Radiation-induced damage to mouse urothelial barrier.

Abstract

To determine changes of the urothelial barrier during the early as well as late radiation response in mouse urinary bladder. Groups of mice were irradiated with a single dose of 20Gy and sacrificed between days 0 and 360. Urothelial cell numbers were counted, and the fraction of urothelium with a positive immunohistochemical signal for uroplakin-III (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). 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). 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.