膀胱発癌物質N-〔4-(5-Nitro-2-furyl)-2-thiazolyl〕-formamideのラット尿中代謝産物の検討

Abstract

N-(4-(5-Nitro-2-furyl)-2-thiazolyl) formamide (FANFT) demonstrated carcinogenic activity for the urinary bladder of many species. The present study sought the metabolites of FANFT in the urine of rats fed this compound, and determined their mutagenic activity for Salmonella typhimurium TA100. Three yellow FANFT metabolites, designated as FM I, FM 2 and FM 3, were present in urine and could be separated by polyvinylpyrrolidone column chromatography or cellulose thin layer chromatography (TLC). The Rf values on cellulose TLC were 0.89, 0.19 and 0.37 (aqueous 2% methanol) or 0.40, 0.30 and 0.14 (aqueous 6% acetic acid) for FM 1, FM 2 and FM 3, respectively. FM 2 was identified as 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) by comparison with authentic ANFT. Three rats were fed a diet containing 0.188% FANFT for 1 week and then were injected i.p. with [14C]FANFT. The urine excreted during 24 hours was analyzed by radiochromatography on cellulose plates (aqueous 2% methanol). About 33%, 30% and less than 5% of the radioactivity in the urine were respectively accounted for FM I, FM 2, and FM 3, and no [14C]FANFT could be detected. The cellulose chromatogram was cut into 1cm long pieces, and each piece was placed in the center of a petri dish containing Salmonella typhimurium TA100. Only FM 2 (ANFT) clearly demonstrated mutagenic activity. These data suggest that ANFT may be a proximate metabolite responsible for the induction of bladder cancer in rats fed FANFT.