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Monoclonal Antibody-Directed Analysis of Cytochrome P-450

  • Fred K. Friedman
  • Sang S. Park
  • Byung J. Song
  • Kuo C. Cheng
  • Harry V. Gelboin
  • T. Fujino
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)

Abstract

The cytochromes P-450 metabolize a diverse array of xenobiotic and endobiotic compounds, including carcinogens, drugs, and steroids (1-3). The different isozymes differ in their substrate and product specificities and reactivities. The types and amounts of isozymes in a tissue therefore regulate the metabolic conversion of substrates to products. Progress in understanding the role of individual P-450s in metabolism of specific substrates, and in relating P-450 phenotype to individual differences in sensitivity to drugs and carcinogens, has been hindered by the multiplicity of the P-450s. The approach we have taken to the multiplicity problem is to prepare and use monoclonal antibodies (MAbs) as specific probes to individual and epitope-specific classes of P-450s (4–6).

Keywords

Aryl Hydrocarbon Hydroxylase Reaction Phenotyping Kidney Microsome Aryl Hydrocarbon Hydroxylase Activity Aryl Hydrocarbon Hydroxylase Inducer 
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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References

  1. 1.
    A. Y. H. Lu, and S. B. West, Multiplicity of mammalian microsomal cytochromes P-450, Pharmacol. Rev., 31: 277 (1980).Google Scholar
  2. 2.
    H. V. Gelboin, Benzo[a]pyrene metabolism, activation, and carcinogenesis: Role of mixed-function oxidases and related enzymes, Physiol. Rev., 60: 1107 (1980).Google Scholar
  3. 3.
    R. Sato, and R. Kato, “Microsomes, Drug Oxidations, and Drug Toxicity,” Scientific Societies Press, Japan (1982).Google Scholar
  4. 4.
    S. S. Park, S. J. Cha, H. Miller, A. V. Persson, M. J. Coon, and H. V. Gelboin, Monoclonal antibodies to rabbit liver cytochrome P-450 LM2 and P-450 LM4, Mol. Pharmacol., 21: 248 (1981).Google Scholar
  5. 5.
    S. S. Park, T. Fujino, D. West, F. P. Guengerich, and H. V. Gelboin, Monoclonal antibodies that inhibit enzyme activity of 3-methylcholanthrene induced cytochrome P-450, Cancer Res., 42: 1798 (1982).PubMedGoogle Scholar
  6. 6.
    S. S. Park, T. Fujino, H. Miller, F. P. Guengerich, and H. V. Gelboin, Monoclonal antibodies to phenobarbital-induced rat liver cytochrome P-450, Biochem. Pharmacol., 33: 2071 (1984).Google Scholar
  7. 7.
    B. J. Song, H. V. Gelboin, S. S. Park, F. K. Friedman, Epitoperelatedness and phenotyping of hepatic cytochrome P-450 with monoclonal antibodies, Biochem. J., (in press).Google Scholar
  8. 8.
    F. K. Friedman, R. C. Robinson, S. S. Park, and H. V. Gelboin, Monoclonal antibody-directed immunopurification and identification of rat liver cytochromes P-450, Biochem. Biophys. Res. Commun., 116: 859 (1983).CrossRefGoogle Scholar
  9. 9.
    K. C. Cheng, H. V. Gelboin, B. J. Song, S. S. Park, and F. K. Friedman, Detection and purification of cytochromes P-450 in animal tissues with monoclonal antibodies, J. Biol. Chem., 259: 12279 (1984).PubMedGoogle Scholar
  10. 10.
    K. C. Cheng, H. C. Krutzsch, S. S. Park, P. H. Granthan, H. V. Gelboin, and F. K. Friedman, Amino-terminal sequence analysis of six cytochrome P-450 isozymes purified by monoclonal antibody directed immunopurification, Biochem. Biophys. Res. Commun., 123: 1201 (1984).CrossRefGoogle Scholar
  11. 11.
    K. C. Cheng, H. V. Gelboin, S. S. Park, and F. K. Friedman, Structural relatedness of six monoclonal antibody immunopurified cytochromes P-450, (submitted).Google Scholar
  12. 12.
    Y. Yabusaki, M. Shimizu, H. Murakami, K. Nakamura, K. Oeda, and H. Ohkawa, Nucleotide sequence of a full-length cDNA coding for 3-methylcholanthrene-induced rat liver cytochrome P-450 MC. Nucleic Acid Res., 12: 2929 (1984).PubMedCrossRefGoogle Scholar
  13. 13.
    S. Kimura, F. J. Gonzalez, and D. W. Nebert, The murine Ah locus: comparison of the complete cytochrome P1–450 and P3–450 cDNA nucleotide and amino acid sequences. J. Biol. Chem., 259: 10705 (1984).PubMedGoogle Scholar
  14. 14.
    L. H. Botelho, D. E. Ryan, P-M. Yuan, R. Kutny, J. E. Shirley, and W. Levin, Amino-terminal and carboxy-terminal sequence of hepatic microsomal cytochrome P-450d, a unique hemoprotein from rats treated with isosafrole, Biochemistry, 21: 1152 (1982).PubMedCrossRefGoogle Scholar
  15. 15.
    T. Fujino, D. West, S. S. Park, and H. V. Gelboin, Monoclonal antibody-directed phenotyping of cytochrome P-450-dependent aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase in mammalian tissues, J. Biol. Chem., 259: 9044 (1984).PubMedGoogle Scholar
  16. 16.
    T. Fujino, S. S. Park, D. West, and H. V. Gelboin, Phenotyping of cytochrome P-450 in human tissues with monoclonal antibodies, Proc. Natl. Acad. Sci. USA, 70: 3682 (1982).CrossRefGoogle Scholar
  17. 17.
    T. Fujino, K. Gottlieb, D. K. Manchester, S. S. Park, D. West, H. L. Gurtoo, and H. V. Gelboin, Monoclonal antibody phenotyping of inter-individual differences in cytochrome P-450 dependent reactions of single and twin human placenta. Cancer Res., 44: 3916 (1984).PubMedGoogle Scholar
  18. 18.
    H. V. Gelboin, and F. K. Friedman, Monoclonal antibodies for studies on xenobiotic and endobiotic metabolism: cytochromes P-450 as paradigm. Biochem. Pharmacol., 34: 2225 (1985).PubMedCrossRefGoogle Scholar
  19. 19.
    B. J. Song, T. Fujino, S. S. Park, F. K. Friedman, and H. V. Gelboin, Monoclonal antibody-directed radioimmunoassay of specific cytochromes P-450, J. Biol. Chem., 259: 1394 (1984).PubMedGoogle Scholar
  20. 20.
    H. V. Gelboin, Carcinogens, drugs and cytochromes P-450, N. Engl. J. Med., 309: 105 (1983).PubMedCrossRefGoogle Scholar
  21. 21.
    B. J. Song, H. V. Gelboin, S. S. Park, G. Tsokos, and F. K. Friedman, Monoclonal antibody-directed radioimmunoassay detects cytochrome P-450 in human placenta and lymphocytes, Science, 228: 490 (1985).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Fred K. Friedman
    • 1
  • Sang S. Park
    • 1
  • Byung J. Song
    • 1
  • Kuo C. Cheng
    • 1
  • Harry V. Gelboin
    • 1
  • T. Fujino
    • 1
  1. 1.National Cancer InstituteNational Institutes of HealthBethesdaUSA

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