Inducibility of various cytochrome P450 isozymes by phenobarbital and some other xenobiotics in Drosophila melanogaster

Biochem Pharmacol. 1994 May 18;47(10):1867-73. doi: 10.1016/0006-2952(94)90317-4.

Abstract

The inducibility of cytochrome P450 isozymes has been investigated in the Drosophila melanogaster insecticide susceptible (Oregon R) and insecticide resistant (91R) strains. Both the level and induction kinetics of 7-ethoxycoumarin O-deethylase activity were stimulated by phenobarbital (PB) to a lower extent than that of aryl hydrocarbon hydroxylase in the Oregon R strain. The basal level of the cytochrome P450-linked activities in insecticide resistant flies was higher than that noted in susceptible ones. However, treatment with PB has increased levels of 7-ethoxycoumarin O-deethylase and aryl hydrocarbon hydroxylase activities more in susceptible flies than in resistant ones. In contrast to PB, the polycyclic aromatic hydrocarbon benzo[a]pyrene induced both activities in 91R flies to a greater extent than in Oregon R ones. The potent PB-like inducer in mice but not in rats 1.4-bis[2-(dichloropyridyloxy)]-benzene failed to induce the cytochrome P450 system in D. melanogaster, when triphenyldioxane (PB-like inducer in rats but not in mice) markedly affected this system in a PB-like manner. The SDS-PAGE followed by immunoblotting analysis using monoclonal antibodies 13-2e and 8-1d have shown that the level of the 56,000 and 54,000 Da insecticide resistance-related forms has increased in the susceptible strain by PB and some other PB like inducers. The relationship between these isozymes appearance and 7-ethoxycoumarin O-deethylase activity has been discussed.

Publication types

  • Comparative Study

MeSH terms

  • 7-Alkoxycoumarin O-Dealkylase / biosynthesis
  • Animals
  • Aryl Hydrocarbon Hydroxylases / biosynthesis
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Drosophila melanogaster / drug effects*
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics
  • Enzyme Induction
  • Isoenzymes / biosynthesis*
  • Phenobarbital / pharmacology*

Substances

  • Isoenzymes
  • Cytochrome P-450 Enzyme System
  • 7-Alkoxycoumarin O-Dealkylase
  • Aryl Hydrocarbon Hydroxylases
  • Phenobarbital