Strong promoting activity by uracil on urinary bladder carcinogenesis and a possible inhibitory effect on thyroid tumorigenesis in rats initiated with N-methyl-N-nitrosourea

Uracil has been shown to cause a strong proliferative response in the urinary bladder epithelium of rats and mice through calculus formation and, consequently, acts as a strong promoter in bladder carcinogenesis. In this study, we examined the effect of uracil on two-stage carcinogenesis in various organs using N-methyl-N-nitrosourea (MNU) as the initiator. F344 rats were injected i.p. with MNU twice weekly for 4 weeks and then given diet containing 3.0% uracil for 20 weeks. Uracil induced urinary bladder carcinomas in all rats pretreated with MNU, and it decreased the combined incidence of adenomas and carcinomas in the thyroid. Although not significant, uracil decreased the incidence of adenomas in the lung and increased that of lymphomas of the thymus. A possible influence of a significantly decreased body weight gain caused by uracil treatment on the reduced tumor incidence in the thyroid and lung is discussed. The present data demonstrate the strong promotion activity of uracil for urinary bladder carcinogenesis, and suggest a possible inhibitory effect on thyroid carcinogenesis.