This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mattammal, M. B. Articles by Davis, B. B. Search for Related Content PubMed PubMed Citation Articles by Mattammal, M. B. Articles by Davis, B. B.

Prostaglandin Hydroperoxidase-mediated 2-Amino-4-(5-nitro-2-furyl) [¹⁴C]thiazole Metabolism and Nucleic Acid Binding¹

Geriatric Research, Education, and Clinical Center, Veterans Administration Medical Center, St. Louis 63125 [M. B. M., T. V. Z., B. B. D.], and Departments of Biochemistry [T. V. Z.] and Medicine [M. B. M., T. V. Z., B. B. D.], St. Louis University, St. Louis, Missouri 63106

Prostaglandin hydroperoxide-mediated metabolism and binding of 2-amino-4-(5-nitro-2-furyl) [¹⁴C]thiazole ([¹⁴C]ANFT) metabolite to nucleic acids and proteins were investigated with rabbit bladder transitional epithelial and solubilized ram seminal vesicle microsomes. Metabolism was assessed by spectrophotometric and radiochemical techniques. Substrate and inhibitor studies are consistent with both metabolism and binding of [¹⁴C]ANFT occurring by the prostaglandin hydroperoxidase activity of prostaglandin endoperoxide synthetase. The ratio of the rates of [¹⁴C]ANFT product formation is approximately 3:7:10 (organic soluble:non-trichloroacetic acid precipitable: trichloroacetic acid precipitable) over a wide range of arachidonic acid concentrations. Approximately 2 and 1% of the total [¹⁴C]ANFT metabolized binds to transfer RNA and DNA, respectively. The metabolite isolated from the organic phase had a chromatographic profile and ultraviolet spectra different from authentic ANFT. If transfer RNA or DNA is added at the end of a 5-min incubation, no binding to nucleic acids was observed. The demonstration of prostaglandin hydroperoxidase-mediated covalent binding to nucleic acids is consistent with the involvement of this enzyme in 5-nitrofuran-induced bladder carcinogenesis.

¹ This work was supported by the Veterans Administration, Cancer Research Institutional Committee Grant from St. Louis University, and USPHS Grant CA-28015 from the National Cancer Institute through the National Bladder Cancer Project.

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

Received 5/ 7/81. Accepted 9/ 2/81.