Carcinogenesis in mammalian urothelium: changes induced by non-carcinogenic substances and chronic indwelling...

Carcinogenesis in urinary bladders may not be represented by a continuum of pathological lesions beginning with papillary tumors or flat dysplasias/atypias. In a previous experiment, sterile water and saline continuously infused via catheters connected to ALZA mini-pumps were shown to induce papillary urothelial lesions indistinguishable from tumors considered to be carcinomas in most histological classification schemes. The animals in the initial experiment were followed for relatively brief periods which did not allow for determination of potential reversibility of the process and did not distinguish the effects of the catheters versus those of the infused substances. The present study was designed to control for these variables. Rats were divided into seven groups to examine the urothelial changes after: surgery alone, continuous infusion of the sterile water and mitomycin C, and chronic indwelling catheters with and without infusion. The results indicated that chronic irritation with indwelling catheters was a strong stimulus for the induction of urothelial neoplasms and that continuous infusion of certain substances, even sterile water, might play a small role in the process of carcinogenesis. Comparing the frequencies of papillary urothelial tumors appearing after brief exposure to sterile water and catheters in the initial experiment (75 per cent) and papillary lesions appearing long after removal of the sterile water and catheters in the current study (0 per cent) indicates that these lesions are reversible and probably not neoplastic.