Glutathione S-transferase and glutathione peroxidase expression in normal and tumour human tissues.
Glutathione S-transferases play a central role in drug detoxification and have been implicated in the sensitivity of tumour cells to anticancer drugs. In this study, glutathione S-transferase (GST) isozyme expression in normal and tumour tissue from human lung, colon, stomach, breast, kidney and liver tissue has been quantified using sensitive and subunit specific radioimmunoassays (RIA), together with Western blot analysis and measurement of substrate metabolism. Glutathione S-transferase pi was the predominant GST in the majority of the tumours examined. The concentration of this enzyme was increased significantly in tumour tissue relative to normal lung, colon, and stomach tissue. A strong correlation was observed (r = 0.77, P less than 0.01) between GST activity and GST pi levels in those tumour samples. The concentrations of the alpha class GST, the predominant isoenzymes in normal stomach, kidney and liver, decreased dramatically in tumour tissue from these organs. Western blot analysis revealed the presence of novel polypeptides that cross-reacted with antisera raised against alpha and mu class GST. Our data demonstrates that although GST pi is the predominant GST isoenzyme in many tumours, significant levels of the other GST subunits are also present and collectively can represent a significant proportion of the GST content. Therefore the properties of all the GST isoenzymes need consideration when assessing the role of these proteins in drug resistance. Selenium-dependent glutathione peroxidase, an enzyme activity also implicated in the mode of action of certain antitumour agents, was also studied and shown to be the predominant glutathione-dependent peroxidase in all tumours except the hepatoma.
Howie
A F
AF
Department of Clinical Chemistry, University of Edinburgh, Royal Infirmary, UK.
Forrester
L M
LM
Glancey
M J
MJ
Schlager
J J
JJ
Powis
G
G
Beckett
G J
GJ
Hayes
J D
JD
Wolf
C R
CR
D015153:Blotting, Western; D005979:Glutathione Peroxidase / Q000032:analysis*; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D009369:Neoplasms / Q000201:enzymology*; D011863:Radioimmunoassay
D007527:Isoenzymes; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase