Establishment and diagnosis of N-methyl-N-nitrosourea-induced bladder cancer model in rabbits

Abstract

Objective To construct the rabbit models of orthotopic bladder cancer induced by N-methyl-Nitrosourea (MNU), and to evaluate the value of magnetic resonance imaging (MRI) in the diagnosis of the bladder cancer model. Methods 27 New Zealand white rabbits (weighing 2.5 kg) were randomly divided into experiment group (n=18) and control group (n=9). The experiment group were induced with MNU (10 mg per rabbit) by intravesical administration every other week for for 4 times. Meantime, the control group were treated with normal saline (5 ml per rabbit) by intravesical administration. At the end of the 8th, 10th and 12th week, all rabbits were examined by MRI, then gross observation was performed for the bladder, and the specimens of the bladder were harvested for hematoxylin-eosin staining. Results In experiment group, 17 rabbits were alived during the experiment and 1 rabbits were died at the end of the 6th week. In experimental group at the 8th week, no bladder tumor was detected by MRI and pathologcal examination in 5 rabbits. But some chronic inflammatory cells and fibroblasts were present in the bladder mucosa. At the 10th week, the abnormal signals were found in 5 rabbits by MRI which manifested as local bladder tumor, while 6 rabbits were identified non-muscle-invasive urothelial cell carcinoma by pathology. At the 12th week, abnormal changes were detected in each of the 6 rabbits by MRI scanning and manifested as thickening bladder wall, muscle-invasive urothelial cell carcinoma was diagnosed by pathology in each of rabbits. In control group, 9 rabbits were all alived. There was no abnormal signal in the MRI examination and no bladder cancer in the pathological examination. The tumor response rates of bladder cancer in two groups had significant difference (P<0.05). The accuracy, sensitivity and specificity of MRI in the diagnoses of bladder cancer were 83.3%, 85.7%, 80.0%. Conclusion The methods to establish the rabbit models of orthotopic bladder cancer induced by MNU are simple and reliable; the results of MRI are consistent with the pathological results and MRI examination is a reliable diagnostic method concerning this model. Key words: Bladder cancer; Model, animal; N-methyl-Nitrosourea; Rabbits