Shuryak Igor, Fornace Albert J, Datta Kamal, Suman Shubhankar, Kumar Santosh, Sachs Rainer K, Brenner David J
a Center for Radiological Research, Columbia University, New York, New York.
b Department of Biochemistry and Molecular and Cellular Biology, and Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC; and.
Radiat Res. 2017 Apr;187(4):476-482. doi: 10.1667/RR009CC.1. Epub 2017 Feb 20.
Health risks from space radiations, particularly from densely ionizing radiations, represent an important challenge for long-ranged manned space missions. Reliable methods are needed for scaling low-LET to high-LET radiation risks for humans, based on animal or in vitro studies comparing these radiations. The current standard metric, relative biological effectiveness (RBE) compares iso-effect doses of two radiations. By contrast, a proposed new metric, radiation effects ratio (RER), compares effects of two radiations at the same dose. This definition of RER allows direct scaling of low-LET to high-LET radiation risks in humans at the dose or doses of interest. By contrast to RBE, RER can be used without need for detailed information about dose response shapes for compared radiations. This property of RER allows animal carcinogenesis experiments to be simplified by reducing the number of tested radiation doses. For simple linear dose-effect relationships, RBE = RER. However, for more complex dose-effect relationships, such as those with nontargeted effects at low doses, RER can be lower than RBE. We estimated RBE and RER values and uncertainties using heavy ion (C, Si, Fe) and gamma-ray-induced tumors in a mouse model for intestinal cancer (APC), and used both RBE and RER to estimate low-LET to high-LET risk scaling factors. The data showed clear evidence of nontargeted effects at low doses. In situations, such as the ones discussed here where nontargeted effects dominate at low doses, RER was lower than RBE by factors around 2.8-3.5 at 0.03 Gy and 1.3-1.4 at 0.3 Gy. It follows that low-dose high-LET human cancer risks scaled from low-LET human risks using RBE may be correspondingly overestimated.
太空辐射，尤其是密集电离辐射带来的健康风险，是远程载人太空任务面临的一项重大挑战。需要可靠的方法，基于比较这些辐射的动物或体外研究，将低传能线密度（LET）辐射风险换算为高LET辐射对人类的风险。当前的标准指标，相对生物效应（RBE）比较两种辐射的等效应剂量。相比之下，一种新提出的指标，辐射效应比（RER），比较相同剂量下两种辐射的效应。RER的这一定义使得在感兴趣的一个或多个剂量下，能够直接将低LET辐射风险换算为高LET辐射对人类的风险。与RBE不同，使用RER时无需有关所比较辐射剂量反应曲线形状的详细信息。RER的这一特性可通过减少所测试的辐射剂量数量来简化动物致癌实验。对于简单的线性剂量效应关系，RBE = RER。然而，对于更复杂的剂量效应关系，例如在低剂量下具有非靶向效应的关系，RER可能低于RBE。我们在一种小鼠肠道癌（APC）模型中，利用重离子（碳、硅、铁）和γ射线诱发的肿瘤估算了RBE和RER值及不确定性，并使用RBE和RER二者来估算低LET到高LET的风险换算因子。数据显示出低剂量下存在非靶向效应的明确证据。在此处讨论的低剂量下非靶向效应占主导的情形中，在0.03 Gy时，RER比RBE低约2.8 - 3.5倍，在0.3 Gy时低1.3 - 1.4倍。由此可见，使用RBE从低LET人类风险换算得出的低剂量高LET人类癌症风险可能会相应地被高估。
