Glutathione-linked detoxification pathway in normal and malignant human bladder tissue.

Abstract

This study compares the levels of glutathione (GSH) and GSH-dependent detoxification enzymes, which have been implicated in anti-cancer drug resistance, in paired normal and malignant human bladder tissues, a tumor with high incidence of inherent drug resistance. Although the mean GSH transferase (GST) activity did not differ significantly in normal and neoplastic bladder tissues, this enzyme activity was relatively higher in tumor tissues of five out of ten patients as compared with corresponding normal tissues. Similarly, the mean GSH content and GSH reductase activity did not differ significantly between normal and neoplastic bladder tissues. On the other hand, the mean GSH peroxidase activity towards cumene hydroperoxide and catalase activity in bladder tumors was higher by about 1.5 and 1.4 times, respectively (P < 0.05), compared with those of normal tissues. GST isoenzymes corresponding to the three major classes (alpha, mu and pi) were expressed in every normal bladder tissue examined in the present study. Overexpression of GST pi was observed in 60% of the bladder tumors, whereas alpha and mu type GST proteins in tumor tissues were lower at frequencies of 62.5% and 37.5%, respectively, compared with the corresponding normal tissues. These results suggest that (a) elevated levels of GSH peroxidase, catalase and GST pi in human bladder tumors may contribute, at least in part, to the intrinsic drug resistance of this neoplasm and (b) anti-oxidative enzymes GSH peroxidase and/or catalase may represent markers for this neoplasia, although a large number of tissue specimens must be analyzed to validate this hypothesis.