| Abstrakt: |
Several naturally occurring food components or nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce gastrointestinal cancer rates. Recently we have shown that dietary administration of such compounds enhanced the glutathione S-transferase (GST) enzyme activity and class alpha, mu and pi isoenzyme levels in the rat gastrointestinal tract. Elevation of the levels of GSTs, a family of biotransformation enzymes with many functions such as detoxification of carcinogens, might be one of the mechanism that lead to cancer prevention. We therefore investigated whether the anticarcinogens α-angelicalactone, α-tocopherol, β-carotene, coumarin, ellagic acid, flavone, indole-3-carbinol, d-limonene, oltipraz, phenethylisotheiocyanate (PEITC) and the sulphoraphane analogue compound-30 affect gastrointestinal rGSTT1-1 protein levels in male Wistar rats. rGSTT1-1 protein levels were determined in cytosolic fractions of liver and oesophageal-, gastric-, small intestinal- and colonic mucosa by densitometrical analyses of western blots after immunodetection with an anti-human GSTT1-1 monoclonal antibody, that cross-reacts with rGSTT1-1. In control Wistar rats, gastrointestinal rGSTT1-1 protein levels were highest in the liver and decreased in the order liver > stomach > colon > oesophagus > small intestine. Gastric rGSTT1-1 protein levels were enhanced by α-angelicalactone, α-tocopherol, coumarin, ellagic acid, oltipraz, PEITC and the sulphoraphane analogue compound-30. Oesophageal rGSTT1-1 protein levels were elevated by α-angelicalactone and coumarin, whereas colonic rGSTT1-1 protein levels were elevated by coumarin. Ellagic acid, on the other hand, reduced hepatic rGSTT1-1 protein levels to 53% of the control. In conclusion, dietary anticarcinogens are capable of inducing rGSTT1-1 protein levels in the rat gastrointestinal tract, and are most pronounced in the stomach. Enhanced rGSTT1-1 protein levels might lead to an increase of enzyme activity and to a more efficient detoxification of carcinogens and thus could contribute to prevention of carcinogenesis. |
