Late functional response of mouse urinary bladder to fractionated X-irradiation

Late functional changes in mouse urinary bladder were studied after fractionated irradiation in order to define parameters of repair of sublethal radiation damage.

In the repair capacity study, 1 to 10 fractions were applied within 5 days. To assess the kinetics of repair, 4 fractions were applied with intervals of 0, 0.5, 1, 2, 4, or 8h. The endpoint used to establish dose-effect relationships was a reduction in the cystometrically measured bladder capacity by > or = 50% of the individual pre-treatment value. Data analysis was performed with a linear-quadratic mixture model, which includes latent-time analysis in an effect-dependent manner.

The alpha/beta values were found to be 4.4 Gy (95% confidence interval [2.0-8.4]) for the repair capacity data alone and 3.7 Gy (1.7-6.7) in combination with the repair kinetics data. The half-time of repair, assuming mono-exponential repair kinetics, was 0.39 h (95% CI [0.23-1.3]). The mean latent time decreased from around 40 weeks to 12 weeks, inversely dependent on the biologically effective dose. In animals experiencing an acute response during the first month after treatment, the incidence of severe late responses was significantly increased (p=0.0025).

The present results confirm that the sparing effect in the mouse urinary bladder by dose fractionation is in the lower range of chronically responding tissues. The half-time of repair is in the lower range reported for mouse tissues.