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.

Effects of dietary anticarcinogens on rat gastrointestinal glutathione peroxidase activity.

Several naturally occurring and synthetic food components reduce gastrointestinal cancer. Many of these compounds are scavengers of free radicals, formed during oxidative stress. Glutathione peroxidases (GPxs) protect against free radicals by catalysing their inactivation, thereby consuming glutathione (GSH). This might be one of the mechanisms leading to cancer prevention. We studied the effect of several dietary anticarcinogens on gastrointestinal GPx enzyme activities in male Wistar rats. Total as well as selenium-dependent and non-selenium-dependent GPx (t-GPx, Se-GPx and nSe-GPx) enzyme activities were determined in cytosolic fractions of oesophagus, gastric and colonic mucosa and liver. d-Limonene induced all three types of GPx activities in the oesophagus. d-Limonene and PEITC induced colonic t-GPX and nSe-GPx activity. beta-Carotene induced all three colonic GPx activities and hepatic t-GPx and Se-GPx activity. Coumarin and alpha-tocopherol induced gastric t-GPx and colonic nSe-GPx activity. Oltipraz enhanced oesophageal and gastric t-GPx and oesophageal, gastric and colonic Se-GPx. All other anticarcinogens induced one type of GPx activity at one site. In conclusion, the specific enhancement of GPx enzyme activities by dietary anticarcinogens might lead to a more efficient reduction of organic hydroperoxides and hydrogen peroxide and thus add to prevention of carcinogenesis in these organs.