A novel model of megavoltage radiation-induced oral mucositis in hamsters: Role of inflammatory cytokines and nitric oxide.

PURPOSE: To design a novel model to study Cobalt-60 (Co-60)-induced radiation mucositis and to describe the pathways involved in its development. MATERIALS AND METHODS: Hamsters' cheeks were treated with Co-60 radiation (10, 20, 30 or 35 Gy). Three days later, oral mucosa scarification was performed with a needle. The animals were euthanized at day 13 (D + 13) after irradiation. Gross and microscopic alterations were evaluated by a new score system that we developed. Also, neutrophil infiltration, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-10, inducible nitric oxide synthase (iNOS), nitric oxide (NO) and nitrite were assessed in oral mucosa. We also tried to establish the roles of TNF-α and IL-1ß and iNOS in our model using pharmacological approaches with pentoxiphylline (PTX) and aminoguanidine (AMG), respectively. RESULTS: We found that a single administration of 35 Gy of Co-60, followed by mechanical scratches 3 days later, induced oral mucositis in hamsters. Animals with mucositis lost weight and had a survival median of 13 days, the time at which peak inflammation occurs. We noticed increased levels of NO, iNOS, TNF-α and IL-1ß and a reduced concentration of IL-10. PTX partially prevented the mucositis phenotype by reducing the levels of inflammatory mediators and iNOS expression. Additionally, AMG, a selective inhibitor of iNOS, reduced Co-60-induced oral mucositis through reducing NO production. CONCLUSION: We described a novel model of megavoltage radiation-induced oral mucositis in hamsters. TNF-α, IL-1ß and NO seem to play a role in the pathophysiology of this model.

Experimental rat lung tumor model with intrabronchial tumor cell implantation.

PURPOSE: The objective of this study was to develop a rat lung tumor model for anticancer drug testing. METHODS: Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. RESULTS: The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. CONCLUSION: The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

Experimental rat lung tumor model with intrabronchial tumor cell implantation

PURPOSE: The objective of this study was to develop a rat lung tumor model for anticancer drug testing. METHODS: Sixty-two female Wistar rats weighing 208 ± 20 g were anesthetized intraperitoneally with 2.5 percent tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5×10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. RESULTS: The tumor take rate was 94.7 percent for implants with 4×10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8 percent. CONCLUSION: The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

OBJETIVO: O objetivo foi desenvolver um modelo de tumor de pulmão em rato que permita o teste de fármacos no tratamento deste câncer. MÉTODOS: Sessenta e dois ratos Wistar fêmeas, peso médio de 208±20 g, foram anestesiados com tribromo-etanol 2,5 por cento IP (1ml/100g de rato), traqueostomizados e intubados com cateter ultrafino para injetar células do tumor de Walker. Na 1ª etapa, estabeleceu-se a técnica do implante de células tumorais por via intrabrônquica e o índice de pega tumoral, usando-se de 10(5) a 5×10(5) células. Na 2ª, avaliou-se o volume tumoral e a correlação dos achados obtidos na tomografia computadorizada de alta resolução (TCAR) de tórax com os da necropsia e verificou-se a sobrevida. RESULTADOS: O índice de pega foi de 94,7, com o implante de 4×10(5) células do tumor; as medidas do tumor feitas na TCAR e comparadas com as da necropsia foram semelhantes (r=0, 953, p<0,0001); a sobrevida mediana foi de 11 dias; e a mortalidade cirúrgica de 4,8 por cento. CONCLUSÃO: O modelo mostrou-se viável, com alto índice de pega, mortalidade cirúrgica desprezível, de execução simples e fácil reprodutibilidade. A TCAR revelou alta acurácia no diagnóstico, localização e mensuração das lesões tumorais, credenciando-se para a monitorização de crescimento tumoral nesse modelo.