Year-end Sale % OFF 
Abstract
Although the peroxidative metabolism of benzidine and other carcinogenic arylamines has been regarded as a significant pathway in extrahepatic tissues, the mechanism of peroxidase-mediated covalent binding to DNA has remained unclear. In this study, we have compared the metabolic activation of benzidine by prostaglandin H synthase, horseradish peroxidase, chloroperoxidase, and lactoperoxidase. All four peroxidases mediated the binding of benzidine to DNA and equimolar amounts of hydrogen peroxide (or arachidonic acid) and benzidine were required for the maximal binding in the system with either horseradish peroxidase or prostaglandin H synthase. In reactions containing both synthetic [3H]benzidine diimine and [14C]benzidine, rapid equilibration of both compounds was evident through the formation of its charge-transfer complex and the 14C-associated binding to DNA. However, the total binding (3H and 14C) correlated with the concentration of benzidine diimine rather than that of the charge-transfer complex. Two major and one minor deoxyguanosine adducts (P-I, P-III and P-IV, respectively) were isolated after the enzymatic hydrolysis of the benzidine-modified DNA. P-I was identified as N-(deoxyguanosin-8-yl)-benzidine, which was the major adduct formed by reaction of benzidine diimine with DNA. P-IV, which was also formed on reaction of benzidine diimine with DNA, was consistent with an N-(deoxyguanosin-N2-yl)-benzidine structure. P-III, which was formed only in the peroxidase incubations with DNA, was characterized as a novel N,3-(deoxyguanosin-N7,C8-yl)-benzidine derivative. Furthermore, this DNA adduct was shown to arise by the action of the peroxidase on DNA that had been previously modified by benzidine diimine. These results indicate that the two-electron oxidation product of benzidine, benzidine diimine, is the predominant reactive intermediate for the DNA binding mediated by peroxidases.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
