Bladder damage in mice after combined treatment with cyclophosphamide and X-rays. The influence of timing and sequence.

The response of the mouse bladder to single doses of cyclophosphamide (CY), X-rays, or their combination was assessed from the development of functional damage (haematuria and increased frequency of urination). For the combined treatments, a single dose of CY (100 mg.kg-1) was given immediately before or at intervals of up to 9 months before irradiation, or at one week to 9 months after irradiation. Damage after X-rays alone was expressed late, with no functional changes earlier than 5 months. CY alone, by contrast, caused a marked increase in urination frequency and haematuria within one week. There was subsequently partial recovery although some residual damage persisted for at least one year. CY given before or after X-rays caused an early, X-ray dose-related expression of damage. These results suggest that the drug precipitated some of the latent radiation injury. There was also a second wave of damage after the combined treatments and the response at 9-12 months was always more severe than after X-rays alone. This increased late damage could be explained in terms of additive drug and radiation toxicities. Since drug given up to 9 months before or after irradiation caused more severe bladder damage than X-rays alone, CY should be avoided in clinical situations where the bladder has been irradiated.