Quantification of induction of rat oesophageal, gastric and pancreatic glutathione and glutathione S-transferases by dietary anticarcinogens.

Abstract

Four dietary, naturally occurring anticarcinogens (flavone, coumarin, alpha-angelicalactone and ellagic acid) were studied with respect to their effects on oesophageal, gastric and pancreatic (i) glutathione S-transferase (GST) enzyme activity, (ii) GST isozyme levels and (iii) glutathione (GSH) content in male Wistar rats. GST enzyme activity was significantly increased in the oesophagus by flavone, coumarin and alpha-angelicalactone (125, 240 and 155% respectively) and in the stomach by coumarin and alpha-angelicalactone (140 and 230%). No change in pancreatic GST activity was observed. In addition, class- and tissue-specific changes in GST isozyme levels occurred. Class alpha GSTs were induced in the oesophagus by flavone, coumarin and alpha-angelicalactone (570, 1580 and 570%), but did not change in the stomach. GST-alpha was undetectable in the pancreas. GST-mu was expressed at high levels in all three tissues investigated, but only pancreatic GST-mu levels of ellagic acid-fed rats were increased (160%). GST-pi was induced in the stomach by coumarin and alpha-angelicalactone (470 and 1120%) and in the pancreas by flavone (200%). GST-pi was detectable at low levels in rat oesophageal epithelium of coumarin-fed animals only. GSH concentrations were uninfluenced by the dietary anticarcinogens in all tissues. These results suggest that dietary ellagic acid and, more especially, flavone, coumarin and alpha-angelicalactone may exert strong chemoprotective effects by selective enhancement of members of the GST detoxification system in the oesophagus or stomach and, to a lesser extent, in the pancreas.