Reductive metabolism of the carcinogen 4-(5-nitro-2-furyl)thiazole to 1-(4-thiazolyl)-3-cyano-1-propanone by rat liver subcellular fractions

The reductive metabolism of 4-(5-nitro-2-furyl)thiazole (NFT), a rat mammary gland and forestomach carcinogen, was examined in vitro using rat liver tissues. NFT was reduced by rat liver cytosol or microsomes on anaerobic incubation with NADPH. The stoichiometry of microsomal reduction revealed that about 3 moles of NADPH were used per mole of NFT. Gas chromatographic analysis of the reaction mixture showed a major peak with a retention time of about 4.0 min in contrast to NFT with a retention time of about 6.5 min. Catalytic hydrogenation of NFT with palladium and activated carbon yielded a product with a retention time of 4.0 min. The component corresponding with the above metabolite was isolated from chemically reduced NFT and identified as 1-(4-thiazolyl)-3-cyano-l-propanone. The metabolite derived from enzymatic reduction had chromatographic and spectral properties and a mass spectral fragmentation pattern similar to those obtained chemically. These data establish that the enzymatically derived product is identical to that obtained by chemical reduction and that it corresponds to 1(4thiazolyl)3cyano1propanone.