Common Handling Procedures Conducted in Preclinical Safety Studies Results in Minimal Hepatic Gene Expression Changes in Sprague-Dawley Rats

Gene expression profiling has been used as a tool to gain mechanistic understanding of adverse effects in response to compound exposure. However, little is known about how the common handling procedures of experimental animals during a preclinical study alter their baseline gene expression. We report on gene expression changes in the livers of female Sprague-Dawley rats following common handling procedures. Insight on baseline gene expression changes obtained in this study will allow us to evaluate how these changes may affect interpretation of gene expression profiles following compound exposure. Rats were divided into three groups (n = 10 per group): one group was not subjected to handling procedures, euthanized on day 2, and served as controls for both handled groups. Animals in the other two groups were weighed, subjected to restraint in Broome restrainers, and administered water via oral gavage daily for 1 or 4 days with tail vein blood collections at 1, 2, 4, and 8 hours postdose on days 1 and 4 followed by euthanasia on day 2 or 5. Significantly altered genes were identified in livers of animals following 1 or 4 days of handling when compared to the unhandled animals. Gene changes in animals handled for 4 days were similar to those handled for 1 day, suggesting a lack of habituation. The altered genes were primarily immune function related genes. These findings, along with a correlating increase in corticosterone levels suggest that common handling procedures may cause a minor immune system perturbance. Female Sprague Dawley rats were divided into three groups (n = 10 per group) based on body weights. The control group was not subjected to handling procedures. Animals in the other two groups were weighed, restrained with Broome restrainers which consisted of removing the animal from their home cage, recording body weight, restraining for dose administration and then returning the animal to its home cage. Dose administration consisted of water via oral gavage daily for 1 day or 4 days with tail vein blood collections at 1, 2, 4, and 8 hours postdose on days 1 or 4.