Regioselective inhibition of benzo(a)pyrene metabolism by corticosterone in comparison with metyrapone and alpha-naphthoflavone

Toxicol Lett. 1986 Apr;31(1):57-64. doi: 10.1016/0378-4274(86)90194-3.

Abstract

Corticosterone was investigated for its ability to inhibit benzo(a)pyrene (BaP) metabolism and was compared to metyrapone and alpha-naphthoflavone. Corticosterone inhibited aryl hydrocarbon hydroxylase (AHH) activity nonlinearly in hepatic microsomes from uninduced, phenobarbital-induced, or 3-methylcholanthrene-induced rats. When compared to the classic inhibitors metyrapone and alpha-naphthoflavone, corticosterone had inhibitory properties similar to each. Metabolism of BaP to dihydrodiols was inhibited at the K-region by corticosterone only in uninduced microsomes. Dihydrodiol formation at the Bay region, which leads to the putative ultimate carcinogen, was not affected by corticosterone in uninduced or phenobarbital-induced microsomes but stimulated in 3-methylcholanthrene-induced microsomes. These findings suggest that corticosterone regioselectively inhibits cytochrome P-450 mediated oxidation of BaP to less mutagenic metabolites while stimulating the formation of highly mutagenic products.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Benzo(a)pyrene / antagonists & inhibitors*
  • Benzo(a)pyrene / metabolism
  • Benzoflavones / toxicity*
  • Chromatography, High Pressure Liquid
  • Corticosterone / toxicity*
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Flavonoids / toxicity*
  • Injections, Intraperitoneal
  • Male
  • Methylcholanthrene / pharmacology
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism
  • Pentobarbital / pharmacology
  • Pyridines / toxicity*
  • Rats
  • Rats, Inbred Strains

Substances

  • Benzoflavones
  • Flavonoids
  • Pyridines
  • metapyrone
  • Benzo(a)pyrene
  • Methylcholanthrene
  • alpha-naphthoflavone
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • Pentobarbital
  • Corticosterone