Effect of aspirin on urinary bladder carcinogenesis initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in rats

N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT), a potent urinary bladder carcinogen, is metabolically activated in vitro by a variety of enzyme systems including aerobic cooxidation by prostaglandin H synthase which is present in the rat bladder mucosa. In a previous experiment, aspirin coadministered with FANFT for 12 weeks inhibited FANFT-induced bladder carcinogenesis and enhanced forestomach carcinogenesis. To further evaluate the effects of aspirin on FANFT carcinogenesis, male F344 rats were fed either FANFT (0.2% of the diet) for 12 weeks (Group 4), aspirin (0.5% of the diet) simultaneously with FANFT for 12 weeks (Group 2), aspirin simultaneously with FANFT for 12 weeks and then subsequently to the end of the experiment (Group 1), or FANFT only followed by aspirin (Group 3). The incidence of bladder carcinoma was significantly higher when aspirin was fed after FANFT treatment (87%) compared to FANFT followed by control diet (48%) and was higher in rats given aspirin plus FANFT followed by aspirin (73%) compared to aspirin plus FANFT followed by control diet (47%). Aspirin alone given for 13 weeks (Group 6) or throughout the experiment (68 weeks) (Group 5) did not induce bladder cancer. However, in all groups administered aspirin long-term, renal papillary necrosis and renal pelvic hyperplasia and atypia were frequently observed. Only a single forestomach tumor was observed. In the present experiment, aspirin appeared to exhibit promoting activity for bladder carcinogenesis in the rat.