Advertisement

Covalent Binding of Metabolically Activated Hydrocarbons to Specific Microsomal Proteins

  • Bengt Jergil
  • Cecilia Schelin
  • Anders Tunek
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

Many toxic and/or carcinogenic compounds become covalently bound to DNA, RNA, and proteins of target cells (Jollow et al., 1977). These compounds often have to be metabolised to chemically reactive forms before they can bind to macromolecules (Miller and Miller, 1972; Gillette et al., 1974). Usually this metabolic activation is catalysed by the mixed-function oxidase system located principally in the endoplasmic reticulum.

Keywords

Liver Microsome Covalent Binding Microsomal Protein Carcinogenic Compound Liver Microsomal Protein 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gillette, J.R., Mitchell, J.R. and Brodie, B.B.,1974, Biochemical mechanisms of drug toxicity, Annu. Rev. Pharmacol., 14: 271.CrossRefGoogle Scholar
  2. Heidelberger, C., 1975, Chemical carcinogenesis, Annu. Rev. Biochem., 44: 79.Google Scholar
  3. Jerina, D.M., Ziffer, H., and Daly, J. W., 1970, The role of the arene oxide-oxepin system in the metabolism of aromatic substrates. IV. Stereochemical considerations of dihydrodiol formation and dehydrogenation, J. Am. Chem. Soc., 92: 1056.CrossRefGoogle Scholar
  4. Jerina, D.M. and Daly, J.W., 1974, Arene oxides: A new aspect of drug metabolism, Science, 185: 573.PubMedCrossRefGoogle Scholar
  5. Jollow, D.J., Kocsis, J.J., Snyder, R., and Vainio, H. (eds.), 1977, “Biological Reactive Intermediates. Formation, Toxicity and Inactivation”, Plenum Press, New York.Google Scholar
  6. Ketterer, B., 1980, Interactions between carcinogens and proteins, Br. Med. Bull., 36: 71.PubMedGoogle Scholar
  7. Miller, E.C. and Miller, J.A., 1972, Biochemical mechanisms of chemical carcinogenesis, in “Molecular Biology of Cancer”, H. Busch, ed., Academic Press, New York.Google Scholar
  8. Schelin, C., Tunek, A., Jernström, B., and Jergil, B., 1980, Irreversible binding of isolated benzo(a)pyrene metabolites to specific rat liver microsomal proteins, Mol. Pharmacol., in press.Google Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. Tunek, A., Schelin, C., and Jergil, B., 1979, Microsomal target proteins of metabolically activated aromatic hydrocarbons, Chem.-Biol. Interact., 27: 133.PubMedCrossRefGoogle Scholar
  11. Tunek, A., Platt, K.L., Przybylski, M., and Oesch, F., Multistep metabolic activation of benzene. Effect of superoxide dismutase on covalent binding to microsomal macromolecules, and identification of glutatione conjugates using high pressure liquid chromatography and field desorption mass spectrometry, Chem.-Biol. Interact., in press.Google Scholar
  12. Uehleke, H., 1973, The model system of microsomal drug activation and covalent binding to endoplasmic proteins, Proc. Eur. Soc. Study Drug. Toxic., 15: 119.Google Scholar
  13. Weisburger, E.K., 1978, Mechanisms of chemical carcinogenesis, Annu. Rev. Pharmacol. Toxicol., 18: 395.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Bengt Jergil
    • 1
  • Cecilia Schelin
    • 1
  • Anders Tunek
    • 2
  1. 1.Biochemistry 1, Chemical CentreUniversity of LundLund 7Sweden
  2. 2.Department of Environmental HealthUniversity of LundLundSweden

Personalised recommendations