Metabolic and Structural Requirements for the Carcinogenic Potencies of Unsubstituted and Methyl-Substituted Polycyclic Aromatic Hydrocarbons

  • Shen K. Yang
  • Ming W. Chou
  • Peter P. Fu
Part of the The Jerusalem Symposia on Quantum Chemistry and Biochemistry book series (JSQC, volume 13)

Abstract

Extensive metabolism studies of many non-K-region dihydro-diols of unsubstituted and methyl-substituted polycyclic aromatic hydrocarbons (PAHs) by mammalian drug-metabolizing enzymes indicate that the extent of formation of vicinal dihydrodiol-epoxides is determined by the conformations and geometric location of the adjacent double bond of the dihydrodiol precursors. Unsubstituted PAH dihydrodiols with one (in the case of cis-dihydrodiols) or both (in the case of trans-dihydrodiols) of the hydroxyl groups preferentially in quasi- equatorial conformations can be further metabolized to the vicinal di- hydrodiol-epoxides. The trans-dihydrodiols with both of the hydroxyl groups preferentially or exclusively in the quasi-diaxial. conformations can also be enzymatically epoxidized to form vicinal dihydrodiol-epox- ides, but the extent of these formations is highly dependent on the geometric location of the adjacent double bond of the dihydrodiols. Quasi-diaxial trans-dihydrodiols with an adjacent double bond at the bay-regions are not or minimally metabolized to the vicinal dihydrodiol-epoxides. A methyl substituent at the hydroxylated carbons or at the adjacent double bonds of the quasi-diequatorial trans-dihydrodiols can substantially or completely inhibit the vicinal dihydrodiol-epoxide formations. These findings, along with the bay-region theory, provide the molecular basis for the observed carcinogenic potencies of many bay-region containing unsubstituted and methyl-substituted PAHs.

Keywords

Hydrocarbon Adduct Peri Pyrene Anthracene 

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Copyright information

© D. Reidel Publishing Company 1980

Authors and Affiliations

  • Shen K. Yang
    • 1
  • Ming W. Chou
    • 1
  • Peter P. Fu
    • 2
  1. 1.Department of Pharmacology, School of MedicineUniformed Services University of the Health SciencesBethesdaUSA
  2. 2.National Center for Toxicological ResearchJeffersonUSA

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