title: Vacuolation in renal tubular epithelium of Cd-1 mice: an incidental finding.
abstract: Prominent cytoplasmic vacuoles were observed in renal tubular epithelial cells of the outer medulla in several kidneys from test article-dosed mice (Crl:CD-1 (ICR)BR VAF/PLUS) during routine light microscopic (LM) examination. Because the vacuolar change was detected infrequently and was not found in any control mice from that study, it was not clear whether the vacuolation represented a drug-induced change. To address this question, kidney sections from mice from multiple unrelated studies were examined by LM for similar vacuolar changes. Vacuolation was seen by LM in 2.3% of the control and 2.8% of the test article-dosed mice. Transmission electron microscopy (TEM) was also performed on kidneys with prominent light microscopic vacuoles in 5 control mice and 2 test article-dosed mice to further characterize the vacuoles. Ultrastructurally, the vacuoles contained fibrillar and finely stipled granular material or membranous whorls. Kidneys from control mice lacking light microscopic evidence of vacuolation had smaller vacuoles containing similar material when examined by TEM. Because vacuoles were present in both control mice and test article-dosed mice, it was concluded that the vacuoles were incidental and unrelated to compound administration. These studies also demonstrated that vacuoles can be expected to be observed by LM examination in 2-3% of Crl:CD-1 (ICR)BR VAF/PLUS, mice.
authors.affiliation: Schering-Plough Research Institute, Lafayette, New Jersey 07848, USA. Robert.Johnson@spri.com
authors.forename: R C
authors.initials: RC
authors.lastname: Johnson
authors.forename: B J
authors.initials: BJ
authors.lastname: Dovey-Hartman
authors.forename: J
authors.initials: J
authors.lastname: Syed
authors.forename: M W
authors.initials: MW
authors.lastname: Leach
authors.forename: D W
authors.initials: DW
authors.lastname: Frank
authors.forename: D P
authors.initials: DP
authors.lastname: Sinha
authors.forename: E J
authors.initials: EJ
authors.lastname: Mirro
authors.forename: J M
authors.initials: JM
authors.lastname: Little
authors.forename: W H
authors.initials: WH
authors.lastname: Halliwell
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000201:enzymology / Q000648:ultrastructure*; D005260:Female; D007124:Immunoenzyme Techniques; D007425:Intracellular Membranes / Q000201:enzymology / Q000648:ultrastructure; D007679:Kidney Medulla / Q000201:enzymology / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000201:enzymology / Q000648:ultrastructure*; D008247:Lysosomes / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D009113:Muramidase / Q000032:analysis; D010503:Periodic Acid-Schiff Reaction; D014617:Vacuoles / Q000201:enzymology / Q000648:ultrastructure*
chemical_list: D009113:Muramidase