EFFECTS OF DIETARY ANTICARCINOGENS ON RAT GASTROINTESTINAL GLUTATHIONE-S-TRANSFERASE THETA 1-1 LEVELS

Several naturally occurring food components or nonsteroidal anti-infla mmatory drugs (NSAIDs) may reduce gastrointestinal cancer rates. Recen tly we have shown that dietary administration of such compounds enhanc ed the glutathione S-transferase (GST) enzyme activity and class alpha , mu and pi isoenzyme levels in the rat gastrointestinal tract, Elevat ion of the levels of GSTs, a family of biotransformation enzymes with many functions such as detoxification of carcinogens, might be one of the mechanisms that lead to cancer prevention. We therefore investigat ed whether the anticarcinogens alpha-angelicalactone, alpha-tocopherol , beta-carotene, coumarin, ellagic acid, flavone, indole-3-carbinol, d -limonene, oltipraz, phenethylisothiocyanate (PEITC) and the sulphorap hane analogue compound-30 affect gastrointestinal rGSTT1-1 protein lev els in male Wistar rats. rGSTT1-1 protein levels were determined in cy tosolic fractions of liver and oesophageal-, gastric-, small intestina l- and colonic mucosa by densitometrical analyses of western blots aft er immunodetection with an anti human GSTT1-1 monoclonal antibody, tha t cross-reacts with rGSTT1-1. In control Wistar rats, gastrointestinal rGSTT1-1 protein levels were highest in the liver and decreased in th e order liver > stomach > colon > oesophagus > small intestine, Gastri c rGSTT1-1 protein levels were enhanced by alpha-angelicalactone, alph a-tocopherol, coumarin, ellagic acid, oltipraz, PEITC and the sulphora phane analogue compound-30. Oesophageal rGSTT1-1 protein levels were e levated by alpha-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 prono unced in the stomach. Enhanced rGSTT1-1 protein levels might lead to a n increase of enzyme activity and to a more efficient detoxification o f carcinogens and thus could contribute to prevention of carcinogenesi s.