the following. As yet, the murine HG tumorigenesis experimental studies show synergy in only one case out of three. Moreover, some theoretical arguments suggest GCR-simulating mixed beams are not likely to be synergistic. However, more studies relevant to possible synergy are needed by various groups that are studying various endpoints. Especially important is the possibility of synergy among high-LET radiations, since individual high-LET ions have large relative biological effectiveness for many endpoints.Selected terminology, symbols, and abbreviations. DER - dose-effect relation; E(d) - DER of a one-ion beam, where d is dose; HG prevalence p - in this paper, p is the number of mice with at least one Harderian gland tumor divided by the number of mice that are at risk of developing Harderian gland tumors (so that in this paper prevalence p can never, conceptually speaking, be greater than 1); IEA - incremental effect additivity synergy theory; synergy level - a specification, exemplified in Fig. 5, of how clear-cut an observed synergy is; mixmix principle - a consistency condition on a synergy theory which insures that the synergy theory treats mixtures of agent mixtures in a mathematically self-consistent way; NTE - non-targeted effect(s); NSNA - neither synergy nor antagonism; SEA - simple effect additivity synergy theory; TE - targeted effect(s); beta* - ion speed relative to the speed of light, with 0 < beta* < 1; SLI - swift light ion(s).