The combined effect of mechanical trauma and phenacetin or sodium saccharin on the rat urinary bladder

The effect of 0.535% phenacetin or 5% sodium saccharin administered in the diet on proliferating urothelium in 160 Sprague-Dawley rats was studied by light microscopy and scanning electron microscopy. Reparative urothelial proliferation was induced by perforating the urinary bladder with a 23 gauge needle. The rats were then treated with phenacetin or sodium saccharin for up to 70 weeks. Non-perforated rats treated with phenacetin or sodium saccharin developed a slowly increasing urothelial hyperplasia detectable by light microscopy and SEM examination. When the rats were subjected to perforation of the bladder followed by phenacetin or sodium saccharin there was a significant increase in the incidence and severity of the hyperplastic lesions compared to rats treated with phenacetin or sodium saccharin alone. Although pleomorphic microvilli were detected on the luminal surface of the bladder in 30 of 160 rats, only 2 rats developed bladder tumors. Among female rats pleomorphic microvilli, although initially frequently present, seemed to disappear. The presence of pleomorphic microvilli therefore seems also to be consistent with a reversible hyperplasia.