Toxicologic Pathology

 

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Toxicologic Pathology, Vol. 30, No. 3, 322-327 (2002)
DOI: 10.1080/01926230252929891

Gastric Neuroendocrine Tumors in a 2-Year Oncogenicity Study With CD-1 Mice

Bob Thoolen

Drug Safety Department, Solvay Pharmaceuticals Research Laboratories, Weesp, The Netherlands, bob.thoolen@ solvay.com

Henk Koster

Drug Safety Department, Solvay Pharmaceuticals Research Laboratories, Weesp, The Netherlands

Anton Van Kolfschoten

Drug Safety Department, Solvay Pharmaceuticals Research Laboratories, Weesp, The Netherlands

Martin De Haan

Drug Safety Department, Solvay Pharmaceuticals Research Laboratories, Weesp, The Netherlands

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 hypergastrinemi a 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.

Key Words: Carcinoids • CD-1 mice • Chromogranin A • ECL cells • gastrin • neuroendocrine tumor • stomach.


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