Radiation-induced damage to mouse urothelial barrier

Purpose: To determine changes of the urothelial barrier during the early as well as late radiation response in mouse urinary bladder. Materials and methods: Groups of mice were irradiated with a single dose of 20 Gy and sacrificed between days 0 and 360. Urothelial cell numbers were counted, and the fraction of urothelium with a positive immunohistochemical signal for uroplakin-Ill (UP-III) on the luminal surface of the bladder was defined. Also, cytoplasmic UP-III staining signal in urothelium was quantified using an arbitrary score (0-3). Results: Irradiation resulted in a significant decrease in the number of superficial umbrella cells during the early response phase (days 0-31) as well as during the initial late radiation reaction (days 90, 120). Progressive loss of the UP-III layer on the bladder luminal surface correlated with the decrease in the number of umbrella cells (p = 0.002). Also, increased cytoplasmic staining of UP-III in the urothelium was seen after irradiation, correlating negatively with the reduction of the superficial UP-III layer (p < 0.0001). Conclusion: Irradiation of the urinary bladder results in morphological impairment of the urothelial barrier that is associated with a loss of superficial umbrella cells during the early as well as initial late radiation response phase. (c) 2006 Elsevier Ireland Ltd. All rights reserved.