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Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells
Authors:M. Joan Allalunis-Turner  Rufus S. Day III  John D. S. McKean  Kenneth C. Petruk  Peter B. R. Allen  Keith E. Aronyk  Bryce K. A. Weir  Debbie Huyser-Wierenga  Dorcas S. Fulton  R. C. Urtasun
Affiliation:(1) Radiobiology Laboratory, Department of Radiation Oncology, Cross Cancer Institute, T6G 1Z2 Edmonton, Alberta;(2) Molecular Genetics and Carcinogenesis Laboratory, Department of Medicine, Cross Cancer Institute, T6G 1Z2 Edmonton, Alberta;(3) Department of Radiation Oncology, Cross Cancer Institute, T6G 1Z2 Edmonton, Alberta;(4) Division of Neurosurgery, Faculty of Medicine, University of Alberta, T6G 2G3 Edmonton, Alberta, Canada;(5) Radiobiology, Cross Cancer Institute, 11560 University Avenue, T6G 1Z2 Edmonton, Alberta, Canada
Abstract: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.
Keywords:glutathione  malignant glioma  buthionine sulfoximine  MTT assay  chemosensitization
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