Peroxidase metabolism of the urinary bladder carcinogen 2-amino-4-(5-nitro-2-furyl)thiazole.

Metabolism of 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) by a variety of different peroxidases was examined. Metabolism of ANFT was measured by the binding of radiolabeled substrates to protein and DNA. Prostaglandin hydroperoxidase but not horseradish peroxidase, lactoperoxidase, or chloroperoxidase metabolically activated ANFT. All four peroxidases catalyzed the binding of benzidine to protein and DNA. With peroxide substrates, peroxidase-catalyzed binding of both carcinogens was observed with or without molecular oxygen. Arachidonic acid-dependent binding of ANFT and benzidine by prostaglandin endoperoxide synthetase was inhibited by anaerobic conditions and aspirin. Chloroperoxidase activation of benzidine was also inhibited by aspirin. Vitamin E inhibited activation of both carcinogens by all enzymes examined. Prostaglandin hydroperoxidase-catalyzed binding of benzidine to protein was inhibited by the 5-nitrofurans ANFT and 3-hydroxymethyl-1-(([3-(5-nitro-2-furyl)allydidene] amino))hydantoin and acetaminophen, while only acetaminophen inhibited horseradish peroxidase-catalyzed binding. These results indicate that different peroxidases may exhibit specificity with respect to their activation of carcinogens. Only prostaglandin hydroperoxidase activated the 5-nitrofuran ANFT, while a number of peroxidases activated the aromatic amine benzidine.