Effect of dose on urinary bladder carcinogenesis induced in F344 rats by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.

Because of the utility of the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) rat model in the study of bladder cancer, the effect of dose on FANFT-induced bladder carcinogenesis was evaluated. Weaning male F344 rats were given FANFT in the diet at doses of 0.1, 0.05, 0.01, 0.005, 0.001, and 0.0005% for 30 weeks and then a control diet for 22 weeks. A control group received only the control diet throughout the experiment. Papillary tumors were present at the higher doses, hyperplasia of various degrees of severly was present at the intermediate doses, and minimal hyperplasia was observed in 4 of 16 rats at the 0.005% dose; no mucosal abnormalities were observed at the two lower doses or in the control group. Bladder epithelium from selected animals was also examined by scanning electron microscopy (SEM) after 10 weeks and again at the end of the experiment. Hyperplastic mucosa with pleomorphic microvilli similar to that previously demonstrated for 0.2% FANFT was observed at 10 weeks in rats fed 0.1% FANFT. Hyperplastic mucosa with pleomorphic microvilli was also observed at 52 weeks in rats fed 0.1% and 0.05% FANFT. Hyperplastic mucosa without pleomorphic microvilli was observed in rats fed 0.01 and 0.005% FANFT. The bladder appeared normal by light microscopy and SEM at the two lower doses and in the control group at both the 10- and 52-week intervals. A dose relationship was thus demonstrated for FANFT-induced bladder carcinogenesis in male F344 rats, and more severe surface changes were observed by SEM as the dose increased.