A renal carcinogen causes inhibition of cyst formation in the Cy rat model of polycystic kidney disease

In the Han:SPRD-Cy/+ rat model of polycystic kidney disease (PKD). increased proliferation of tubular epithelial cells has been noted in histological investigations. However, the role of ceil proliferation in cystogenesis is not yet clear. In the present study, to assess tho relation between carcinogenesis and cystogenesis, we exposed Cy heterozygous rats to N-ethyl-N-hydroxyethylnitrosamine (EHEN), which selectively induces Jatypical tubules, atypical hyperplasia and tumors in the kidneys. Although PKD normally-progressed to the terminal stage in Cy heterozygous animals, induction of preneoplastic lesions with EHEN was associated with attenuation in the initial state of cyst formation. Thus, the prevalence of small initial cysts and epithelial hyperplasia in the kidneys of the EHEN-treated group was greater that in the untreated group which had many well-developed cysts. The Cy heterozygous rats with papillary macroadenomas demonstrated pronounced inhibition of large cyst formation and reduction in the serum urea nitrogen and creatinine levels, consistent with improved renal function. We conclude that the administration of a renal carcinogen interferes with the progressive enlargement of tubular cysts in rats with an autosomal dominant type of polycystic kidney disease.