| ABSTRACT: |
|
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. |