Abstract

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.

中文翻译：

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研究可能影响辐射损伤小鼠模型中医学对策功效测试的后勤工作

摘要

目的

为了解决在规划和开展研究以识别辐射损伤的生物标志物时注意到的混淆问题，开发动物模型来模拟这些损伤，并测试潜在的医学对策以减轻/治疗辐射暴露造成的损害。

方法

作者完成了深入的文献检索，以解决在开始研究评估医学对策方法在辐射损伤小鼠模型中的功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；（四）医疗管理；(5)辐射属性。

结果

重要的是选择能够对选定的辐射暴露作出反应（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倾向）并且以与人类相似的方式作出反应的小鼠品系。性别、供应商、年龄、体重，甚至季节性变化都是需要考虑的重要因素。此外，动物的饲养和饲养（即饲料、环境、处理、一天中的照射时间和动物约束）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）都应该得到解决。最后，辐射暴露本身应该被严格控制，通过确保全面了解和报告辐射源、剂量和剂量率、屏蔽和暴露几何形状，同时提供准确的剂量测定。重要的是要了解所有上述因素如何促成具有明确定义的小鼠模型的给定动物设施的辐射剂量反应曲线的发展。

结论

解决了许多可能影响研究结果的潜在混杂因素，这些混杂因素可能会影响评估医疗对策对辐射引起的伤害的疗效，并提出建议以帮助研究人员开展稳健、可重复和准确的研究。