Sodium saccharin administered at high doses to male rats beginning after 5 weeks of age produces mild urothelial hyperplasia but does not result in a significant increase in incidence of bladder cancer unless it is administered after an initiating agent. However, if it is administered in a two-generation bioassay, a significant incidence of bladder tumors is produced. The hyperplastic and tumorigenic effects are inhibited by co-administration with high doses of NH4C1. The present experiment was designed to evaluate the effects of another sodium salt, sodium ascorbate, administered through the neonatal time period. Sodium saccharin administered as 5% of the diet produced urothelial hyperplasia and increased labeling index, and this was inhibited by co-administration with 1.23% NH4CI. Four doses of sodium ascorbate were evaluated. The lowest dose, 0.91%, was without effect on the urinary tract. A slight effect (not statistically significant) was observed at a dose of 2.73%, and a significant proliferative response was detected at 4.56 and 6.84%. Recent studies suggest that a calcium phosphate-containing amorphous precipitate forms in the urine of rats fed high doses of sodium saccharin, producing cytotoxicity of the urothelium and consequent regenerative hyperplasia. This precipitate was observed in the present experiment in the rats administered the high dose of sodium saccharin or the higher doses of sodium ascorbate. Formation of this precipitate and induction of urothelial proliferation were inhibited by co-administration of NH4Cl, but somewhat higher doses of ammonium chloride were required for doses of sodium ascorbate compared to sodium saccharin. These results demonstrate that sodium ascorbate administered through the neonatal time period of the male rat produces urothelial hyperplasia in a dose responsive manner, with a no-effect level of 0.91% of the diet. The formation of the calcium phosphate-containing amorphous precipitate and urothelial proliferation were inhibited by co-administration with NH4Cl.
ASJC Scopus subject areas
- Cancer Research