Induction of rat hepatic cytochromes P-450 by environmental nitropolycyclic aromatic hydrocarbons

Biochem Pharmacol. 1987 Aug 1;36(15):2449-54. doi: 10.1016/0006-2952(87)90515-6.

Abstract

Nitrated polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that result from various incomplete combustion processes. We have examined the activity of hepatic microsomal enzymes in rats pretreated with a series of environmentally occurring nitrated PAHs including: 1- and 4-nitropyrene, 1,3-, 1,6- and 1,8-dinitropyrene, 6-nitrochrysene, 7-nitrobenz[a]anthracene, 3-nitrofluoranthene, and 1-, 3-, and 6-nitrobenzo[a]pyrene. None of the compounds increased the cytochrome P-450 content more than 2-fold. 1,8-Dinitropyrene, 6-nitrochrysene, and 1- and 3-nitrobenzo[a]pyrene significantly increased arylhydrocarbon hydroxylase activity 2- to 8-fold higher than solvent-treated controls. The induction of 7-ethoxycoumarin O-deethylase activity paralleled that found with arylhydrocarbon hydroxylase. The maximum induction of aminopyrine N-demethylase was only 1.5-fold, and none of the nitrated PAHs caused significant increases in epoxide hydrase or NADPH-cytochrome c reductase. 1-Nitropyrene reductase activity was induced by each of the compounds with the exception of 6-nitrobenzo[a]pyrene. The greatest increase was caused by 1-nitrobenzo[a]pyrene followed by 1,3-dinitropyrene, 3-nitrobenzo[a]pyrene and 6-nitrochrysene. These data suggest that nitrated PAHs may potentiate the effects of subsequent exposures to various chemical carcinogens.

MeSH terms

  • 7-Alkoxycoumarin O-Dealkylase
  • Air Pollutants / pharmacology*
  • Aminopyrine N-Demethylase / biosynthesis
  • Animals
  • Aryl Hydrocarbon Hydroxylases / biosynthesis
  • Benz(a)Anthracenes / pharmacology
  • Benzopyrenes / pharmacology
  • Chrysenes / pharmacology
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Enzyme Induction
  • Epoxide Hydrolases / biosynthesis
  • Fluorenes / pharmacology
  • Isoenzymes / biosynthesis*
  • Male
  • Microsomes, Liver / enzymology*
  • NADPH-Ferrihemoprotein Reductase / biosynthesis
  • Nitro Compounds / pharmacology*
  • Oxygenases / biosynthesis
  • Polycyclic Compounds / pharmacology*
  • Pyrenes / pharmacology
  • Rats
  • Rats, Inbred Strains

Substances

  • Air Pollutants
  • Benz(a)Anthracenes
  • Benzopyrenes
  • Chrysenes
  • Fluorenes
  • Isoenzymes
  • Nitro Compounds
  • Polycyclic Compounds
  • Pyrenes
  • 7-nitrobenzanthracene
  • 3-nitrobenzo(a)pyrene
  • 1-nitrobenzo(a)pyrene
  • 6-nitrochrysene
  • Cytochrome P-450 Enzyme System
  • 1,3-dinitropyrene
  • Oxygenases
  • 7-Alkoxycoumarin O-Dealkylase
  • Aryl Hydrocarbon Hydroxylases
  • Aminopyrine N-Demethylase
  • NADPH-Ferrihemoprotein Reductase
  • Epoxide Hydrolases
  • 3-nitrofluoranthene
  • 1-nitropyrene