Carcinogenesis in heterotopically-transplanted urinary bladder by N-methyl-N-nitrosourea: a model for initiation and promotion.

The present investigation was conducted to establish a working model to evaluate the role of potential modifiers (promoters and inhibitors) of urinary bladder carcinogenesis. A single dose (0.25 mg) of the carcinogen N-methyl-N-nitrosourea (MNU) when instilled directly into heterotopically transplanted urinary bladder (HTB) induced a 9% (2 of 22) incidence of urinary bladder tumors by 30 weeks in the urine free HTB environment, whereas repeated instillation of urine into the HTB after MNU treatment resulted in a 61% (14 of 23) incidence of these tumors. Three doses of MNU (0.25 mg/dose once a week for 3 weeks) induced 33% (6 of 18) and 89% (16 of 18) incidence of tumors, respectively, in the absence and presence of urine in the HTB. These data confirm our previous observation that normal urine enhances urinary bladder carcinogenesis, and are consistent with the notion that normal urine exerts a tumor promoting effect.