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Modulation of Epdxide Hydrolase Activity; Effect on the Activation of Benzo Cal Pyrene and Its Covalent Binding to Dna in the Nucleus

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Biological Reactive Intermediates—II

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 136))

Abstract

Benzo[a]pyrene (BP), a model polycyclic aromatic hydrocarbon mutagen and carcinogen, requires bioactivation for the expression of its carcinogenic and mutagenic properties. This process occurs in multiple steps, the initial step being a conversion of BP to epoxide(s) by membrane-bound monooxygenases. The subsequent disposition of these electrophilic species can be directed towards toxic or nontoxic endpoints, depending upon the relative preponderance of several enzymatic and nonenzymatic processes within the cell. Epoxides formed from BP can rearrange to form phenols, be conjugated to glutathione, be converted by epoxide hydrolase to dihydrodiols or bind to cellular macromolecules (Jerina and Daly, 1974; Yang, et al., 1978; Lu and Miwa, 1980; Guenthner and Oesch, 1980a). Such binding to DNA is considered to be the crucial initiating step of BP carcinogenesis (Sims and Grover, 1974; Heidelberger, 1975).

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Authors and Affiliations

  1. Department of Pharmacology, University of Mainz, D-6500, Mainz, Deutschland

    Thomas M. Guenthner & Franz Oesch

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  1. Thomas M. Guenthner
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  2. Franz Oesch
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Editors and Affiliations

  1. Rutgers University, Piscataway, New Jersey, USA

    Robert Snyder , Charlotte M. Witmer  & Beatrice N. Engelsberg ,  & 

  2. Medical University of South Carolina, Charleston, South Carolina, USA

    David J. Jollow  & Stephen L. Longacre  & 

  3. University of Surrey, Guildford, Surrey, England

    Dennis V. Parke  & C. Gordon Gibson  & 

  4. Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    James J. Kocsis  & George F. Kalf  & 

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© 1982 Springer Science+Business Media New York

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Guenthner, T.M., Oesch, F. (1982). Modulation of Epdxide Hydrolase Activity; Effect on the Activation of Benzo Cal Pyrene and Its Covalent Binding to Dna in the Nucleus. In: Snyder, R., et al. Biological Reactive Intermediates—II. Advances in Experimental Medicine and Biology, vol 136. Springer, New York, NY. https://doi.org/10.1007/978-1-4757-0674-1_52

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  • DOI: https://doi.org/10.1007/978-1-4757-0674-1_52

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  • Print ISBN: 978-1-4757-0676-5

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