RESUMO
The purpose of this study was to establish a 2-stage model of urinary bladder carcinogenesis in male Sprague-Dawley rats to identify tumor promoters. In phase 1 of the study, rats ( n = 170) were administered 100 mg/kg of the tumor initiator, N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), twice weekly by oral gavage (po) for a period of 6 weeks. Phase 2 consisted of dividing rats into 4 groups ( n = 40 per group) and administering one of the following for 26 weeks to identify putative tumor promoters: (1) vehicle po, (2) 25 mg/kg/day rosiglitazone po, (3) 5% dietary sodium l-ascorbate, and (4) 3% dietary uracil. Rats were necropsied after 7.5 months, and urinary bladders were evaluated by histopathology. BBN/vehicle treatments induced the development of urothelial hyperplasia (83%) and papillomas (15%) but no transitional cell carcinomas (TCCs). Rosiglitazone increased the incidence and severity of papillomas (93%) and resulted in TCC in 10% of treated rats. Uracil was the most effective tumor promoter in our study and increased the incidence of papillomas (90%) and TCC (74%). Sodium ascorbate decreased the incidence of urothelial hyperplasia (63%) and did not increase the incidence of urothelial papillomas or TCC. These data confirm the capacity of our 2-stage model to identify urinary bladder tumor promoters.
Assuntos
Ácido Ascórbico/toxicidade , Carcinógenos/farmacologia , Carcinoma de Células de Transição/induzido quimicamente , Rosiglitazona/toxicidade , Uracila/toxicidade , Neoplasias da Bexiga Urinária/induzido quimicamente , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Bexiga Urinária/efeitos dos fármacosRESUMO
Previously reported cases of congenital cutaneous mast cell tumours in calves were characterized by multiple discrete nodules. The calf presented herein is, to the authors' knowledge, the first documented case of congenital diffuse cutaneous mastocytosis. The entire skin was thickened and wrinkled with particularly prominent skin folds on the head, ventrum, and legs. Histological examination of two haired skin specimens (eyelid, muzzle margin) revealed that the dermis was diffusely infiltrated by sheets of neoplastic mast cells.