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Symposium Presentation

Regulation of Cytochrome P-450 and Carcinogenesis: Peroxisome Proliferator-Activated Receptor and Dioxin Receptor

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Hormonal Carcinogenesis II

  • 61 Accesses

Abstract

Chemical carcinogenesis often involves metabolic activation of precursor compounds to reactive species which may initiate the carcinogenic process by interacting with the genetic material, leading to formation of DNA-adducts and other chemical insults. A key enzyme in this scenario is cytochrome P-450, which can carry out a multitude of chemical reactions whereby both xenobiotics and sometimes endogenous compounds may be transformed into highly reactive metabolites. Alternatively, the reactions may lead to the generation of highly reactive side products, e.g., free radicals. Accordingly, the levels of different isoforms of cytochrome P-450 in various tissues are enormously important in determining the extent of these activation processes in the organism. Therefore, regulation of cytochrome P-450 is a most significant issue in the elucidation of chemical carcinogenesis. Often, hormones are important regulators of cytochrome P-450; thus, hormonal carcinogenesis may involve hormonal regulation of cytochrome P-450. We have chosen to illustrate regulation of cytochrome P-450 with two examples. The first is the peroxisome proliferator-activated receptor (PPAR), which regulates P-450 of the 4A type and for which involvement in liver carcinogenesis has been claimed. We and others have discovered that PPAR-regulated genes may be expressed by dehydroepiandrosterone sulphate; this paper addresses possible mechanisms involved. Secondly, we describe certain aspects of Ah (dioxin)-receptor activation, an important transcription factor for development of the immune system and liver (1). It has been claimed that the dioxin receptor is involved in chemical carcinogenesis; we will show that common air pollutants may be important in activating the receptor and thus causing an increased transcription of cytochrome P-450.

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Authors
  1. Carol D. Banner
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  2. Joseph J. Rafter
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  3. Jan-Åke Gustafsson
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Editor information

Editors and Affiliations

  1. Division of Etiology and Prevention of Hormonal Cancers, Hormonal Carcinogenesis Laboratory, University of Kansas Cancer Center, Kansas City, Kansas, USA

    J. Jonathan Li Ph.D. (Professor of Pharmacology, Toxicology, and Therapeutics, Director) (Professor of Pharmacology, Toxicology, and Therapeutics, Director)

  2. Hormonal Carcinogenesis Laboratory, University of Kansas Cancer Center, Kansas City, Kansas, USA

    Sara Antonia Li Ph.D. (Associate Professor of Pharmacology, Toxicology, and Therapeutics) (Associate Professor of Pharmacology, Toxicology, and Therapeutics)

  3. Department of Medical Nutrition, Center for Biotechnology, NOVUM, Huddinge University Hospital, Huddinge, Sweden

    Jan-Åke Gustafsson M.D., Ph.D. (Professor and Chairman, Director) (Professor and Chairman, Director)

  4. Department of Molecular and Cell Biology, Cancer Research Center, University of California, Berkeley, California, USA

    Satyabrata Nandi Ph.D. (Professor of Cell and Development Biology) (Professor of Cell and Development Biology)

  5. Division of Cancer Etiology, Chemical and Physical Carcinogenesis Program, National Cancer Institute, Rockville, Maryland, USA

    Lea I. Sekely Ph.D. (Program Director) (Program Director)

  6. University of Kansas Medical Center, Kansas City, Kansas, USA

    J. Jonathan Li Ph.D. (Professor of Pharmacology, Toxicology, and Therapeutics, Director) & Sara Antonia Li Ph.D. (Associate Professor of Pharmacology, Toxicology, and Therapeutics) (Professor of Pharmacology, Toxicology, and Therapeutics, Director) &  (Associate Professor of Pharmacology, Toxicology, and Therapeutics)

  7. National Institutes of Health, Rockville, Maryland, USA

    Lea I. Sekely Ph.D. (Program Director) (Program Director)

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© 1996 Springer-Verlag New York, Inc.

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Banner, C.D., Rafter, J.J., Gustafsson, JÅ. (1996). Symposium Presentation. In: Li, J.J., Li, S.A., Gustafsson, JÅ., Nandi, S., Sekely, L.I. (eds) Hormonal Carcinogenesis II. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2332-0_4

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  • DOI: https://doi.org/10.1007/978-1-4612-2332-0_4

  • Publisher Name: Springer, New York, NY

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