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.