| Autor: |
Fletcher AM; Drug Safety Evaluation, Bristol-Myers Squibb Company, Syracuse, New York, NY 13221-4755, USA. anthony.fletcher@bms.com, Bregman CL, Woicke J, Salcedo TW, Zidell RH, Janke HE, Fang H, Janusz WJ, Schulze GE, Mense MG |
| Jazyk: |
angličtina |
| Zdroj: |
Toxicologic pathology [Toxicol Pathol] 2010 Feb; Vol. 38 (2), pp. 267-79. Date of Electronic Publication: 2010 Jan 25. |
| DOI: |
10.1177/0192623309357950 |
| Abstrakt: |
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: |
MEDLINE |
| Externí odkaz: |
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