Sequential studies of rat urinary bladder epithelial lesions induced by ifosfamide (Z4942)

Urinary bladder damage caused by ifosfamide in male F344 rats was studied by light microscopy and scanning electron microscopy. Ifosfamide was injected intraperitoneally at doses of 30, 60 and 120 mg. per kg. body weight, and rats were killed at several intervals following treatment. The changes in the epithelium observed by light microscopy and scanning electron microscopy following ifosfamide injection were compared to those observed following cyclophosphamide injection. Necrosis and exfoliation of the urinary bladder epithelium occurred after day 1 of ifosfamide treatment and were followed by regenerative hyperplasia. This hyperplasia was reversible. A dose response was evident in the number and size of lesions induced and the time of regeneration and repair. Scanning electron microscopy disclosed short, uniform microvilli on the luminal surface of cells during the early phases of hyperplasia. These microvilli persisted for only 1 day, from days 1 to 7, and days 1 to 12 respectively, following injection of 30, 60 and 120 mg. per kg. of ifosfamide. The hyperplastic lesions also contained cells with pleomorphic microvilli and ropy or leafy microridges on their surfaces. These findings after ifosfamide administration were similar to those reported to be induced in the urinary bladder by cyclophosphamide.