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Studies on the Spin State of 3-Methylcholanthrene Induced Cytochrome P-450 from Rat Liver

  • J. O. Stern
  • E. Peisach
  • J. Peisach
  • W. E. Blumberg
  • A. Y. H. Lu
  • S. West
  • D. Ryan
  • W. Levin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 58)

Summary

The time course of induction of rat liver microsomal cytochrome P-450 by the polycyclic hydrocarbon 3-methylcholanthrene was followed by measuring the specific content of cytochrome P-450, benzpyrene hydroxylase activity, and the percent of cytochrome P-450 existing as the high-spin form (g = 7.9, 3.7 and 1.7) as determined by low temperature EPR spectroscopy. Significant increases in benzpyrene hydroxylase, cytochrome P-450 and high-spin ferric hemoprotein are seen twenty-four hours following 3-methylcholanthrene treatment. Administration of DL-ethionine prior to 3-methylcholanthrene treatment effectively blocks any increase in benzpyrene hydroxylase and cytochrome P-450 but not the increase in the levels of the high-spin species of the hemoprotein normally seen following 3-methylcholanthrene induction. In addition, partially purified cytochrome P-450 can be isolated from liver microsomes of 3-methylcholanthrene treated rats as a low-spin ferric hemoprotein containing essentially no high-spin species (<1%). This partially purified hemoprotein has the same substrate specificity as the microsomes from which it was derived. It is therefore concluded that the appearance of the high-spin form of cytochrome P-450, as quantitated by EPR, does not correlate with the induction of cytochrome P-450 and benzpyrene hydroxylase activity by 3-methylcholanthrene.

Keywords

Polycyclic Hydrocarbon Microsomal Pellet Public Health Service Research Total Cytochrome Liver Microsomal Cytochrome 
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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Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • J. O. Stern
    • 1
    • 2
    • 3
    • 4
  • E. Peisach
    • 1
    • 2
    • 3
    • 4
  • J. Peisach
    • 1
    • 2
    • 3
    • 4
  • W. E. Blumberg
    • 1
    • 2
    • 3
    • 4
  • A. Y. H. Lu
    • 1
    • 2
    • 3
    • 4
  • S. West
    • 1
    • 2
    • 3
    • 4
  • D. Ryan
    • 1
    • 2
    • 3
    • 4
  • W. Levin
    • 1
    • 2
    • 3
    • 4
  1. 1.Departments of Pharmacology and Molecular BiologyAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  2. 2.Institute for Developmental StudiesNew York UniversityNew YorkUSA
  3. 3.Bell Laboratories, Inc.Murray HillUSA
  4. 4.Department of Biochemistry and Drug MetabolismHoffman-LaRoche, Inc.NutleyUSA

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