Inhibition by aspirin of N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide-induced bladder carcinogenesis and enhancement of forestomach carcinogenesis.

Abstract

N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT) is a potent urinary bladder carcinogen in the rat, and it can be metabolically activated in vitro by a variety of enzyme systems including aerobic cooxidation by prostaglandin H synthase. The latter enzyme is present in the rat bladder mucosa and can be inhibited by the oral administration of aspirin (ASA). To determine if ASA could inhibit the bladder carcinogenicity of FANFT, FANFT (0.2%) was co-administered in the diet with ASA (0.5%) for 12 weeks followed by 1 week of ASA only and then 56 weeks on control diet. 0.2% FANFT followed by control diet induced bladder carcinomas in 18 of 21 (87%) rats, but when ASA was co-administered, only 10 of 27 (37%) rats developed bladder carcinoma (p less than 0.001). However, forestomach tumors, not seen in rats fed only FANFT, developed in 7 rats fed FANFT plus ASA. No tumors occurred in control rats or those fed only ASA. Possible mechanisms, including the role of prostaglandin H synthase in FANFT metabolism, are discussed.