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.
Edrees
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G
Radiotherapy Department, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
Luts
A
A
Stewart
F
F
D000818:Animals; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000633:toxicity*; D005260:Female; D006417:Hematuria / Q000209:etiology; D051379:Mice; D008809:Mice, Inbred C3H; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000473:pathology*; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000528:radiation effects*; D014555:Urination Disorders / Q000209:etiology; D014965:X-Rays
D003520:Cyclophosphamide