Aspirin Inhibition of A/-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide- induced Lesions of the Urinary Bladder Correlated with Inhibition of Metabolism by Bladder Prostaglandin Endoperoxide Synthetase1

The effects of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) -induced urinary bladder lesions, endog enous bladder prostaglandin E2 synthesis, and the metabolism of FANFT by bladder epithelial microsomes were examined. Rats were fed 0.5% aspirin and/or a diet containing 0.1% or 0.2% FANFT. Bladder lesions were observed with light and scanning electron microscopy, and the prostaglandin E2 con tent of rat bladder was measured by radioimmunoassay. Me tabolism of FANFT was measured by decreased absorbance at 400 nm. Aspirin inhibited the appearance of hyperplastic le sions induced by feeding 0.1% or 0.2% FANFT for 6 or 12 weeks. Aspirin reduced bladder prostaglandin E2 content at 1, 2, 6, and 13 weeks compared to corresponding control values. Rat and rabbit microsomal metabolism of FANFT were depend ent upon specific fatty acid substrates and prevented by spe cific inhibitors (including aspirin) of prostaglandin endoperoxide synthetase. Other inhibitor and substrate specificity studies suggest that FANFT was not metabolized by xanthine oxidase, lipoxygenase, lipid peroxidation, or mixed-function oxidases. These results suggest that the metabolism of FANFT by pros taglandin endoperoxide synthetase may be involved in the metabolic activation of FANFT necessary for the induction of bladder cancer in rats.