Increased Melphalan Activity in Intracranial Human Medulloblastoma and Glioma Xenografts Following Buthionine Sulfoximine-Mediated Glutathione Depletion

Abstract
In previous studies we demonstrated that administration of buthionine sulf-oximine (BSO) to athymic BALB/cmice bearing intracranial human gli-oma xenografts resulted in highly se-lective depletion of glutathione in neo-plastic tissue with minimal effects on contralateral normal brain tissue. In the present study we treated athymic BALB/c mice bearing intracranial human glioma (D-54 MG) or medul-loblastoma (TE-671) xenografts with melphalan alone or BSO followed by melphalan. Administration of BSO depleted intracellular glutathione to7.5% of the control level. BSO plusmelphalan resulted in a significant increase in median survival over that produced by melphalan alone: 45.3%versus 26.4% in TE-671 and 69%versus 27.6 in D-54 MG. These studies justify further efforts to modulate chemotherapeutic and radio-therapeutic interventions of primarymalignant brain tumors by depletionof glutathione. [J Natl Cancer Inst81:524-527, 1989]

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