OBJECTIVES: Carcinogen-induced bladder cancer in rodents is a key model for evaluation of novel therapies for bladder cancer because of its similarity to the clinical disease. The major drawback of the model is the difficulty in assessing tumor burden in living animals and at necropsy. The objective of this work was to present simple and accurate solutions for this problem. METHODS: Sixty female Wistar rats were given N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) at a concentration of 0.05% in the drinking water for 35 weeks. Periodic evaluation of tumorigenesis was done by ultrasonography of the anesthetized animals. The tumor burden was evaluated after killing the rats by weighing the bladder, digital measurement of the tumor dimensions, and histologic examination. RESULTS: Focal urothelial hyperplasia was noted by the 5th BBN week, severe dysplasia by the 15th BBN week, and transitional cell carcinoma from the 20th week on. Carcinoma was seen on digital photographs taken from the 20th week on. Tumors as small as 1 mm could be easily measured. A poor correlation (R2 = 0.33) was found between bladder weight and the digital photographic measurements of small tumors (20th BBN week). However, when larger tumors were considered (30th BBN week), a good correlation was found (R2 = 0.81). CONCLUSIONS: Tumor progress in the rat BBN model was accurately monitored by ultrasonography in living animals. Digital measurement of tumor dimensions provided a precise method for evaluation of tumor burden at necropsy.
OBJECTIVES: Carcinogen-induced bladder cancer in rodents is a key model for evaluation of novel therapies for bladder cancer because of its similarity to the clinical disease. The major drawback of the model is the difficulty in assessing tumor burden in living animals and at necropsy. The objective of this work was to present simple and accurate solutions for this problem. METHODS: Sixty female Wistar rats were given N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) at a concentration of 0.05% in the drinking water for 35 weeks. Periodic evaluation of tumorigenesis was done by ultrasonography of the anesthetized animals. The tumor burden was evaluated after killing the rats by weighing the bladder, digital measurement of the tumor dimensions, and histologic examination. RESULTS: Focal urothelial hyperplasia was noted by the 5th BBN week, severe dysplasia by the 15th BBN week, and transitional cell carcinoma from the 20th week on. Carcinoma was seen on digital photographs taken from the 20th week on. Tumors as small as 1 mm could be easily measured. A poor correlation (R2 = 0.33) was found between bladder weight and the digital photographic measurements of small tumors (20th BBN week). However, when larger tumors were considered (30th BBN week), a good correlation was found (R2 = 0.81). CONCLUSIONS:Tumor progress in the ratBBN model was accurately monitored by ultrasonography in living animals. Digital measurement of tumor dimensions provided a precise method for evaluation of tumor burden at necropsy.
Authors: João C Fernandes; José Sereno; Patricia Garrido; Belmiro Parada; Maria F X Cunha; Flávio Reis; Manuela E Pintado; Alice Santos-Silva Journal: Mar Drugs Date: 2012-12 Impact factor: 5.118