Induction of tumors in heterotopic bladder by topical application of N-methyl-N-nitrosourea and N-butyl-N-(3-carboxypropyl)nitrosamine.

ABSTRACT

The heterotopic urinary bladder with a communicating reservoir is a potentially useful model for bladder carcinogenesis studies. As a test of whether such bladders will develop transitional cell carcinomas after chronic carcinogenic stimuli, two carcinogens, N-methyl-N-nitrosourea and N-butyl-N-(3-carboxypropyl)nitrosamine, were instilled repeatedly into the reservoir connected with the heterotopic bladder. Transitional cell carcinomas developed in 25 of 33 heterotopic bladders exposed to cumulative doses of 1.5, 3.0, or 6.0 mg of N-methyl-N-nitrosourea for between 20 and 30 weeks, while heterotopic bladders exposed to cumulative doses of 150 or 300 mg of N-butyl-N-(3-carboxypropyl)nitrosamine failed to develop tumors. However, 11 of 27 rats with heterotopic bladders that were exposed to N-butyl-N-(3-carboxypropyl)nitrosamine for over 20 weeks developed tumors in their homotopic or natural bladders. N-Methyl-N-Nitrosourea probably acted directly on the bladder epithelial cells to induce neoplastic change. The reason(s) for the development of tumors in homotopic but not heterotopic bladders when N-butyl-N-(3-carboxypropyl)nitrosamine was administered directly into the heterotopic bladders could not be ascertained from these studies.