Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts.
Published
Journal Article
D-54 MG, a human glioma-derived continuous cell line growing as subcutaneous or intracranial xenografts in athymic mice, was found to be sensitive to the effects of D,L-buthionine-(SR)-sulfoximine, a selective inhibitor of gamma-glutamylcysteine synthetase. Intraperitoneal administration of one dose of buthionine sulfoximine (BSO, 5 mmol/kg) resulted in depletion of total intracellular glutathione to 57 and 47% of control 12 hr, and 73 and 23% of control 24 hr, after BSO in subcutaneous and intracranial xenografts respectively. Concurrent measurement of total glutathione in the contralateral (non-tumor-containing) cerebral hemisphere in mice bearing intracranial D-54 xenografts demonstrated insignificant depletion of glutathione. Multiple doses of BSO, at 12-hr intervals, resulted in further depletion to 27% (s.c.) and 16.5% (i.c.) of control 12 hr following the final dose of BSO. Quantitative analysis of BSO delivery to xenograft and contralateral brain tissue revealed transfer constants, K1, of 15.8-24.1 x 10(-3) and 2.4 x 10(-3) ml.g-1.min-1 for xenograft and "normal" brain respectively. This highly selective depletion of glutathione in neoplastic tissue versus surrounding non-neoplastic host tissue may have therapeutic implications for the rational use of chemotherapeutic and radiotherapeutic intervention.
Full Text
Duke Authors
Cited Authors
- Skapek, SX; Colvin, OM; Griffith, OW; Groothuis, DR; Colapinto, EV; Lee, Y; Hilton, J; Elion, GB; Bigner, DD; Friedman, HS
Published Date
- November 15, 1988
Published In
Volume / Issue
- 37 / 22
Start / End Page
- 4313 - 4317
PubMed ID
- 3196356
Pubmed Central ID
- 3196356
International Standard Serial Number (ISSN)
- 0006-2952
Digital Object Identifier (DOI)
- 10.1016/0006-2952(88)90612-0
Language
- eng
Conference Location
- England