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Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells

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Summary

Biopsy samples and cultured cells derived from them were obtained from 39 patients with malignant glioma and were analyzed for 1) glutathione (GSH) content; 2) sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or nitrogen mustard (HN2) treatment and 3) the effect of buthionine sulfoximine (BSO) treatment on BCNU and/or HN2 cytotoxicity. The average GSH concentration of biopsy specimens was lower than those of cultured cells (2.36±0.44 vs. 11.42±2.32 nmol/106 cells). While some of the tumor specimens were sensitive to either BCNU or HN2, the majority were resistant to both. However, 8 of 23 tumors tested showed enhanced sensitivity to BCNU following treatment with BSO. Five of 17 tumors were similarly sensitized to HN2 by BSO. These results suggest that BSO chemosensitization may be of value for certain patients and that screening assays may help identify treatment-sensitive individuals.

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Authors and Affiliations

  1. Radiobiology Laboratory, Department of Radiation Oncology, Cross Cancer Institute, T6G 1Z2, Edmonton, Alberta

    M. Joan Allalunis-Turner

  2. Molecular Genetics and Carcinogenesis Laboratory, Department of Medicine, Cross Cancer Institute, T6G 1Z2, Edmonton, Alberta

    Rufus S. Day III

  3. Department of Radiation Oncology, Cross Cancer Institute, T6G 1Z2, Edmonton, Alberta

    Debbie Huyser-Wierenga, Dorcas S. Fulton & R. C. Urtasun

  4. Division of Neurosurgery, Faculty of Medicine, University of Alberta, T6G 2G3, Edmonton, Alberta, Canada

    John D. S. McKean, Kenneth C. Petruk, Peter B. R. Allen, Keith E. Aronyk & Bryce K. A. Weir

Authors
  1. M. Joan Allalunis-Turner
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  2. Rufus S. Day III
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  3. John D. S. McKean
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  4. Kenneth C. Petruk
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  5. Peter B. R. Allen
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  6. Keith E. Aronyk
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  7. Bryce K. A. Weir
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  8. Debbie Huyser-Wierenga
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  9. Dorcas S. Fulton
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  10. R. C. Urtasun
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Allalunis-Turner, M.J., Day, R.S., McKean, J.D.S. et al. Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells. J Neuro-Oncol 11, 157–164 (1991). https://doi.org/10.1007/BF02390175

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