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Induction of Cytochrome P450 Enzymes That Metabolize Xenobiotics

  • James P. WhitlockJr.
  • Michael S. Denison
Chapter

Abstract

One of the many interesting aspects of the cytochrome P450 enzymes is that some are inducible; that is, following exposure of the cell to an inducing chemical, enzyme activity increases, in some cases by orders of magnitude. The induction phenomena were first recognized because they produced alterations in pharmacological responses to drugs or other xenobiotics. For example, animals chronically exposed to barbiturates become “tolerant” to the hypnotic effects of these drugs, because they induce the cytochrome P450 enzymes responsible for their own metabolism.1 Similarly, the induction of cytochrome P450 enzymes reduced the incidence of neoplasia in animals exposed to chemical carcinogens2 Such examples illustrate two interesting points. First, inducers are often substrates for the induced enzymes; thus, enzyme activity increases only as needed. Second, enzyme induction usually enhances detoxification, particularly when low to moderate concentrations of substrate are present; thus, under most conditions, induction is a protective mechanism, whereby the cell can detoxify lipophilic compounds that might otherwise accumulate. Both characteristics are likely to facilitate the survival of the cell in a potentially toxic chemical environment.

Keywords

Cytochrome P450 Enzyme Induction Mechanism Cytochrome P450 Gene Aryl Hydrocarbon Hydroxylase Aryl Hydrocarbon Hydroxylase Activity 
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

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • James P. WhitlockJr.
    • 1
  • Michael S. Denison
    • 2
  1. 1.Department of Molecular PharmacologyStanford University School of MedicineStanfordUSA
  2. 2.Department of Environmental ToxicologyUniversity of California, DavisDavisUSA

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