Role of glutathione in cellular resistance to alkylating agents.
Both elevated glutathione levels and increased activity of the enzyme glutathione S-transferase have been associated with the resistance of cells to alkylating agents. We have demonstrated that one mechanism of this resistance is the inactivation of the alkylating agents by conjugation with glutathione. This conjugation can be catalyzed by glutathione S-transferase. For the nitrogen mustard agents we have studied, both the spontaneous and enzyme catalyzed reactions proceed through the aziridinium intermediates of the alkylating agents, and the alpha isoenzymes of GST are involved. In a study of cyclophosphamide resistant medulloblastoma cell lines elevated cellular concentrations of glutathione correlated well with the resistance of the cell lines.
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- Tumor Cells, Cultured
- Rabbits
- Phosphoramide Mustards
- Mice
- Melphalan
- In Vitro Techniques
- Humans
- Glutathione Transferase
- Glutathione
- Drug Resistance
Citation
Published In
DOI
ISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- Tumor Cells, Cultured
- Rabbits
- Phosphoramide Mustards
- Mice
- Melphalan
- In Vitro Techniques
- Humans
- Glutathione Transferase
- Glutathione
- Drug Resistance