Uracil-induced urolithiasis and the development of reversible papillomatosis in the urinary bladder of F344 rats

Abstract

Male F344 rats were given a diet supplemented with uracil at concentrations of 1 or 3% for 15 or 30 wk. In the group given 3% uracil, numerous calculi of uracil were observed in the urinary tract with marked hyperplasia and papillomas of the urinary bladder mucosa in Wk 15 and 30. In Wk 30, dysplasia of the ureteral mucosa and one transitional cell carcinoma of the bladder were also found. Neither these marked proliferative lesions nor calculi except for one papilloma were observed in rats maintained on normal basal diet for 15 wk after a diet containing 3% uracil for 15 wk. In the group given 1% uracil, no calculi or hyperplasia was seen in Wk 15 (five rats), and only one of ten rats examined in Wk 30 had a few stones and mild epithelial hyperplasia of the bladder. Scanning electron microscopy showed that most surface cells of papillomas had numerous short uniform microvilli and ropy rounded microridges. By transmission electron microscopy, epithelial cells of papillomas showed essentially normal differentiation. The present findings suggested that most hyperplasias and papillomas induced by bladder stones were reversible.