A systematic gene expression screen of Caenorhabditis elegans cytochrome P450 genes reveals CYP35 as strongly xenobiotic inducible

Arch Biochem Biophys. 2001 Nov 15;395(2):158-68. doi: 10.1006/abbi.2001.2568.

Abstract

The soil nematode Caenorhabditis elegans is one of the simplest animals having the status of a laboratory model. Its genome contains 80 cytochrome P450 genes (CYP). In order to study CYP gene expression in C. elegans mixed stages and synchronized hermaphrodites were exposed to 18 known xenobiotic cytochrome P450 inducers. Messenger RNA expression was detected by DNA arrays and semiquantitative RT-PCR. Using subfamily-specific primers, a pooled set of exon-rich CYP fragments could be amplified. In this way it was possible to systematically check the influence of different inducers on CYP expression at the same time. The well-known CYP1A inducers beta-naphthoflavone, PCB52, and lansoprazol were the most active and in particular they strongly induced almost all CYP35 isoforms. A few number of further CYP forms were found to be inducible by other xenobiotics like phenobarbital, atrazine, and clofibrate. In addition, a transgenic C. elegans line expressing GFP under control of the CYP35A2 promoter showed a strong induction of the fusion by beta-naphthoflavone in the intestine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics*
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 Enzyme System / genetics*
  • DNA / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression / drug effects
  • Green Fluorescent Proteins
  • Intestinal Mucosa / metabolism
  • Lansoprazole
  • Luminescent Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Omeprazole / analogs & derivatives*
  • Omeprazole / pharmacology
  • Promoter Regions, Genetic
  • Protein Isoforms
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Xenobiotics / pharmacology
  • beta-Naphthoflavone / pharmacology

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Enzyme Inhibitors
  • Luminescent Proteins
  • Protein Isoforms
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Xenobiotics
  • Lansoprazole
  • Green Fluorescent Proteins
  • beta-Naphthoflavone
  • RNA
  • DNA
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP1A1
  • Omeprazole