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Glutathione-linked detoxification pathway in normal and malignant human bladder tissue
S V Singh1, B H Xu, G T Tkalcevic
1Cancer Research Laboratory, Mercy Cancer Center, Mercy Hospital of Pittsburgh, PA 15219.
Cancer Letters
|February 28, 1994
Summary
This study investigated glutathione (GSH) and related enzymes in bladder cancer, finding elevated GSH peroxidase and catalase in tumors. These enzymes may contribute to drug resistance and serve as potential cancer markers.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Glutathione (GSH) and its dependent enzymes are crucial in cellular defense and have been linked to anti-cancer drug resistance.
- Bladder cancer exhibits a high incidence of inherent drug resistance, necessitating research into its underlying mechanisms.
Purpose of the Study:
- To compare the levels of GSH and GSH-dependent detoxification enzymes in paired normal and malignant human bladder tissues.
- To investigate the potential role of these enzymes in the intrinsic drug resistance of bladder tumors.
- To explore the possibility of using GSH-dependent enzymes as biomarkers for bladder neoplasia.
Main Methods:
- Comparative analysis of glutathione (GSH) content, GSH reductase, GSH peroxidase, catalase activity, and glutathione transferase (GST) isoenzyme expression.
- Examination of paired normal and malignant human bladder tissues from patients.
Main Results:
- Mean GSH content and GSH reductase activity showed no significant difference between normal and tumor tissues.
- Bladder tumors exhibited significantly higher mean GSH peroxidase activity (1.5-fold) and catalase activity (1.4-fold) compared to normal tissues.
- While GST activity did not differ significantly overall, GST pi was overexpressed in 60% of tumors, whereas GST alpha and mu were less frequent in tumors than normal tissues.
Conclusions:
- Elevated GSH peroxidase, catalase, and GST pi in bladder tumors may contribute to intrinsic drug resistance.
- GSH peroxidase and/or catalase could potentially serve as biomarkers for bladder neoplasia, warranting further validation with larger sample sizes.