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Modifiers of Cytochrome(s) P450

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Cancer Chemoprevention

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Cytochromes P450 (CYPs) belong to a superfamily of enzymes that have different, but overlapping, substrate specificities and tissue distribution. The highest concentration of CYPs is in the liver endoplasmic reticulum, but P450 is found in most other tissues of the body. CYPs are heme-containing enzymes that can either detoxify or bioactivate xenobiotics (foreign chemicals). The following seven types of reactions are catalyzed by CYPs: i) hydroxylation of an aliphatic or aromatic carbon; ii) epoxidation of a double bond; iii) heteroatom (S-, N-, and I-) oxygenation and N-hydroxylation; iv) heteroatom (O-, S-, and N-) dealkylation; v) oxidative group transfer; vi) cleavage of esters; and vii) dehydrogenation (1). In humans, the predominant isoform of P450 in the liver is CYP1A2. Other human liver P450s include CYP 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 (reviewed in ref. 1). CYP 1 A 1 is expressed in extrahepatic sites including human lung, the intestines, the skin, lymphocytes, and the placenta. Human CYP 1 B 1 catalyzes the activation of a number of diverse pro-carcinogens (2), and is expressed in a variety of extra-hepatic sites, including steroid-responsive and steroidogenic tissues (3–5).

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Authors
  1. John DiGiovanni PhD
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  2. Heather E. Kleiner PhD
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  1. National Institutes of Health, Rockville, MD, USA

    Gary J. Kelloff MD  & Ernest T. Hawk MD, MPH  & 

  2. CCS Associates, Mountain View, CA, USA

    Caroline C. Sigman PhD

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DiGiovanni, J., Kleiner, H.E. (2004). Modifiers of Cytochrome(s) P450. In: Kelloff, G.J., Hawk, E.T., Sigman, C.C. (eds) Cancer Chemoprevention. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-767-3_4

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  • DOI: https://doi.org/10.1007/978-1-59259-767-3_4

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