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.

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