Radiation-induced impairment of urinary bladder function in mice: fine structure of the acute response and consequences on late effects

Abstract

The time course and dose response of radiation-induced impairment of urinary bladder function in the mouse were assessed after local irradiation with graded single doses. Bladder capacity was defined by transurethral cystometry; a reduction in bladder volume at an intravesical pressure of 10 mmHg by > or =50% of the individual pretreatment control value was considered a positive radiation reaction. Reversible effects of radiation on the urinary bladder were found during the first 30 days postirradiation, followed by a symptom-free latent period and irreversible late changes. Maximum-likelihood analysis revealed that the acute response is composed of two distinct waves from days 1-15 and days 16-30, with mean latent times of 7.1 days [95% confidence interval (5.4, 9.0)] and 23.3 days (21.9, 24.5), respectively, which describe the data significantly better than a single normal distribution (P = 0.0052). The ED50 values (+/- their standard deviation sigma), i.e. the doses at which 50% of the irradiated animals show the > or = 50% reduction in bladder capacity during each of the two intervals, were 21.7 +/- 4.1 and 19.3 +/- 3.9 Gy for the first and the second acute wave, respectively. The ED50 for the late functional effects was 18.7 +/- 2.4 Gy. Multivariate analysis demonstrated (1) that a response during the first acute wave correlated significantly with a reaction in the second acute wave (P = 0.0066), and (2) that a response during the second but not the first acute wave correlated significantly with the development of a late response (P = 0.0008). In conclusion, the present analysis suggests that the radiation response of the urinary bladder of the mouse displays a significant consequential component. However, further studies are required to demonstrate if the frequency of late sequelae can be decreased by an early intervention in the sequence of pathogenic processes.