Skip to main content

Benzene Metabolism by Two Purified, Reconstituted Rat Hepatic Mixed Function Oxidase Systems

  • Chapter
Biological Reactive Intermediates IV

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 283))

Abstract

Benzene, a bone marrow depressant, requires metabolism in order to exert its hematopoetic toxicity (Snyder et al., 1980). In mammals, this metabolism ccurs primarily in the liver and is catalyzed by the cytochrome P-450 containing mixed function oxidase (MFO) system (Gonasun et al., 1973). Post and Snyder (1983) demonstrated that rat liver microsomes contain at least two, distinct MFO activities which can metabolize benzene. One is induced by phenobarbital (PB) pretreatment and displays a Km value greater than 10mM; the other is induced by benzene pretreatment and displays a Km value equal to approximately 0.1mM. PB pretreatment results in the induction of cytochrome P450IIB1 (Ryan et al., 1979), while benzene pretreatment appears to induce cytochrome P450IIE1 (Ingelman-Sundberg and Johansson, 1984). Koop et al. (1989) demonstrated that P45011E1, purified from rabbit liver microsomes, is an effective benzene hydroxylase. In this study, we have examined benzene metabolism by two purified, reconstituted rat hepatic MFO systems containing either cytochrome P450IIB1 or P450IIE1.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Dignam, J.D. and Stroebel, H.W. (1975). Preparation of homogenous NADPH-cytochrome P-450 reductase from rat liver. Biochem. Biophys. Res. Commun. 63, 845–852.

    Article  CAS  PubMed  Google Scholar 

  • Gonasun, L., Witmer, C., Kocsis, J.J. and Snyder, R. (1973). Benzene metabolism in mouse liover microsomes. Toxicol. Appl. Pharmacol. 26, 398–406.

    Article  CAS  PubMed  Google Scholar 

  • Ingelman-Sundberg, M., and Johansson, I. (1984). Mechanisms of hydroxyl radical formation and ethanol oxidation by ethanol-inducible and other forms of rabbit liver microsomal cytochromes P-450. J. Biol. Chem. 259, 6447–6458.

    CAS  PubMed  Google Scholar 

  • Koop, D.R., Laethem, C.L. and Schnier, G.G. (1989). Identification of ethanol-inducible P450 isozyme 3a (P450IIE1) as a benzene and phenol hydroxylase. Toxicol. Appl. Pharmacol. 98, 278–288.

    Article  CAS  PubMed  Google Scholar 

  • Lu, A.Y.H. and Levin, W. (1972). Partial purification of cytochromes P-450 and P-448 from rat liver microsomes. Biochem. Biophys. Res. Commun. 46, 1334–1339.

    Article  CAS  PubMed  Google Scholar 

  • Post, G.B. and Snyder, R. (1983). Effects of enzyme induction on microsomal benzene metabolism. J. Toxicol. Environ. Health. 11, 811–825.

    Article  CAS  PubMed  Google Scholar 

  • Ryan, D.E., Ramanathan, L., lida, S., Thomas, P.E., Haniu, M., Shively, J.E., Lieber, C.S. and Levin, W. (1985). Characterization of a major form of rat hepatic microsomal cytochrome P-450 induced by isoniazid. J. Biol. Chem. 260, 6385–6393.

    CAS  PubMed  Google Scholar 

  • Ryan, D.E., Thomas, P.E., Korzeniowski, D. and Levin, W. (1979). Separation and characterization of highly purified forms of liver microsomal cytochrome P-450 from rats treated with polychlorinated biphenyls, phenobarbital, and 3- methylcholanthrene. J. Biol. Chem. 254, 1365–1374.

    CAS  PubMed  Google Scholar 

  • Ryan, D.E., Thomas, P.E. and Levin, W. (1982). Purification and characterization of a minor form of hepatic microsomal cytochrome P-450 from rats treated with polychlorinated biphenyls. Arch. Biochem. Biophys. 216, 272–288.

    Article  CAS  PubMed  Google Scholar 

  • Snyder, R., Sammett, D., Witmer, C., Kocsis, J.J. and Snyder, R. (1980). An overview of the problem of benzene toxicity and some recent data on the relationship of benzene metabolism to benzene toxicity. In: Genotoxic Effects of Airborne Agents. Tice, R.R., Costa, D.L. and Scheich, K.M. (eds.) Plenum Press, New York.

    Google Scholar 

  • Tamburini, P.P., White, R.E. and Schenkman, J.B. (1985). Chemical characterization of protein-protein interactions between cytochrome P-450 and cytochrome b5. J. Biol. Chem. 260, 4007–4015.

    CAS  PubMed  Google Scholar 

  • Yasukochi, Y. and Masters, B.S.S. (1976). Some properties of a detergent-solubilized NADPH-cytochrome e (cytochrome P-450) reductase purified by biospecific affinity chromatography. J. Biol. Chem. 251, 5337–5344.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Plenum Press, New York

About this chapter

Cite this chapter

Chepiga, T.A., Yang, C.S., Snyder, R. (1991). Benzene Metabolism by Two Purified, Reconstituted Rat Hepatic Mixed Function Oxidase Systems. In: Witmer, C.M., Snyder, R.R., Jollow, D.J., Kalf, G.F., Kocsis, J.J., Sipes, I.G. (eds) Biological Reactive Intermediates IV. Advances in Experimental Medicine and Biology, vol 283. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5877-0_28

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-5877-0_28

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5879-4

  • Online ISBN: 978-1-4684-5877-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics