Incisor Degeneration in Rats Induced by Vascular Endothelial Growth Factor/Fibroblast Growth Factor Receptor Tyrosine Kinase Inhibition
| Autor: | Anthony M. Fletcher, Helen E. Janke, William J. Janusz, Carla L. Bregman, Gene E. Schulze, Theodora W. Salcedo, Jochen Woicke, Robert H. Zidell, Mark G. Mense, Hengsheng Fang |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Angiogenesis Inhibitors Biology Toxicology Fibroblast growth factor Pathology and Forensic Medicine Rats Sprague-Dawley Necrosis chemistry.chemical_compound stomatognathic system Internal medicine Toxicity Tests medicine Dentin Animals Pyrroles Receptor Fibroblast Growth Factor Type 1 Protein Kinase Inhibitors Molecular Biology Dose-Response Relationship Drug Odontoblasts Triazines Enamel organ Cell Biology Vascular Endothelial Growth Factor Receptor-2 Rats Incisor Vascular endothelial growth factor stomatognathic diseases Odontoblast medicine.anatomical_structure Endocrinology chemistry Fibroblast growth factor receptor Pulp (tooth) Female Ameloblast |
| Zdroj: | Toxicologic Pathology. 38:267-279 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623309357950 |
| Popis: | BMS-645737, an inhibitor of vascular endothelial growth factor (VEGF) receptor-2 and fibroblast growth factor (FGF) receptor-1, has anti-angiogenic activity and was evaluated in nonclinical studies as a treatment for cancer. This article characterizes the BMS-645737-induced clinical, gross, and histologic lesions of incisor teeth in Sprague-Dawley (SD) rats. Rats received 0 800 mg/kg BMS-645737 in a single-dose study or consecutive daily doses of 0 20 mg/kg/day in a 1-month study. The reversibility of these effects was assessed in the 1-month study. White discoloration and fracture of incisors were observed clinically and grossly in the 1-month study. In both studies, dose-dependent histopathologic lesions of incisors were degeneration and/or necrosis of odontoblasts and ameloblasts; decreased mineralization of dentin; inflammation and necrosis of the dental pulp; and edema, congestion, and hemorrhage in the pulp and periodontal tissue adjacent to the enamel organ. Partial recovery was observed at lower doses after a two-week dose-free period in the one-month study. Drug-induced incisor lesions were considered to be related to the pharmacologic inhibitory effects on VEGF and FGF signaling, that is, inhibition of growth and maintenance of small-diameter vessels that support the formation of dentin and enamel in growing teeth and/or to perturbances of function of odontoblasts and ameloblasts or their precursors. |
| Databáze: | OpenAIRE |
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