Purpose: To address confounding issues that have been noted in planning and conducting studies to identify biomarkers of radiation injury, develop animal models to simulate these injuries, and test potential medical countermeasures to mitigate/treat damage caused by radiation exposure. Methods: The authors completed an intensive literature search to address several key areas that should be considered before embarking on studies to assess efficacy of medical countermeasure approaches in mouse models of radiation injury. These considerations include: 1) study variables; 2) animal selection criteria; 3) animal husbandry; 4) medical management; and 5) radiation attributes. Results: It is important to select mouse strains that are capable of responding to the selected radiation exposure (e.g., genetic predispositions might influence radiation sensitivity and proclivity to certain phenotypes of radiation injury), and that also react in a manner similar to humans. Gender, vendor, age, weight, and even seasonal variations are all important factors to consider. In addition, the housing and husbandry of the animals (i.e. feed, environment, handling, time of day of irradiation and animal restraint), as well as the medical management provided (e.g., use of acidified water, antibiotics, routes of administration of drugs, consideration of animal numbers, and euthanasia criteria) should all be addressed. Finally, the radiation exposure itself should be tightly controlled, by ensuring a full understanding and reporting of the radiation source, dose and dose rate, shielding and geometry of exposure, while also providing accurate dosimetry. It is important to understand how all the above factors contribute to the development of radiation dose response curves for a given animal facility with a well-defined murine model. Conclusions: Many potential confounders that could impact the outcomes of studies to assess efficacy of a medical countermeasure for radiation-induced injuries are addressed, and recommendations are made to assist investigators in carrying out research that is robust, reproducible, and accurate.

目的：解决规划和进行研究以确定放射损伤的生物标记物时注意到的混杂问题，开发模拟这些损伤的动物模型，并测试潜在的医学对策以减轻/治疗由辐射暴露引起的损害。方法：作者完成了广泛的文献搜索，以解决在着手评估医学对策方法在放射损伤小鼠模型中的疗效之前应考虑的几个关键领域。这些考虑因素包括：1）研究变量；2）动物选择标准；3）畜牧业；4）医疗管理；5）辐射属性。结果：重要的是要选择能够对选定的辐射暴露做出反应的小鼠品系（例如，遗传易感性可能会影响辐射敏感性和对某些辐射损伤表型的易感性），并且它们也会以类似于人类的方式发生反应。性别，供应商，年龄，体重，甚至季节性变化都是要考虑的重要因素。此外，动物的住房和饲养（即饲料，环境，处理，一天中的辐照时间和动物约束）以及提供的医疗管理（例如，使用酸化水，抗生素，给药途径） ，考虑动物数量和安乐死标准）。最后，应严格控制辐射暴露本身，通过确保对辐射源，剂量和剂量率，辐射的屏蔽和几何形状有充分的了解和报告，同时还提供准确的剂量测定。重要的是要了解上述所有因素如何对具有明确定义的小鼠模型的给定动物设施的辐射剂量响应曲线的发展做出贡献。结论：解决了许多可能影响研究结果以评估针对辐射引起的伤害的医学对策的有效性的混杂因素，并提出了一些建议，以协助研究人员进行可靠，可重复和准确的研究。