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

  • Thomas M. Guenthner
  • Franz Oesch
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

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).

Keywords

Epoxide Hydrolase Polycyclic Hydrocarbon Microsomal Epoxide Hydrolase Epoxide Hydrolase Activity Ultimate Carcinogen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Thomas M. Guenthner
    • 1
  • Franz Oesch
    • 1
  1. 1.Department of PharmacologyUniversity of MainzMainzDeutschland

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