Mechanisms of Cytochrome P450-Mediated Formation of Pneumotoxic Electrophiles

  • Garold S. Yost
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)


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.


Reactive Intermediate Cytochrome P450 Enzyme Hydrogen Atom Abstraction Quinone Methide Methyl Oxidation 
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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Garold S. Yost
    • 1
  1. 1.Department of Pharmacology and ToxicologyUniversity of UtahSalt Lake CityUSA

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