PMID: 2945250Jan 1, 1986Paper

Sequential morphologic analysis of the nephrotoxicity produced in rats by single doses of chlorozotocin

Toxicologic Pathology
J H Dees, R A Kramer


Chlorozotocin is a chloroethylnitrosourea antitumor agent that is in clinical trial for a variety of human tumors. Renal failure has been a reported side effect of treatment with several of the chloroethylnitrosoureas, including chlorozotocin. To better understand the pathogenesis of this target organ toxicity, we have studied the nephrotoxicity of a single high, intermediate, or low dose of chlorozotocin in male F344 rats. We report here the sequence of histopathologic changes seen over a 1-10-day (high dose) or 1-28-day (intermediate or low dose) period. The single high dose (40 mg/kg, s.c.) produced an acute cortical necrosis involving the proximal tubules, followed by later necrotic changes in the collecting ducts in the inner medulla. Karyomegaly was noted at 10 days in occasional cells of the papillary collecting ducts and urinary epithelium lining the papilla. A single intermediate dose (25 mg/kg, s.c.) caused a similar but less severe injury of later onset. Proximal tubule injury was less severe and more limited. Necrosis of papillary collecting ducts was not seen; however, karyomegaly was pronounced in cells of the collecting ducts in the inner stripe of the outer medulla and inner medulla, and in the urinary epitheliu...Continue Reading


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