Cellular glutathione as a protective agent against 4-hydroperoxycyclophosphamide cytotoxicity in K-562 cells

  title={Cellular glutathione as a protective agent against 4-hydroperoxycyclophosphamide cytotoxicity in K-562 cells},
  author={Richard H. Peters and K. Ballard and John E. Oatis and David J. Jollow and Robert K. Stuart},
  journal={Cancer Chemotherapy and Pharmacology},
SummaryExposure of cells of the K-562 erythroleukemia cell line to 4-hydroperoxycyclophosphamide (4-HC), an analog of activated cyclophosphamide, causes a concentration-dependent inhibition of in vitro colony formation by these cells. For investigation of the role of glutathione (GSH) in the metabolism of 4-HC, GSH levels of K-562 cells were modulated by exposing the cells to buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, and/or to GSH ethyl esters. Both the mono- and… 
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Glutathione depletion as a determinant of sensitivity of human leukemia cells to cyclophosphamide.
The role of glutathione (GSH) as a determinant of cellular sensitivity to the cytotoxic and DNA-damaging effects of cyclophosphamide (CP) was studied in a dual culture system of rat hepatocytes and
Effect of glutathione depletion by L-buthionine sulfoximine on the cytotoxicity of cyclophosphamide in single and fractionated doses to EMT6/SF mouse tumors and bone marrow.
A possible role for BSO as a clinical chemosensitizer, which could be combined with fractionated doses of CYC and may be effective on small cancerous lesions is suggested.
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Acrolein in vivo preferentially reacts with glutathione, and sulfhydryl-containing compounds may protect against acrolein toxicity and at the same time not interfere with the chemotherapeutic activity of CP.
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Administration of N-acetylcysteine or sodium-2-mercaptoethane sulfonate with cyclophosphamide, while not protecting against leukopenia, protected against the enzymatic inactivation and urotoxicity.
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A preliminary evaluation of the curative effect after a single IV injection of 4-(S-ethane)-and 4-ethanol)-sulfidocyclophosphamide in rats bearing Yoshida ascites sarcoma or in nu/nu mice bearing human breast carcinoma xenografts suggested that these sulfido derivatives possess the same oncostatic efficacy as activated cycloph phosphamide itself.
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At concentrations resulting in equivalent toxicity to marrow CFU-GM, cisplatin seemed to be more toxic to murine spleen blast colony forming cells (CFC-BC) than 4-HC, and the drugs in combination appeared to have at least additive toxicities against CFC- BC.
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    Cancer treatment reports
  • 1976
3-Hydroxypropylmercapturic acid (MCA) has been quantitatively determined in the urine of rats given cyclophosphamide (CP), related antineoplastic agents, allyl alcohol, or acrolein, with a simple