Carcinogenicity of uracil, a nongenotoxic chemical, in rats and mice and its rationale
Fukushima, S.; Tanaka, H.; Asakawa, E.; Kagawa, M.; Yamamoto, A.; Shirai, T.
Cancer Research 52(7): 1675-1680
1992
ISSN/ISBN: 0008-5472 PMID: 1551098 Document Number: 389194
In Experiment 1, groups of thirty 6-wk-old male and female F344 rats were given diets containing 0 (control) or 3% uracil for 104 wk. In the uracil-treated groups, carcinomas, in particular transitional cell carcinomas, 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 present in the urinary bladder of almost all males, but in only 30% of the females, and that induction of urinary bladder carcinomas was related to the presence of calculi. In Experiment 2, groups of thirty 6-wk-old male and female C57BL/6 .times. C3H F1 mice were given a diet containing 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 and 8% of the males. Squamous cell carcinomas developed in only 8% of the males. In Experiment 3, 6-wk-old male F344 rats were given diets containing 3% uracil, 3% uracil plus 5% or 10% NaCl, or 10% NaCl for 36 wk and then diet without chemical for a recovery period of 4 wk. The incidences of carcinomas and calculi of the urinary bladder were 75% and 81% in the group given uracil alone, 6% and 6% in the group given uracil plus 5% NaCl, and both zero in the group given uracil plus 10% NaCl. Thus, the present study showed that the inductions of urinary bladder carcinomas by uracil, a nongenotoxic compound, in rats and mice showed sex differences and were related to the presence of calculi in the urinary bladder.