Proliferation-stimulating effect of phenacetin on the urothelium and papillary epithelium of rats.

In the present autoradiographic study, the effect of phenacetin (PH) on the proliferative activity of the urothelium and epithelium lining the renal papilla of rats was tested. The median 3H-thymidine-labeling index (3H-TdR index) of the bladder urothelium of rats daily fed PH for 2 years was twofold increased compared to untreated or initially partially cystectomized rats. The median 3H-TdR index of the papillary epithelium was 2-3 times higher than in untreated controls. The transitional epithelium of the renal pelves showed an approximately 2 times, and the urothelium of the ureters a 3 times increased median 3H-TdR index only when PH administration was combined with an initial one-third resection of the urinary bladder. Since after PH treatment the highest DNA synthesis consistently occurred in all rats with a resected bladder, it can be concluded that partial cystectomy increases the ability of the urothelium and the papillary epithelium to proliferate in response to the drug. The proliferation-stimulating effect of PH can be reconciled with a cocarcinogenic or promoting activity of the drug.