EFFECTS OF SODIUM ASCORBATE, SODIUM SACCHARIN AND AMMONIUM-CHLORIDE ON THE MALE-RAT URINARY-BLADDER

Sodium saccharin administered at high doses to male rats beginning aft er 5 weeks of age produces mild urothelial hyperplasia but does not re sult in a significant increase in incidence of bladder cancer unless i t is administered after an initiating agent. However, if it is adminis tered in a two-generation bioassay, a significant incidence of bladder tumors is produced, The hyperplastic and tumorigenic effects are inhi bited by co-administration with high doses of NH4Cl. The present exper iment was designed to evaluate the effects of another sodium salt, sod ium ascorbate, administered through the neonatal time period, Sodium s accharin administered as 5% of the diet produced urothelial hyperplasi a and increased labeling index, and this was inhibited by co-administr ation with 1.23% NH4Cl. Four doses of sodium ascorbate were evaluated, The lowest dose, 0.91%, was without effect on the urinary tract, A sl ight effect (not statistically significant) was observed at a dose of 2.73%, and a significant proliferative response was detected at 4.56 a nd 6.84%. Recent studies suggest that a calcium phosphate-containing a morphous precipitate forms in the urine of rats fed high doses of sodi um 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 precipitat e and induction of urothelial proliferation were inhibited by co-admin istration of NH4Cl, but somewhat higher doses of ammonium chloride wer e 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 hyperplas ia in a dose responsive manner, with a no-effect level of 0.91% of the diet, The formation of the calcium phosphate-containing amorphous pre cipitate and urothelial proliferation were inhibited by co-administrat ion with NH4Cl.