Gastric neuroendocrine tumors in a 2-year oncogenicity study with CD-1 mice.
Descriptions of two rare gastric neuroendocrine tumors (carcinoids) of enterochromaffin (ECL) cells in CD-1 mice (2/50) from a 104-week oncogenicity study of a serotonergic/dopaminergic compound are presented. These tumors were detected at necropsy and confirmed by histopathology in hematoxylin and eosin- and Chromogranin A-stained slides. ECL cell counts of the glandular stomachs were determined by quantitative image analysis and did not reveal any hyperplastic changes as possible predisposing lesions for carcinoid formation. To investigate the possibility of drug-induced hypergastrinemia as the cause of tumor formation of ECL cells, gastrin blood levels were measured after treating mice for 7 days with the test substance. In this study, Omeprazole, the positive control, raised gastrin levels, while the test material did not. It was concluded that these two tumors were an example of "late-life"-occurring, spontaneous neuroendocrine tumors in the stomachs of aged CD-1 mice.
Thoolen
Bob
B
Drug Safety Department, Solvay Pharmaceuticals Research Laboratories, Weesp, The Netherlands. bob.thoolen@solvay.com
Koster
Henk
H
van Kolfschoten
Anton
A
de Haan
Martin
M
D000375:Aging; D000818:Animals; D002276:Carcinoid Tumor / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions; D004759:Enterochromaffin Cells / Q000187:drug effects; D005260:Female; D005755:Gastrins / Q000097:blood / Q000187:drug effects; D008297:Male; D051379:Mice; D009853:Omeprazole / Q000494:pharmacology; D012727:Sex Characteristics; D013274:Stomach Neoplasms / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
D053379:Chromogranin A; D002864:Chromogranins; D005755:Gastrins; D009853:Omeprazole