Low glutathione and glutathione S-transferase levels in Barrett's esophagus as compared to normal esophageal epithelium

Patients with Barrett's esophagus, wherein squamous epithelium has been rep laced by columnar epithelium, have an increased risk for developing esophag eal adenocarcinoma as compared to the general population, Glutathione S-tra nsferase (GST), a family of detoxification enzymes consisting of class alph a, mu, pi, and theta isoforms, is invoiced in detoxification of carcinogens and low levels of these enzymes correlated with high cancer risk. We have now compared GST enzyme activity, GST isoenzyme composition and glutathione (GSH) content of Barrett's mucosa with that of adjacent normal squamous ep ithelium. Biopsy specimens of 98 patients with Barrett's esophagus were tak en from both Barrett's and adjacent normal squamous epithelium, GST enzyme activity towards 1-chloro-2,4-dinitrobenzene was measured, and GST isoenzym e levels were determined by densitometrical analyses of western blots after immunodetection with monoclonal antibodies, Total GSH content was determin ed by high-performance liquid chromatography after conjugation with monobro mobimane. Wilcoxon's signed rank test and Spearman correlation analyses wer e used for statistical evaluation, As compared with adjacent normal squamou s epithelium, GST enzyme activity in Barrett's epithelium was reduced by 35 %, and GST mu, GST pi and GSH levels were reduced by 23%, 30%, and 63%, res pectively, However, the minor GST alpha and GST theta levels were higher in Barrett's epithelium (by 625% and 33%, respectively). High levels of GSH a nd GSTs in general are correlated with protection against cellular or cytog enetic damage. The observed reduction in GSTs and GSH in Barrett's epitheli um may therefore contribute to the increased cancer risk in this tissue.