Fukushima S, Arai M, Cohen S M, Jacobs J B, Friedell G H
Lab Invest. 1981 Feb;44(2):89-96.
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.
通过光学显微镜、扫描电子显微镜和放射自显影术，研究了环磷酰胺对雄性F344大鼠膀胱的损伤。环磷酰胺以每千克体重50、75、100、150和200毫克的剂量腹腔注射，在治疗后的几个时间间隔处死大鼠。膀胱广泛坏死之后是上皮的再生性增生。在诱导的损伤数量和大小以及再生和修复时间方面，剂量反应明显。扫描电子显微镜显示，在增生早期，细胞腔表面有形态多样的微绒毛。分别在注射每千克75、100和200毫克环磷酰胺后的第2、5和7至8天，出现形态多样微绒毛的细胞数量最多。增生性病变的细胞表面也有短而均匀的微绒毛以及绳状或叶状微嵴。膀胱的放射自显影片显示，在增生早期上皮细胞有明显标记。在单次注射后存活超过1年的少数大鼠中，任何剂量水平下均无膀胱病变。将环磷酰胺注射后通过扫描电子显微镜观察到的上皮变化与膀胱癌发生过程中观察到的变化进行了比较。
