Induction of rat liver microsomal and nuclear cytochrome P-450 by dietary 2-acetylaminofluorene and butylated hydroxytoluene

Biochem Pharmacol. 1989 Sep 15;38(18):3075-81. doi: 10.1016/0006-2952(89)90018-x.

Abstract

The influence of dietary 2-acetylaminofluorene (AAF) on the cytochrome P-450 content of rat liver microsomal and nuclear fractions was immunochemically probed with monoclonal and polyclonal antibodies to cytochromes P-450c and P-450d. Cytochrome P-450d but not P-450c was immunodetected in microsomes, nuclear envelopes, and nuclei from untreated rats. The levels of both cytochromes P-450c and P-450d were elevated after a diet of either 0.1% AAF for 1 week or 0.05% AAF for 3 weeks. However, the level of cytochrome P-450c relative to P-450d was lower after the more prolonged AAF feeding. Supplementation of AAF-containing diets with 0.3% butylated hydroxytoluene (BHT), which affords protection against AAF hepatocarcinogenesis in high-fat fed rats, protected and/or induced total (spectral) nuclear envelope cytochrome P-450 content. Immunochemical studies of liver fractions showed that BHT enhanced the AAF-dependent induction of cytochrome P-450c, but not of P-450d. This was a concerted effect of AAF + BHT since dietary BHT by itself did not affect the levels of cytochrome P-450c or P-450d as compared to control rats. Since 1- to 3-week dietary AAF had little effect on total (spectral analyses) microsomal cytochrome P-450 but markedly reduced total P-450 in nuclear envelopes, the coordinated induction of specific cytochrome P-450s in the different fractions suggests selective induction and depression of different forms of cytochrome P-450 and provides additional evidence for independent regulation of the drug-metabolizing system in nuclear envelope and microsomes. In addition, these results suggest that regulation of cytochrome P-450 may play a crucial role in the nutritional modulation of AAF hepatocarcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Acetylaminofluorene / pharmacology*
  • Animals
  • Antibodies, Monoclonal
  • Butylated Hydroxytoluene / pharmacology*
  • Cell Nucleus / enzymology*
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / immunology
  • Diet
  • Enzyme Induction / drug effects
  • Immunoblotting
  • Male
  • Methylcholanthrene / pharmacology
  • Microsomes, Liver / enzymology*
  • Rats
  • Rats, Inbred Strains

Substances

  • Antibodies, Monoclonal
  • Butylated Hydroxytoluene
  • Methylcholanthrene
  • Cytochrome P-450 Enzyme System
  • 2-Acetylaminofluorene