Renal Tubular Cyst Formation in Newborn Rats Treated with p-Cumylphenol

In this study, we investigated the sequential changes in the development of renal tubular cysts in newborn rats treated with p-cumylphenol (PCP). Fifteen animals per sex were treated orally with 300 mg/kg/day of PCP for up to 18 days from postnatal day (PND) 4 and were sacrificed on PNDs 8, 12, 19 and 22 and after a 7 day recovery period. On PNDs 8 and 12, slight dilatation of the collecting ducts was frequently observed in the medulla and slight papillary necrosis was also noted in some cases. These dilated collecting ducts were lined with slightly hyperplastic epithelial cells. On PNDs 19 and 22, multiple large cystic changes arising from the collecting ducts in the outer medulla were seen. These cystically dilated ducts were also lined with hyperplastic epithelial cells. During the dosing period, the labeling index of proliferating cell nuclear antigen in the collecting duct epithelium was higher in the PCP-treated group than in the control group at all time points. After a 7 day recovery period, the cystic change still remained, although the cell density was decreased and the epithelial cells became flattened. On the other hand, basophilic tubules with peritubular lymphoid cell infiltration were multifocally observed in the cortex. In conclusion, PCP induced multiple renal cysts that developed in the collecting ducts of the outer medulla in neonatal rats, and it is suggested that epithelial cell proliferation may play some roles in the induction of cystic lesions. (J Toxicol Pathol 2009; 22: 125-131)