CARCINOGENICITY OF URACIL, A NONGENOTOXIC CHEMICAL, IN RATS AND MICE AND ITS RATIONALE

In Experiment 1, groups of thirty 6-wk-old male and female F344 rats w ere given diets containing 0 (control) or 3% uracil for 104 wk. In the uracil-treated groups, carcinomas, in particular transitional cell ca rcinomas, developed in the urinary bladder of 90% of the males and 19% of the females. Squamous cell carcinomas also developed in 10% of the males, but not in females. Striking findings were that calculi were p resent in the urinary bladder of almost all males, but in only 30% of the females, and that induction of urinary bladder carcinomas was rela ted to the presence of calculi. In Experiment 2, groups of thirty 6-wk -old male and female C57BL/6 x C3H F1 mice were given a diet containin g 0 (control) or 3% (from Wk 1 to Wk 6) and 2.5% (from Wk 7 to Wk 96) uracil. The total observation period was 96 wk. In the uracil-treated groups, transitional cell carcinomas developed in 76% of the females a nd 8% of the males. Squamous cell carcinomas developed in only 8% of t he males. In Experiment 3, 6-wk-old male F344 rats were given diets co ntaining 3% uracil, 3% uracil plus 5% or 10% NaCl, or 10% NaCl for 36 wk and then diet without chemicals for a recovery period of 4 wk. The incidences of carcinomas and calculi of the urinary bladder were 75% a nd 81% in the group given uracil alone, 6% and 6% in the group given u racil plus 5% NaCl, and both zero in the group given uracil plus 10% N aCl. Thus, the present study showed that the inductions of urinary bla dder carcinomas by uracil, a nongenotoxic compound, in rats and mice s howed sex differences and were related to the presence of calculi in t he urinary bladder.