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

  • Thomas A. Chepiga
  • Chung S. Yang
  • Robert Snyder
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


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.


Mixed Function Oxidase Lower Substrate Concentration Mixed Function Oxidase System Hepatic Microsomal Cytochrome Liver Microsomal Cytochrome 
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  1. 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.CrossRefPubMedGoogle Scholar
  2. Gonasun, L., Witmer, C., Kocsis, J.J. and Snyder, R. (1973). Benzene metabolism in mouse liover microsomes. Toxicol. Appl. Pharmacol. 26, 398–406.CrossRefPubMedGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. Post, G.B. and Snyder, R. (1983). Effects of enzyme induction on microsomal benzene metabolism. J. Toxicol. Environ. Health. 11, 811–825.CrossRefPubMedGoogle Scholar
  7. 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.PubMedGoogle Scholar
  8. 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.PubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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
  11. 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.PubMedGoogle Scholar
  12. 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.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Thomas A. Chepiga
    • 1
  • Chung S. Yang
    • 2
  • Robert Snyder
    • 1
  1. 1.Joint Graduate Program in ToxicologyRutgers University/Robert Wood Johnson Medical SchoolPiscatawayUSA
  2. 2.Department of Chemical Biology and Pharmacognosy, College of PharmacyRutgers University/Robert Wood Johnson Medical SchoolPiscatawayUSA

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