Uracil-induced calculi and proliferative lesions of the mouse urinary bladder

Uracil fed as 3% of the diet to rats produces urinary calculi and consequent proliferative lesions of the bladder epithelium, including papillomatosis. We evaluated the effects of dietary uracil in two strains of mice and compared the results in males and females. Uracil was fed as 3 or 1% of the diet to male and female Swiss and C3H mice for up to 20 weeks. The 3% dose produced marked proliferative changes in the bladder epithelium by 10 weeks of administration, the earliest time at which the animals were processed for microscopic evaluation. These lesions progressed to severe nodular and papillary hyperplasia so that all of the animals fed 3% uracil had to be killed by the end of the 15th week. These animals had uracil-formed calculi. In contrast, mice fed 1% uracil rarely developed uracil calculi, and also rarely developed proliferative changes in the bladder epithelium as observed by light microscopy. Also, the labeling index was determined and showed quantitatively the degree of cell proliferation similar to that qualitatively observed by light microscopic examination. At 10 weeks of administration, there was an increased labeling index in the males compared to females in both strains of mice fed 3% uracil, but this difference was not significant at 15 weeks. Similarly, the males tended to have more severe histologic changes than the females. The results of feeding high doses of uracil are similar in mice to those previously observed in rats.