PROMOTING EFFECT OF SACCHARIN AND DL-TRYPTOPHAN IN URINARY-BLADDER CARCINOGENESIS

Abstract

The existence of at least 2 stages in bladder carcinogenesis was evaluated in male Fischer rats using N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) fed for 6 wk at a level of 0.2% of the diet as the initiator. Sodium saccharin and DL-tryptophan were fed at levels of 5 and 2% of the diet, respectively, as possible promoting chemicals, and they were fed either immediately after FANFT administration or after 6 wk of FANFT plus 6 wk of control diet. All surviving rats were killed at the end of 2 yr. Both chemicals significantly increased the incidence of bladder tumors following FANFT feeding compared to 6 wk of FANFT feeding followed by control diet and the results were similar whether saccharin or tryptophan feeding was started immediately after FANFT feeding was concluded or after a 6 wk delay. Saccharin was considerably more potent as a promoting agent than was tryptophan, inducing higher incidences of bladder tumors and having a shorter latent period. Long-term administration of FANFT induced a 100% incidence of bladder cancer. Sequential epithelial changes were observed by scanning and transmission electron microscopy and by light microscopy. Pleomorphic microvilli were present on the superficial cells of all tumors examined and on the surface cells of hyperplastic bladder epithelium after 6 wk of FANFT plus 6 wk of saccharin, but not after 6 wk of FANFT and 6 wk of control diet. Rats fed only saccharin, tryptophan or control diet did not have bladder tumors or pleomorphic microvilli on bladder epithelium. Saccharin and tryptophan might act as tumor-promoting agents during bladder carcinogenesis.