Study logistics that can impact medical countermeasure efficacy testing in mouse models of radiation injury.

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.