Carcinogenesis, Vol 19, 2055-2057, Copyright © 1998 by Oxford University Press
EM van Lieshout, MM Bedaf, M Pieter, C Ekkel, WA Nijhoff and WH Peters
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.
ARTICLES
Effects of dietary anticarcinogens on rat gastrointestinal glutathione S-transferase theta 1-1 levels
Department of Gastroenterology, St Radboud University Hospital, Nijmegen, The Netherlands.
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