Early and Late Damage in the Mouse Bladder After Radiation Combined with Cyclophosphamide or Cisplatinum, Evaluated by two Different Functional Assays

Abstract

Early and late changes in the reservoir function of the mouse bladder were investigated after irradiation alone or combined with cisplatinum (cis-DDP) or cyclophosphamide (CTX). Bladder function was repeatedly assessed from independent assays of urination frequency and cystometry. Treatments consisted of 10-30 Gy x-rays alone or 10-22.5 Gy combined with chemotherapy (cis-DDP 6 mg/kg i.p. or CTX 100 mg/kg i.p.). Within 30 days after treatment, early damage was detected by both assays but the correlation between assays was significant only in the group treated with x-rays and CTX. The late response was irreversible and a correlation was found (p < 0.05) between urination frequency and the results of the cystometry assay in all treatment groups. After x-rays alone or x-rays plus cis-DDP, the RD50 values (the radiation dose that induced a response in 50% of the animals) decreased with time as damage occurred. After x-rays plus CTX, maximum damage appeared much earlier and RD50 values tended to increase from 12 to 40 weeks. Comparison of these RD50 values gave a dose-effect factor (the ratio between the RD50 doses for x-rays alone and x-ray plus drug) of 1.1 to 1.3 for cis-DDP in both assays. The enhancing effect of CTX on bladder reservoir function was greater, especially in the results of the frequency assay, as indicated by considerably lower RD50 values. This resulted in an estimated dose-effect factor of up to 2.4. In conclusion, both assays are suitable for investigating early and late bladder damage, although the functional defect measured is different. Both CTX and cis-DDP increased early and late bladder damage when combined with irradiation. Late damage appeared earlier in combined treatment groups than in mice treated with irradiation alone.