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Carcinogenesis Advance Access published online on August 1, 2003
Carcinogenesis, doi:10.1093/carcin/bgg122
© 2003 by Oxford University Press
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© 2003 Oxford University Press

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Expression of glutathione S-transferases (GST) in human colon cells and inducibility of GSTM2 by butyrate

Miriam Nannette Ebert 1, Annett Klinder 1, Wilbert H. M. Peters 2, Anja Schäferhenrich 1, Wolfgang Sendt 3, Johannes Scheele 3, and Beatrice Louise Pool-Zobel 1*

1 Department of Nutritional Toxicology, Institute for Nutrition, Friedrich-Schiller-University, Dornburger Straße 25, D-07743 Jena, Germany
2 Department of Gastroenterology, St Radboud University Hospital, Nijmegen, The Netherlands
3 Department of Surgery, Friedrich-Schiller-University, Bachstraße 18, D-07743 Jena, Germany

* Corresponding author. E-mail: b8bobe{at}uni-jena.de.

Received 19 November 2002 ; revised 26 May 2003 ; accepted 10 July 2003

Abstract

The glutathione S-transferases (GST's) are a multigene family of enzymes largely involved in the detoxification of chemicals. In animals enhanced expression is mediated by products of gut fermentation. Of these, butyrate induces GSTP1 protein expression and GST activity in the human colon tumor cell line HT29. Aim of the following investigations was to further elucidate butyrate-modulated induction of additional colonic GSTs in HT29 and to determine baseline expression in non-transformed cells, isolated from human colorectal tissue. We measured five GST protein subunits (GSTA1/2 - composed of GST A1-1, A1-2 and A2-2 - GSTM1, GSTM2, GSTP1, GSTT1) by Western blot, GST activity using 1-chloro-2,4-dinitrobenzene as substrate and GSTM2 mRNA expression with RT-PCR. GSTP1, followed by GSTT1, were major subunits in all colon cells. Cells isolated from colon tissue were identified to be colonocytes and colon fibroblasts, both which also expressed substantial levels of GSTM1 and GSTM2. The interindividual variation of GST-subunits in coloncytes of 15 individuals was marked, with total GST protein per 106 cells differing by more than a factor of four. In HT29, butyrate significantly enhanced GSTA1/2 (3.5 fold), GSTM2 (not detectable in controls), GSTP1 (1.5 fold) and GST activity (1.4 fold), but not GSTM1 or GSTT1. GSTM2 mRNA expression was significantly induced after 24 h (~14 fold) and 72 h treatment (~8 fold). In colon fibroblasts, butyrate (4 mM, 72 h) also induced GSTM2 protein (1.7 fold) and GST activity (1.4 fold). Colonocytes were too short lived to be used for inducibility studies. In conclusion, GSTs are expressed with high inter-individual variability in human colonocytes. This points large differences in cellular susceptibility to xenobiotics. However, butyrate, an important luminal component produced from fermentation of dietary fibers, is an efficient inducer of GSTs and especially of GSTM2. This indicates that butyrate may act chemoprotective by increasing detoxification capabilities in the colon mucosa.

butyrate, glutathione S-transferases, colon cells
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