Abstract

Background

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.

Methods

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).

Results

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.

Conclusion

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.

中文翻译：

---

将不良结果途径框架与辐射风险评估相结合。

摘要

背景

在过去的一个世纪里，使用体外、动物和流行病学模型产生了大量的放射生物学数据。该信息代表了全球为了解辐射引起的健康影响的机制基础所做的努力。然而，很难有效地整合这些数据以获得有意义的信息，以完善有关工人和公众慢性、低剂量辐射照射的指导。

方法

为了增加我们对辐射风险和导致这些风险的生物过程的理解，需要进行范式转变，以实现跨生物组织级别的信息整合，从以“压力源”为中心的风险评估方法到“不利结果”方法。在化学和生态毒性方面，已经开发了一个框架，该框架可以获取文献中现有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，从而导致不良结果途径 (AOP)。

结果

在本文中，我们讨论了 AOP 概念、如何将其应用于辐射领域，以及我们对下一步的展望。为使该方法取得成功，辐射研究界将需要合作审查大量文献并以系统的方式利用数据以纳入基于 AOP 方法的框架。

结论

我们预计可以采用 AOP 作为一种方法来综合当前可用的信息，以促进识别知识差距、更好地协调研究以及将关键事件定性和定量地与不利结果联系起来。这可以进一步帮助识别与辐射暴露相关的生物标志物，改善共同暴露的风险并了解与低剂量/剂量率暴露相关的分子、细胞、组织、器官和整个动物水平的关键事件。