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

The time course and dose response of radiation-induced impairment of urinar y bladder function in the mouse were assessed after local irradiation with graded single doses. Bladder capacity was defined by transurethral cystomet ry; a reduction in bladder volume at an intravesical pressure of 10 mmHg by greater than or equal to 50% of the individual pretreatment control value was considered a positive radiation reaction. Reversible effects of radiati on on the urinary bladder were found during the first 30 days postirradiati on, followed by a symptom-free latent period and irreversible late changes. Maximum-likelihood analysis revealed that the acute response Is composed o f 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 devia tion sigma), i.e. the doses at which 50% of the irradiated animals show the greater than or equal to 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 effec ts was 18.7 +/- 2.4 Gy. Multivariate analysis demonstrated (1) that a respo nse 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 sec ond but not the first acute wave correlated significantly with the developm ent of a late response (P = 0.0008). In conclusion, the present analysis su ggests that the radiation response of the urinary bladder of the mouse disp lays a significant consequential component. However, further studies are re quired to demonstrate if the frequency of late sequelae can be decreased by an early intervention in the sequence of pathogenic processes. (C) 1999 by Radiation Research Society.