Induction of glutathione-S-transferase mRNA levels by chemopreventive selenocysteine Se-conjugates

Peter a.C ’t Hoen, Martijn Rooseboom, Martin K Bijsterbosch, Theo J C van Berkel, Nico P E Vermeulen, Jan N M Commandeur

Research output: Contribution to JournalArticleAcademicpeer-review


Several selenocysteine Se-conjugates (SeCys-conjugates) prevent against chemically induced carcinogenesis. Bioactivation to selenols (RSeH) by beta-lyases is thought to be critical, but the mechanism of tumor suppression remains unclear. Induction of phase II biotransformation enzymes is a possible mechanism of chemoprevention. In this study, we evaluated the isoform-selective induction of glutathione-S-transferase (GST) at the mRNA level using a quantitative reverse transcriptase polymerase chain reaction assay. In cultured primary rat hepatocytes and H35 Reuber rat hepatoma cells, SeCys-conjugates time-dependently increased mRNA levels of GST Alpha isoforms and GST Pi, but not of GST Mu isoforms. Se-allyl-L-selenocysteine, the most potent chemopreventive SeCys-conjugate so far known, was also the most active GST inducer. After exposure for 24hr, it elevated GSTA2, GSTA3, GSTA5, and GSTP mRNA levels in primary hepatocytes 3.2+/-0.4-, 1.9+/-0.1-, 4.3+/-0.3-, and 2.9+/-0.3-fold, respectively. Se-allyl-D-selenocysteine was significantly less active, suggesting that stereoselective conversion of SeCys-conjugates to selenols is involved in GST induction. In H35 Reuber hepatoma cells, where conversion of SeCys-conjugates to selenols was 2-6-fold lower than in primary hepatocytes, GST induction was also much lower than in primary hepatocytes. SeCys-conjugates did not induce cytochrome P450 1A1, 2B1/2, or 3A1. This indicates that SeCys-conjugates are monofunctional inducers of phase II biotransformation enzymes. The present results suggest that induction of GST expression contributes to the chemopreventive activity of SeCys-conjugates.

Original languageEnglish
Pages (from-to)1843-9
Number of pages7
JournalBiochemical Pharmacology
Issue number10
Publication statusPublished - 15 May 2002


  • Animals
  • Cytochrome P-450 Enzyme System
  • Enzyme Induction
  • Glutathione Transferase
  • Hepatocytes
  • Lyases
  • RNA, Messenger
  • Rats
  • Selenium Compounds
  • Selenocysteine
  • Tumor Cells, Cultured
  • Journal Article


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