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Fate of Epdxides

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Book cover Biological Reactive Intermediates—II

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

Abstract

One of the most important reactions of epoxides appears to be the covalent binding to DNA which can lead to mutagenicity and is strongly suspected to be the primary lesion ultimately leading to initiation of cancer (Miller and Miller, 1974; Oesch, 1973; Jerina and Daly, 1974; Sims and Grover, 1974; Heidelberger, 1975; Gelboin et al., 1972). This review first describes structure-activity relationships for the mutagenicity of some epoxides and then outlines some findings on the metabolic control of the concentration of such epoxides by a number of enzymes.

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References

  • Arias, M., and Jakoby, W. B., 1976, “Glutathione: Metabolism and Function,” Raven Press, New York.

    Google Scholar 

  • Bend, J. R., Ben-Zvi, Z., Van Anda, H., Dansette, P. M., and Jerina, D. M., 1976, Hepatic and extrahepatic glutathione S-transferase activity toward several arene oxides and epoxides in the rat, in: “Polynuclear Aromatic Hydrocarbons,” R. Freudenthal and P. W. Jones, eds., Raven Press, New York.

    Google Scholar 

  • Bentley, P., and Oesch, F., 1975, Purification of rat liver epoxide hydratase to apparent homogeneity, FEBS Lett. 59: 291.

    CAS  PubMed  Google Scholar 

  • Bentley, P., Oesch, F., and Glatt, H. R., 1977, Dual role of epoxide hydratase in both activation and inactivation of benzo[a]pyrene, Arch. Toxicol. 39:65.

    Article  Google Scholar 

  • Bicker, M., Glatt, H. R., Platt, K. L., Avnir, D., Ittah, Y., Blum, J., and Oesch, F., 1979, Mutagenicity of phenanthrene and phenanthrene K-region derivates, Mutat. Res., 66: 337.

    Google Scholar 

  • Friedberg, T., Bentley, P., Stasiecki, P., Glatt, H. R., Raphael, D., and Oesch, F., 1979, The identification, solubilization, and characterization of microsome associated glutathione S-transferases, J. Biol. Chem. 254:12028.

    Google Scholar 

  • Gelboin, H. V., Kinoshita, N., and Wiebel, F., 1972, Microsomal hydroxylases: Induction and role in polycyclic hydrocarbon carcinogenesis and toxicity, Fed. Proc. 31:1298.

    Google Scholar 

  • Glatt, H. R., Vogel, K., Bentley, P., Sims, P., and Oesch, F., 1980, Effects of enzyme induction, pure epoxide hydrolase and dihydrodiol dehydrogenase on the mutagenicity of benz(a]anthracene, 7,12-dimethylbenz[a]anthracene and the twelve monomethylated benz[a]anthracenes in the Ames test, Cancer Res. submitted.

    Google Scholar 

  • Glatt, H. R., and Oesch, F., 1977, Inactivation of electrophilic metabolites by glutathione S-transferase and limitation of the system due to subcellular localization, Arch. Toxicol. 39:87.

    Article  Google Scholar 

  • Glatt, H. R., Vogel, K., Bentley, P., and Oesch, F., 1979a, Reduction of benzo[a]pyrene mutagenicity by dihydrodiol dehydrogenase, Nature 277: 319.

    CAS  PubMed  Google Scholar 

  • Glatt, H. R., Ohlsson, A., Agurell, S., and Oesch, F., 1979b, A1- Tetrahydrocannabinol and 1a,2a-epoxyhexahydrocannabinol: mutagenicity investigation in the Ames test, Mutat. Res., 66: 329.

    CAS  Google Scholar 

  • Heidelberger, C., 1975, Chemical carcinogenesis, Ann. Rev. Biochem. 44:79.

    Article  CAS  Google Scholar 

  • Hulbert, P. B., 1975, Carbonium ion as ultimate carcinogen of polycyclic aromatic hydrocarbons, Nature 256: 146.

    CAS  PubMed  Google Scholar 

  • Jerina, D. M., and Daly, J. W., 1974, Arene oxides: a new aspect of drug metabolism, Science 185: 573.

    CAS  PubMed  Google Scholar 

  • Jerina, D. M., and Lehr, R., 1977, The bay-region theory: a quantum mechanical approach to aromatic hydrocarbon-induced carcinogenicity, in: “Microsomes and Drug Oxidations,” V. Ullrich, I. Roots, A. G. Hildebrandt, R. W. Estabrook, and A. H. Conney, eds., Pergamon Press, Oxford.

    Google Scholar 

  • Jung, R., Beermann, D., Glatt, H. R., and Oesch, F., Mutagenicity of structurally related oxiranes: derivatives of benzene and its hydrogenated congeners, Mutat. Res. in press.

    Google Scholar 

  • Miller, E. C., and Miller, J. A., 1974, Biochemical mechanisms of chemical carcinogenesis, in: “Molecular Biology of Cancer,” H. Busch, ed., Academic Press, New York.

    Google Scholar 

  • Morgenstern, R., DePierre, J. W., and Ernster, L., 1979, Activation of microsomal glutathione S-transferase activity by sulfhydryl reagents, Biochem. Biophys. Res. Commun. 87:657.

    Article  CAS  Google Scholar 

  • Mumby, S. M., and Hammock, B. D., 1979, Substrate selectivity and stereochemistry of enzymatic epoxide hydration in the soluble fraction of mouse liver, Pestic. Biochem. Physiol. 11:275.

    Article  CAS  Google Scholar 

  • Nebert, D. W., Robinson, J. R., Niwa, A., Kumaki, K., and Poland, A. P., 1975, Genetic expression of aryl hydrocarbon hydroxylase activity in the mouse, J. Cell Physiol. 85:393.

    Article  CAS  Google Scholar 

  • Oesch, F., 1973, Mammalian epoxide hydrases: inducible enzymes catalyzing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds, Xenobiotica 3: 305.

    CAS  Google Scholar 

  • Oesch, F., 1974, Purification and specificity of a human microsomal epoxide hydratase, Biochem. J. 139:77.

    Article  CAS  Google Scholar 

  • Oesch, F., Kaubisch, N., Jerina, D. M., and Daly, J. W., 1971, Hepatic epoxide hydrase: structure-activity relationships for substrates and inhibitors, Biochemistry 10: 4858.

    CAS  PubMed  Google Scholar 

  • Oesch, F., Bentley, P., and Glatt, H. R., 1977a, Epoxide hydratase: purification to apparent homogeneity as a specific probe for the relative importance of epoxides among other reactive metabolites, in: “Biological Reactive Intermediates,” D. J. Jollow, J. J. Kocsis, R. Snyder, and H. Vainio, eds., Plenum Press, New York.

    Google Scholar 

  • Oesch, F., Glatt, H. R., and Schmassmann, H., 1977b, The apparent ubiquity of epoxide hydratase in rat organs, Biochem. Pharmacol. 26:603.

    Article  CAS  Google Scholar 

  • Oesch, F., and Golan, M., 1980, Specificity of mouse livercytosolic epoxide hydrolase for K-region epoxides derived from polycyclic aromatic hydrocarbons, Cancer Lett. 9: 169.

    CAS  PubMed  Google Scholar 

  • Sims, P., 1970, Qualitative and quantitative studies on the metabolism of a series of aromatic hydrocarbons by rat-liver preparations, Biochem. Pharmacol. 19:795.

    Article  CAS  Google Scholar 

  • Sims, P., and Grover, P. L., 1974, Epoxides in polycyclic aromatic hydrocarbon metabolism and carcinogenesis, Adv. Cancer Res. 20:165.

    Google Scholar 

  • Sims, P., Grover, P. L., Swaisland, A., Pal, K., and Hewer, A., 1974, Metabolic activation of benzo[a]pyrene proceeds by a diol-epoxide, Nature 252: 326.

    CAS  PubMed  Google Scholar 

  • Stasiecki, P., Oesch, F., Bruder, G., Jarasch, E.-D., and Franke, W. W., 1980, Distribution of enzymes involved in metabolism of polycyclic aromatic hydrocarbons among rat liver endomembranes and plasma membranes, Eur. J. Cell Biol. 21:79.

    Google Scholar 

  • Vogel, E., Beermann, D., Balci, E., and Altenbach, H.-J., 1976, Oxepin-2,7-dialdehyd, Tetrahedron Lett. 1167.

    Google Scholar 

  • Vogel, E., and Günther, H., 1976, Benzoloxid-Oxepin-Valenztautomerie, Angew. Chem. 79:429.

    Article  Google Scholar 

  • Vogel, K., Bentley, P., Platt, K.-L., and Oesch, F., 1980, Rat liver cytoplasmic dihydrodiol dehydrogenase: purification to apparent homogeneity and properties, J. Biol. Chem. in press.

    Google Scholar 

  • Walker, C. H., Bentley, P., and Oesch, F., 1977, Phylogenetic distribution of epoxide hydratase in different vertebrate species, strains and tissues measured using three substrates, Biochim. Biophys. Acta 539:427.

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Institute of Pharmacology, University of Mainz, D-6500, Mainz, Germany

    Franz Oesch

Authors
  1. Franz Oesch
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Editor information

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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Oesch, F. (1982). Fate of Epdxides. 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_3

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  • DOI: https://doi.org/10.1007/978-1-4757-0674-1_3

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4757-0676-5

  • Online ISBN: 978-1-4757-0674-1

  • eBook Packages: Springer Book Archive

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