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Metabolism of N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide by Prostaglandin Endoperoxide Synthetase¹

Geriatric Research, Education and Clinical Center, VA Medical Center, and Departments of Biochemistry and Medicine, St. Louis University, St. Louis, Missouri 63125

Cooxidative metabolism of the urinary bladder carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was examined using solubilized and particulate microsomal preparations from the rabbit renal inner medulla and the ram seminal vesicle. Metabolism was measured by the rate of decrease in absorbance at 400 nm. In these soluble and particulate preparations, FANFT metabolism was observed only in the presence of specific fatty acids. These fatty acids are substrates for prostaglandin endoperoxide synthetase. Structurally dissimilar inhibitors of prostaglandin endoperoxide synthetase such as indomethacin, aspirin, 5,8,11,14-eicosatetraynoic acid, ethoxyquin, and meclofenamic acid specifically inhibited FANFT metabolism. Other inhibitor and substrate specificity studies suggest that FANFT was not metabolized by nitroreductase, xanthine oxidase, lipoxygenase, lipid peroxidation, or mixed-function oxidases. In addition, the lack of detectable 2-amino-4-(5-nitro-2-furyl)thiazole formation suggests that arylformamidase was not participating in FANFT metabolism measured in these experiments. The data indicate that prostaglandin endoperoxide synthetase can mediate FANFT metabolism by a cooxidative process.

¹ This research was supported by the Veterans Administration.

² To whom requests for reprints should be addressed, at Geriatric Center (111G JB), VA Medical Center, St. Louis, Mo. 63125.

Received 6/11/79. Accepted 10/10/79.