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 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 x 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 chemicals 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.
Fukushima
S
S
First Department of Pathology, Nagoya City University Medical School, Japan.
Tanaka
H
H
Asakawa
E
E
Kagawa
M
M
Yamamoto
A
A
Shirai
T
T
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012727:Sex Characteristics; D013045:Species Specificity; D014498:Uracil / Q000633:toxicity*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology
D002273:Carcinogens; D014498:Uracil