Prostaglandin H synthase metabolism of the urinary bladder carcinogens benzidine and ANFT

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Abstract
Prostaglandin H synthase (PHS) and horseradish peroxidase catalyze the oxidation of benzidine to the same free radical species. No radical was observed if either benzidine, H 2 O 2 or enzyme was omitted. The similarity of the fine structure of this radical to a computer-simulated model suggests the presence of a free cation radical of benzidine. Neither super-oxide nor hydroxyl radicals appear to be involved in the cooxidation of benzidine or 2-amino-4-(5-nitro-2-furyl)-thiazole (ANFT) by PHS. Production of the benzidine radical by PHS was inhibited by ANFT, acetaminophen, cyanide and ascorbate. ANFT was metabolized by PHS but not by horseradish peroxidase. ANFT had no effect on either radical production or 14 C-metabolism of benzidine by horseradish peroxidase. These results indicate that different peroxidases may exhibit specificity with respect to the carcinogens they activate. The free radical cation of benzidine may be the electrophilic intermediate responsible for PHS-catalyzed binding of benzidine to protein and nucleic acids.