Carcinogenesis Advance Access published online on March 3, 2005
Carcinogenesis, doi:10.1093/carcin/bgi059
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1 Department of Nutritional Toxicology, Institute for Nutrition, Friedrich-Schiller-University, Dornburger Str. 25, D-07743 Jena, Germany
* To whom correspondence should be addressed. Butyrate, formed by bacterial fermentation of plant foods, has been suggested to reduce colon cancer risks by suppressing proliferation of tumor cells. Butyrate additionally has been shown to induce glutathione S-transferases (GSTs) in tumor cell lines, which may contribute to the detoxification of dietary carcinogens. We hypothesise that butyrate also affects biotransformation in non-transformed colon cells. Thus, we have investigated gene expression of drug metabolism genes in primary human colon tissue, premalignant LT97 adenoma and HT29 tumor cells cultured in appropriate medium ± butyrate. 96 drug metabolism genes (including 12 GSTs) spotted on cDNA macroarrays (Superarray®; n=3) were hybridized with Biotin-labelled cDNA probes. To validate expression detected with Superarray®, samples of LT97 cells were also analyzed with high density microarrays (Affymetrix® U133A), which include biotransformation genes that overlap with the set of genes represented on the Superarray®. Relative expression levels were compared across colon samples and for each colon sample ± butyrate. Compared to fresh tissue, 28 genes were down regulated in primary cells cultivated ex vivo, whereas 8 genes were up regulated. Several genes were less expressed in LT97 (27 genes) or in HT29 (34 and 33 genes, grown for 72 and 48 hours, respectively) compared to primary colon cells. Butyrate induced GSTP1, GSTM2, and GSTA4 in HT29 as previously confirmed by other methods (Northern Blot/qPCR). We detected an up regulation of GSTs (GSTA2, GSTA3, GSTA4, GSTT2) that are known to be involved in defence against oxidative stress in primary cells upon incubation with butyrate. The changes in expression detected in LT97 by Superarray® and Affymetrix® were similar confirming the validity of the results. We conclude that low GST expression levels were favourably altered by butyrate. An induction of the toxicological defence system possibly contributes to reported chemopreventive properties of butyrate, a product of dietary fibre fermentation in the gut. *The studies were done with c-DNA macroarrays, containing sequences of 96 genes related to drug metabolism, the data for the 12 spotted genes belonging to the family of the glutathione S-transferases are presented here in more detail, since confirmatory studies are available. Data for the other genes of drug metabolism are available from the accessory data file (http://www2.uni-jena.de/biologie/ieu/et/Dateien/Butyrate_gene.pdf).
Received August 13, 2004
Revised February 10, 2005
Accepted February 20, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Butyrate may enhance toxicological defence in primary, adenoma and tumor human colon cells by favourably modulating expression of glutathione S-transferases genes, an approach in nutrigenomics*
2 Department of General and Visceral Surgery, Clinic for Surgery, Friedrich-Schiller-University, Erlanger Allee 101, D-07745 Jena, Germany
3 Department of Molecular Medicine, Clinic for Internal Medicine II, Friedrich-Schiller-University, Erlanger Allee 101, D-07743 Jena, Germany
Beatrice Louise Pool-Zobel, E-mail: b8pobe{at}uni-jena.de
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