Scanning electron microscopy of cyclophosphamide-induced hyperplasia of the rat urinary bladder

Urinary bladder damage caused by cyclophosphamide in male F344 rats was studied by light microscopy, scanning electron microscopy, and autoradiography. Cyclophosphamide was injected intraperitoneally at doses of 50, 75, 100, 150, and 200 mg. per kg. of body weight, and rats were killed at several intervals following treatment. Extensive necrosis of the bladder was followed by regenerative hyperplasia of the epithelium. A dose response was evident in the number and size of lesions induced and the time of regeneration and repair. Scanning electron microscopy disclosed pleomorphic microvilli on the luminal surface of cells during the early phases of hyperplasia. The greatest number of cells with pleomorphic microvilli occurred 2, 5 and 7 to 8 days following injection of 75, 100, and 200 mg. per kg. of cyclophosphamide, respectively. The hyperplastic lesions also had cells with short, uniform microvilli and ropy or leafy microridges on their surfaces. Autoradiographs of the urinary bladders showed marked labeling of epithelial cells in the early phase of hyperplasia. Of the few rats surviving beyond 1 year after a single injection, none had bladder lesions at any of the dose levels. The changes in the epithelium observed by scanning electron microscopy following cyclophosphamide injection were compared to those observed during bladder carcinogenesis.