Anaerobic metabolism and nuclear binding of the carcinogen 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT)

The anaerobic reductive metabolism of the urinary tract carcinogen2-amino-4-(5-nitro-2-furyl)-2-¹⁴C]-thiazole (¹⁴C]ANFT) wasexamined in vitro using rabbit liver and kidney microsomes.The intermediate(s) produced during the reduction binds to tRNA,DNA, and protein. ANFT reduction was inhibited by oxygen, requiredNADPH and was not inhibited by SKF-525A or allopurinol. No bindingto tRNA or DNA was observed if the nudeic acids were added atthe end of the incubation. The covalent binding of an ANFT metabolite(s)to nucleic acids and protein was inhibited by the antioxidantsvitamin E and butylated hydroxytoluene. The stoichiometry ofmicrosomal reduction shows 3 mol of NADPH were used/mol of ANFTreduced. In inner medullary microsomes, the apparent K_m andV_max were 0.05 mM and 0.92 nmol/mg/min, respectively. Two metabolitesfrom the anaerobic incubation of ANFT were isolated. The metaboliteswere tentatively identified as 1-(2-amino-4-thiazolyl)-3-cyano-1-propanoneand 2-amino-4-(5-hydroxylamino-2-furyl)thiazole.