ENHANCEMENT OF RAT HEPATIC AND GASTROINTESTINAL GLUTATHIONE AND GLUTATHIONE S-TRANSFERASES BY ALPHA-ANGELICALACTONE AND FLAVONE

The naturally occurring anticarcinogens flavone and alpha-angelicalact one incorporated separately and simultaneously in the diet at 0.5, 0.1 , 0.05 and 0.01% w/w, were studied with respect to their effects on oe sophageal, gastric, intestinal, colonic and hepatic (i) glutathione S- transferase (GST) enzyme activity, (ii) GST isozyme levels and (iii) g lutathione (GSH) content in male Wistar rats. GST enzyme activity was significantly increased in the three treatment groups at one or more s ites. The most substantial inductions were seen in oesophagus and stom ach by 0.5% alpha-angelicalactone (1.9- and 2.3-fold respectively); an d in small intestine, colon and liver by 0.5% combination diet (2.5-, 1.4- and 4.0-fold respectively). The inducing capacities declined with decreasing anticarcinogen concentrations, GST enzyme activity was ind uced in liver and to a lesser extent in small intestine and stomach. I n general, in combination groups similar effects were seen as after tr eatment with alpha-angelicalactone or flavone separately, However, col onic GST enzyme activity was increased in the 0.5% combination group ( 1.4-fold), whereas in the corresponding flavone or alpha-angelicalacto ne groups no induction was observed. Concomitant changes in GST isozym e levels occurred. The involvement was the highest for GST-alpha (75%) , followed by GST-mu (58%) and GST-pi (33%). Increased GSH levels were obtained in stomach and liver in all three treatment groups at variou s concentrations. These data demonstrate that dietary administration o f flavone or alpha-angelicalactone, even at relatively low concentrati ons, may exert chemopreventive effects in stomach, small intestine, li ver and to a lesser extent in oesophagus by enhancing the GST detoxifi cation system, mainly by induction of GST-alpha and GST-mu isozymes. I n addition, simultaneous administration of flavone and alpha-angelical actone may result in anticarcinogenic effects in the colon by the same principle.