Radiation tolerance of normal mouse bladders after intravesical chemotherapy

The aim of this study was to compare functional damage in normal mouse bladder after various initial intravesical therapies and to investigate tolerance to subsequent irradiation. Six consecutive weekly intravesical instillations of Mitomycin C (MMC) or doxorubicin (DOX) were used as the initial therapy. Irradiation with single doses of 10-25 Gy (X-rays) was given at 4 or 12 weeks after intravesical treatment. Functional bladder damage was assessed from changes in the micturition frequency, expressed as frequency index (FI, number of urination events/ml urine in a 24-h test period) and from cystometry measurements of bladder volume at 52-56 weeks. Irradiation alone caused a temporary acute response (increased FI) within the first 4 weeks and a progressive late response starting from 15 to 37 weeks, depending on the radiation dose. A reduced bladder capacity was also evident at 52-56 weeks after 25 Gy. Intravesical MMC or DOX caused a 3-fold increase in FI during intravesical therapy with recovery to control levels within 2-3 weeks after cessation of treatment. Irradiation 4 weeks after MMC, or 4 or 12 weeks after DOX resulted in acute responses very similar to irradiation alone. There was no difference in time of onset or extent of late bladder damage when irradiation was given after DOX, compared with irradiation alone as assessed from repeated measurements of FI or cystometry at 52-56 weeks. In contrast, irradiation 12 weeks after MMC led to a decrease in acute radiation response compared with X-rays alone.(ABSTRACT TRUNCATED AT 250 WORDS)