Office of Air and Radiation, Radiation Protection Division, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.
Institute of Radiation Medicine, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH) Ingolstaedter, Neuherberg, Germany.
Int J Radiat Biol. 2021;97(6):804-814. doi: 10.1080/09553002.2020.1853847. Epub 2020 Dec 16.
The overall aim of this contribution to the 'Second Bill Morgan Memorial Special Issue' is to provide a high-level review of a recent report developed by a Committee for the National Council on Radiation Protection and Measurements (NCRP) titled 'Approaches for Integrating Information from Radiation Biology and Epidemiology to Enhance Low-Dose Health Risk Assessment'. It derives from previous NCRP Reports and Commentaries that provide the case for integrating data from radiation biology studies (available and proposed) with epidemiological studies (also available and proposed) to develop Biologically-Based Dose-Response (BBDR) models. In this review, it is proposed for such models to leverage the adverse outcome pathways (AOP) and key events (KE) approach for better characterizing radiation-induced cancers and circulatory disease (as the example for a noncancer outcome). The review discusses the current state of knowledge of mechanisms of carcinogenesis, with an emphasis on radiation-induced cancers, and a similar discussion for circulatory disease. The types of the various informative BBDR models are presented along with a proposed generalized BBDR model for cancer and a more speculative one for circulatory disease. The way forward is presented in a comprehensive discussion of the research needs to address the goal of enhancing health risk assessment of exposures to low doses of radiation. The use of an AOP/KE approach for developing a mechanistic framework for BBDR models of radiation-induced cancer and circulatory disease is considered to be a viable one based upon current knowledge of the mechanisms of formation of these adverse health outcomes and the available technical capabilities and computational advances. The way forward for enhancing low-dose radiation risk estimates will require there to be a tight integration of epidemiology data and radiation biology information to meet the goals of relevance and sensitivity of the adverse health outcomes required for overall health risk assessment at low doses and dose rates.
本专题贡献的总体目标是对国家辐射防护和测量委员会（NCRP）委员会最近题为“整合辐射生物学和流行病学信息以增强低剂量健康风险评估方法”的报告进行高级别综述。该报告源自 NCRP 之前的报告和评论，为整合来自辐射生物学研究（现有和拟议的）和流行病学研究（也有现有和拟议的）的数据以开发基于生物学的剂量-反应（BBDR）模型提供了依据。在本次综述中，建议此类模型利用不良结局途径（AOP）和关键事件（KE）方法更好地描述辐射诱导癌症和循环系统疾病（作为非癌症结局的示例）。本文讨论了致癌机制的现有知识状况，重点是辐射诱导癌症，以及循环系统疾病的类似讨论。提出了各种信息丰富的 BBDR 模型的类型，并为癌症提出了一个广义的 BBDR 模型，为循环系统疾病提出了一个更具推测性的模型。在综合讨论增强低剂量辐射暴露健康风险评估的研究需求的过程中，提出了前进的方向。考虑到这些不良健康结局形成机制的现有知识以及可用的技术能力和计算进展，将 AOP/KE 方法用于开发辐射诱导癌症和循环系统疾病的 BBDR 模型的机制框架被认为是可行的。要提高低剂量辐射风险估计，需要将流行病学数据和辐射生物学信息紧密结合，以满足对低剂量和剂量率下整体健康风险评估所需的不良健康结局的相关性和敏感性的目标。
