Glutathione S-transferase activity and isoenzyme composition in benign ovarian tumours, untreated malignant ovarian tumours, and malignant ovarian tumours after platinum/cyclophosphamide chemotherapy.
Glutathione S-transferase (GST) isoenzyme composition, isoenzyme quantities and enzymatic activity were investigated in benign (n = 4) ovarian tumours and malignant ovarian tumours, before (n = 20) and after (n = 16) chemotherapy. Enzymatic activity of GST in cytosols was measured by determining 1-chloro-2,4-dinitrobenzene conjugation with glutathione, cytosolic GST subunits were determined by wide pore reversed phase HPLC, using a S-hexylglutathione-agarose affinity column, and isoelectric focussing. Both GST activity and GST pi amount were not related to histopathologic type, differentiation grade, or tumour volume index in untreated malignant tumours. GST isoenzyme patterns were identical in benign tumours and malignant tumours before and after platinum/cyclophosphamide chemotherapy, while GST pi was the predominant transferase. Mean GST activity and GST pi amount were decreased (P < 0.05) in malignant ovarian tumours after platinum/cyclophosphamide chemotherapy compared to untreated ovarian malignant tumours. No relation was found in untreated ovarian tumours between GST pi amount and response to platinum/cyclophosphamide chemotherapy. Thus, within the limitations of the current study no arguments were found for a role of GST in in vivo drug resistance of malignant ovarian tumours to platinum/cyclophosphamide chemotherapy.
van der Zee
A G
AG
Department of Gynaecology, University Hospital, Groningen, Netherlands.
van Ommen
B
B
Meijer
C
C
Hollema
H
H
van Bladeren
P J
PJ
de Vries
E G
EG
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003537:Cystadenoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D003600:Cytosol / Q000201:enzymology; D004351:Drug Resistance; D005260:Female; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D046911:Macromolecular Substances; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D007527:Isoenzymes; D046911:Macromolecular Substances; D003520:Cyclophosphamide; D005982:Glutathione Transferase; D002945:Cisplatin