Consumer and Clinical Radiation Protection Bureau, Health Canada, Ottawa, ON, Canada.
US Department of Energy, Germantown, MD, USA.
Int J Radiat Biol. 2021;97(1):60-67. doi: 10.1080/09553002.2020.1761570. Epub 2020 May 13.
A large body of radiobiological data has been generated over the past century using in vitro, animal and epidemiological models. This information represents global efforts to understand the mechanistic basis of radiation-induced health effects. However, it has been difficult to effectively integrate this data to derive meaningful information for refining the guidance on chronic, low dose radiation exposure for workers and the public.
To increase our understanding of radiation risks and the biological processes that contribute to those risks, a paradigm shift is needed that will enable integration of information across levels of biological organization from a 'stressor' centric to an 'adverse outcome' approach to risk assessment. In chemical and ecological toxicity, a framework has been developed that captures available biologically-based knowledge in the literature and links it to outcomes of relevance to chemical toxicity, resulting in an adverse outcome pathway (AOP).
In this paper, we discuss the AOP concept, how it can be applied to the radiation field, and our vision for the next steps. For the approach to be successful, the radiation research community will need to work collaboratively to vet the vast amount of literature and harness the data in a systematic manner for incorporation into a framework based on the AOP approach.
We anticipate that AOPs could be adopted as a method to synthesize current available information to facilitate the identification of knowledge gaps, better co-ordinate research and qualitatively and quantitatively link key events to an adverse outcome. This can further assist in identifying biomarkers relevant to radiation exposures, refining risk from co-exposures and understanding critical events at the molecular, cellular, tissue, organ and whole animal level related to low dose/dose-rate exposures.
在过去的一个世纪中，通过体外、动物和流行病学模型已经产生了大量的放射生物学数据。这些信息代表了全球努力理解辐射诱导健康效应的机制基础。然而，很难有效地整合这些数据，以从中得出对完善有关工人和公众慢性低剂量辐射暴露的指导的有意义的信息。
为了增进我们对辐射风险以及导致这些风险的生物学过程的理解，需要进行范式转变，使我们能够将信息从以“应激源”为中心整合到以“不良后果”为中心的风险评估方法，从而跨生物组织层次整合信息。在化学和生态毒性领域，已经开发了一种框架，该框架可以捕获文献中可用的基于生物学的知识，并将其与与化学毒性相关的结果联系起来，从而形成不良后果途径（AOP）。
在本文中，我们讨论了 AOP 概念，它如何应用于辐射领域，以及我们对下一步的设想。为了使该方法取得成功，辐射研究界需要协作审查大量文献，并以系统的方式利用这些数据，将其纳入基于 AOP 方法的框架中。
我们预计 AOP 可以被采用为一种综合当前可用信息的方法，以促进确定知识差距，更好地协调研究，并定性和定量地将关键事件与不良后果联系起来。这可以进一步有助于确定与辐射暴露相关的生物标志物，完善共同暴露的风险，并理解与低剂量/剂量率暴露相关的分子、细胞、组织、器官和整体动物水平的关键事件。
