title: Common handling procedures conducted in preclinical safety studies result in minimal hepatic gene expression changes in Sprague-Dawley rats.
abstract: Gene expression profiling is 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 baseline gene expression. We report gene expression changes in the livers of female Sprague-Dawley rats following common handling procedures. Baseline gene expression changes identified in this study provide insight on how these changes may affect interpretation of gene expression profiles following compound exposure. Rats were divided into three groups. One group was not subjected to handling procedures 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. 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.
authors.affiliation: Comparative Biology and Safety Sciences, Amgen Inc., Seattle, Washington, United States of America.
authors.forename: Yudong D
authors.initials: YD
authors.lastname: He
authors.affiliation: Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, California, United States of America.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Karbowski
authors.affiliation: Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, California, United States of America.
authors.forename: Jon
authors.initials: J
authors.lastname: Werner
authors.affiliation: Comparative Biology and Safety Sciences, Amgen Inc., Seattle, Washington, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Everds
authors.affiliation: Comparative Biology and Safety Sciences, Amgen Inc., Seattle, Washington, United States of America.
authors.forename: Chris
authors.initials: C
authors.lastname: Di Palma
authors.affiliation: Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, California, United States of America.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, California, United States of America.
authors.forename: Marnie
authors.initials: M
authors.lastname: Higgins-Garn
authors.affiliation: Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, California, United States of America.
authors.forename: Sandra
authors.initials: S
authors.lastname: Tran
authors.affiliation: Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, California, United States of America.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Afshari
authors.affiliation: Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, California, United States of America.
authors.forename: Hisham K
authors.initials: HK
authors.lastname: Hamadeh
mesh_terms: D032761:Animal Experimentation; D000818:Animals; D016477:Artifacts; D001800:Blood Specimen Collection / Q000662:veterinary; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D008099:Liver / Q000378:metabolism*; D008957:Models, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000662:veterinary; D015398:Signal Transduction / Q000235:genetics