Long-term recovery and reirradiation tolerance of mouse bladder

The aim of this study was to investigate the influence of overall treatment time on the development and repair of radiation injury in the bladder. The bladders of mice were irradiated with 2 equal doses of X rays separated by 1 day, 3 months or 9 months. Additional groups of mice were given 8 or 16 Gy (approximately 20% and 60%, respectively, of a full tolerance dose) and subsequently reirradiated with a range of test doses after 3 or 9 months. Functional bladder damage was assessed from measurements of urination frequency and bladder compliance (measured cystometrically). There was a very early onset of functional damage (within 2 weeks) when mice were reirradiated 9 months after a dose of 16 Gy. Lower initial doses of 8 Gy did not alter the time of expression of damage after reirradiation. The early damage was probably due to stimulated cellular proliferation, which occurred after 16 Gy but not after 8 Gy, causing rapid expression of retreatment injury. Reirradiation tolerance for late bladder damage was inversely related to the dose given in the first treatment but was independent of the interval between treatments. There was no evidence for increased tolerance as the interval between treatments increased from 1 day to 9 months, which suggests that protracting the overall treatment time will not lead to sparing of late radiation damage in the bladder.