Detoxifying enzymes in human ovarian tissues: comparison of normal and tumor tissues and effects of chemotherapy.
Many anticancer drugs exert their cytotoxic effects via formation of oxygen free radicals. Cellular thiols, glutathione (GSH)-dependent enzymes and other redox enzymes are involved in the metabolism of these anticancer drugs and of the oxygen free radicals that may be generated during their metabolism. We quantified these biochemical parameters in cytosol from human ovarian tissues. We compared non-protein thiol levels, GSH transferase, GSH peroxidase, superoxide dismutase, catalase, DT diaphorase and aldehyde dehydrogenase activity in serous ovarian tumors (n = 15), other malignant ovarian tumors (n = 12), benign ovarian tissue (n = 10) and histologically normal ovarian tissue (n = 12). Mean GSH transferase and DT diaphorase activities were similar in serous and other malignant ovarian tumors. GSH transferase activity was decreased in malignant tissues relative to normal and benign tissues. Mean DT diaphorase and superoxide dismutase activities were increased in the malignant tissues, although this was not statistically significant. The mean levels of all enzymes except superoxide dismutase and aldehyde dehydrogenase in benign tissues were fairly similar to the mean levels found in normal tissue samples. Tissues from patients with serous ovarian tumors, who had received cyclophosphamide and cisplatin prior to surgery, also were analyzed (n = 7). Except for aldehyde dehydrogenase, all the parameters measured were decreased in these samples relative to serous tissue from untreated patients. These biochemical analyses may be useful in understanding the mechanisms involved in the response to chemotherapy.
Djuric
Z
Z
Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201.
Malviya
V K
VK
Deppe
G
G
Malone
J M
JM
McGunagle
D L
DL
Heilbrun
L K
LK
Reading
B A
BA
Lawrence
W D
WD
D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000032:analysis; D000970:Antineoplastic Agents / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis* / Q000037:antagonists & inhibitors; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D010053:Ovary / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000032:analysis
D000970:Antineoplastic Agents; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000444:Aldehyde Dehydrogenase; D005982:Glutathione Transferase