Several dietary compounds have been demonstrated to reduce gastrointestinal cancer rates in both humans and animals. We showed that high human gastrointestinal tissue levels of glutathione S-transferase (GST), a family of detoxification enzymes consisting of class Alpha, Mu, Pi and Theta isoforms, were inversely correlated with cancer risk. We now investigated whether the sulforaphane analog compound 30, indole-3-carbinol, d-limonene or relafen, supplemented in the diet for two weeks at 1450, 250, 10 000, and 200 ppm, respectively, influenced (i) GST activity, (ii) GST isoenzyme levels, (iii) GSH levels, or (iv) glutathione peroxidase (GPx) activity in the gastrointestinal tract of male Wistar rats. Sulforaphane analog compound 30 enhanced GST activity in all organs studied (1.2–2.4×). It induced GST Alpha levels in small intestine and liver, GST Mu levels in stomach and small intestine, GST Pi levels in stomach and small and large intestine, and GSH levels in stomach and proximal and middle small intestine. Indole-3-carbinol induced gastric GST Mu and hepatic GST Alpha levels. d-limonene induced hepatic GST Alpha, colonic GST Pi levels and proximal small intestinal GST enzyme activity and GST Pi levels. Relafen induced hepatic GST Alpha levels, distal small intestinal and gastric GST Pi levels, and oesophageal and proximal small intestinal GSH levels. GPx activity was enhanced by relafen in oesophagus, and in distal small intestine by sulforaphane analog compound 30. Enhancement of GSTs and to a lesser extent GPx and GSH, resulting in a more efficient detoxification, may explain at least in part the anticarcinogenic properties of sulforaphane analog compound 30, and to a much lesser extent of indole-3-carbinol and d-limonene.
This work was supported by grant KUN 94–715 (EMMvL) from the Dutch Cancer Society and at Johns Hopkins by the NIH (BTW and GHP).