CO-OXIDATIVE METABOLISM OF 2-AMINO-4-(5-NITRO-2-FURYL)-THIAZOLE BY PROSTAGLANDIN HYDROPEROXIDASE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 96  (3) , 425-432
Abstract
Cooxidative metabolism of [the carcinogen] ANFT [2-amino-4-(5-nitro-2-furyl)-thiazole] by the fatty acid cyclo-oxygenase or hydroperoxidase activities of prostaglandin endoperoxide synthetase was examined using solubilized and particulate microsomes prepared from rabbit renal inner medulla and ram seminal vesicles. The rate of metabolism was measured by the decrease in absorbance at 385 nm. In soluble and particulate preparations, ANFT metabolism was dependent upon specific fatty acid substrates and prevented by specific inhibitors of prostaglandin endoperoxide synthetase. Other inhibitor and substrate specificity studies suggest that ANFT was not metabolized by xanthine oxidase, lipoxygenase, lipid peroxidation or mixed-function oxidases. Under incubation conditions which demonstrated cooxidation of ANFT, a metabolite (peak 1) was observed by high-pressure liquid chromatography. In the presence of indomethacin, peak 1 was not present, and only authentic ANFT was observed. Cooxidation of ANFT was also observed with cumene hydroperoxide. Cumene hydroperoxide-mediated cooxidation was not prevented by indomethacin or SKF-525-A but was blocked by the antioxidants butylated hydroxytoluene, ethoxyguin and vitamin E. ANFT is metabolized by a cooxidative process involving the prostaglandin hydroperoxidase activity of prostaglandin endoperoxide synthetase.