A rat model of chemical-induced polycystic kidney disease with multistage tumors.

Diphenylthiazole (DPT) induces polycystic kidney disease in the rat which serves as a model of human acquired cystic disease of the kidney. However, DPT administration alone does not produce neoplastic changes in renal cysts. We examined the effect of N-nitrosomorpholine (NNM), a carcinogen, in rats bearing DPT-induced renal cysts. Forty Sprague-Dawley rats were divided into four groups: DPT/NNM, DPT, NNM, and nontreated groups. DPT was administered throughout the experimental period, and NNM was given from weeks 4 to 7 after the start of the experiment. The rats were sampled from weeks 39 to 48, and histopathological examinations of the excised kidneys were performed. Multiple cystic changes were observed in all the DPT-treated rats in both DPT and DPT/NNM groups which were absent in almost all other rats. Solid adenomatous lesions were observed in the NNM-treated rats: in 7 of 9 and in 3 of 10 rats in the DPT/NNM and NNM groups, respectively. Cystic adenomatous lesions were found in 4 of 9 rats in the DPT/NNM group exclusively and not in the other groups. Combined DPT and NNM administration to rats produced an animal model showing neoplastic changes in renal cysts resembling microscopically renal cancer lesions in human acquired cystic disease of the kidney (on hematoxylin and eosin staining).