Effects of 1-ethynylpyrene and related inhibitors of P450 isozymes upon benzo[a]pyrene metabolism by liver microsomes

Chem Biol Interact. 1990;76(2):181-92. doi: 10.1016/0009-2797(90)90087-4.

Abstract

The effects of three aryl acetylenes, 1-ethynylpyrene (EP), 2-ethynylnaphthalene (EN) and 3-ethynylperylene (EPE), upon the metabolism of benzo[a]pyrene (BaP) by microsomes isolated from rat liver were investigated. These aryl acetylenes all inhibited the total metabolism of BaP. Formation of BaP 7,8-dihydrodiol and BaP tetrol products by microsomal preparations from rats that had been pretreated with 3-methylcholanthrene (3MC) were preferentially inhibited. The effects of EP upon the metabolism of BaP 7,8-dihydrodiol by microsomes from rat liver were also studied. This aryl acetylene strongly inhibited the formation of BaP tetrols from BaP 7,8-dihydrodiol by liver microsomes both from untreated rats and from rats pretreated with 3MC, but enhanced the conversion of the BaP dihydrodiol into other metabolites.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzo(a)pyrene / chemistry
  • Benzo(a)pyrene / metabolism*
  • Cytochrome P-450 Enzyme Inhibitors*
  • Isoenzymes / antagonists & inhibitors*
  • Male
  • Methylcholanthrene
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / metabolism
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology*
  • Perylene / analogs & derivatives*
  • Perylene / chemistry
  • Perylene / pharmacology
  • Pyrenes / chemistry
  • Pyrenes / pharmacology*
  • Rats
  • Rats, Inbred Strains

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Isoenzymes
  • Naphthalenes
  • Pyrenes
  • 3-ethynylperylene
  • 2-ethynylnaphthalene
  • Benzo(a)pyrene
  • 1-ethynylpyrene
  • Methylcholanthrene
  • Perylene