The rasH2 Mouse Model for Assessing Carcinogenic Potential of Pharmaceuticals
| Autor: | Daniel Morton, Prashant R. Nambiar |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Indoles Carcinogenicity Tests Uterus Physiology Mice Transgenic Spleen Toxicology Pathology and Forensic Medicine Bazedoxifene Rats Sprague-Dawley Mice Internal medicine Sunitinib medicine Carcinoma Chronic Progressive Nephropathy Animals Pyrroles Molecular Biology Carcinogen Cell Proliferation business.industry Body Weight Neoplasms Experimental Cell Biology medicine.disease Rats Genes ras medicine.anatomical_structure Hemangiosarcoma Endocrinology Models Animal Female business medicine.drug |
| Zdroj: | Toxicologic Pathology. 41:1058-1067 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623313477257 |
| Popis: | A factor limiting widespread use of the transgenic rasH2 mouse model for carcinogenicity testing of pharmaceuticals is the paucity of published data on actual drug candidates in rasH2 mice. This report addresses this gap by highlighting rasH2 mouse study data for 10 pharmaceutical candidates. These results were compared with findings in the 2-year studies in Sprague-Dawley rats for the same 10 compounds. In the 6-month rasH2 studies, only 2 of the 10 compounds tested positive for carcinogenicity and these correlated with positive findings in the companion 2-year rat studies. One compound, sunitinib, produced gastroduodenal carcinoma in both sexes and increased hemangiosarcoma in spleen and uterus in female rasH2 mice; in rats it produced gastroduodenal carcinoma and increased pheochromocytoma (males only). The second compound, bazedoxifene, produced ovarian granulosa cell neoplasms in rasH2 mice and rats, and renal tubular neoplasms associated with increased chronic progressive nephropathy only in rats. The higher percentage of carcinogenicity positive rat bioassays could be attributed to rat-specific phenomena with little or low relevance to man. Thus, this article confirms previous reports that rasH2 mice develop rodent-specific neoplasms less frequently than rats and positive findings, when present, are accompanied by similar positive results in the rat. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|