Effects of dietary anticarcinogens on rat gastrointestinal glutathione S-transferase theta 1-1 levels.
Several naturally occurring food components or non-steroidal 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 mechanisms that lead to cancer prevention. We therefore investigated whether the anticarcinogens alpha-angelicalactone, alpha-tocopherol, beta-carotene, coumarin, ellagic acid, flavone, indole-3-carbinol, d-limonene, oltipraz, phenethylisothiocyanate (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 alpha-angelicalactone, alpha-tocopherol, coumarin, ellagic acid, oltipraz, PEITC and the sulphoraphane analogue compound-30. Oesophageal rGSTT1-1 protein levels were elevated by a-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.
van Lieshout
E M
EM
Department of Gastroenterology, St Radboud University Hospital, Nijmegen, The Netherlands.
Bedaf
M M
MM
Pieter
M
M
Ekkel
C
C
Nijhoff
W A
WA
Peters
W H
WH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D004064:Digestive System / Q000201:enzymology*; D005638:Fruit; D005770:Gastrointestinal Neoplasms / Q000517:prevention & control; D005982:Glutathione Transferase / Q000032:analysis*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014675:Vegetables
D016588:Anticarcinogenic Agents; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase