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Mechanisms of Cytochrome P450-Mediated Formation of Pneumotoxic Electrophiles

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Book cover Biological Reactive Intermediates V

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 387))

Abstract

Toxicity to lung tissues from systemically circulated chemicals is largely mediated by the bioactivation of these agents by cytochrome P450 enzymes. The toxicity to lung cells is generally caused by reactive electrophiles that are formed as a result of oxygenation or desaturation of the starting xenobiotic molecule. Examples of the reactive intermediates include epoxides, quinone methides, methylene imines, and acyl halides. Selective lung toxicants include naphthalene, butylated hydroxytoluene, 4-ipomeanol, and 3-methylindole (3MI). Examples of pneumotoxic electrophiles that are formed by P450-mediated oxidation of the parent molecules are shown in Figure 1. Also shown are the P450 enzymes that have been proposed to be responsible for the bioactivation of each compound.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, 84112, USA

    Garold S. Yost

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  1. Garold S. Yost
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Editors and Affiliations

  1. Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey, USA

    Robert Snyder  & Charlotte M. Witmer  & 

  2. University of Arizona, Tuscon, Arizona, USA

    I. Glenn Sipes

  3. Medical University of South Carolina, Charleston, South Carolina, USA

    David J. Jollow

  4. University of Texas, Austin, Texas, USA

    Terrence J. Monks

  5. Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    James J. Kocsis  & George F. Kalf  & 

  6. GSF Institute of Toxicology, Technical University, Munich, Germany

    Helmut Greim

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© 1996 Springer Science+Business Media New York

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Yost, G.S. (1996). Mechanisms of Cytochrome P450-Mediated Formation of Pneumotoxic Electrophiles. In: Snyder, R., et al. Biological Reactive Intermediates V. Advances in Experimental Medicine and Biology, vol 387. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9480-9_30

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  • DOI: https://doi.org/10.1007/978-1-4757-9480-9_30

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9482-3

  • Online ISBN: 978-1-4757-9480-9

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