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Gastric neuroendocrine tumors in a 2-year oncogenicity study with CD-1 mice
Bob Thoolen1, Henk Koster, Anton van Kolfschoten
1Drug Safety Department, Solvay Pharmaceuticals Research Laboratories, Weesp, The Netherlands. bob.thoolen@solvay.com
Abstract:
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.
Insights
Two rare gastric neuroendocrine tumors (carcinoids) were found in aged mice. The study concluded these were spontaneous, not drug-induced, tumors in aged CD-1 mice.
Area of Science:
- Toxicology
- Oncology
- Gastroenterology
Background:
- Neuroendocrine tumors, specifically enterochromaffin (ECL) cell carcinoids, are rare gastric neoplasms.
- Assessing potential drug-induced tumorigenesis requires careful evaluation of spontaneous tumor incidence.
Purpose of the Study:
- To describe two rare gastric neuroendocrine tumors (carcinoids) observed in a long-term mouse study.
- To investigate the potential link between a serotonergic/dopaminergic compound and tumor formation in enterochromaffin (ECL) cells.
Main Methods:
- Histopathological examination of gastric tissues from CD-1 mice after a 104-week oncogenicity study.
- Quantitative image analysis for ECL cell counts and assessment of hyperplastic changes.
- Measurement of gastrin blood levels following short-term drug administration to evaluate hypergastrinemia.
Main Results:
- Two gastric carcinoids (enterochromaffin cell tumors) were identified in 2 out of 50 CD-1 mice.
- No hyperplastic changes were observed in ECL cells, suggesting no predisposing lesion.
- The test compound did not elevate gastrin levels, unlike the positive control Omeprazole.
Conclusions:
- The observed gastric neuroendocrine tumors are considered spontaneous, late-life occurrences in aged CD-1 mice.
- The study did not find evidence to support drug-induced hypergastrinemia as a cause for these specific tumors.
- These findings contribute to understanding the background incidence of neuroendocrine tumors in aged rodent models.