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Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts.

Publication ,  Journal Article
Skapek, SX; Colvin, OM; Griffith, OW; Groothuis, DR; Colapinto, EV; Lee, Y; Hilton, J; Elion, GB; Bigner, DD; Friedman, HS
Published in: Biochem Pharmacol
November 15, 1988

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.

Duke Scholars

Published In

Biochem Pharmacol

DOI

ISSN

0006-2952

Publication Date

November 15, 1988

Volume

37

Issue

22

Start / End Page

4313 / 4317

Location

England

Related Subject Headings

  • Transplantation, Heterologous
  • Pharmacology & Pharmacy
  • Mice, Inbred BALB C
  • Mice
  • Methionine Sulfoximine
  • Male
  • Humans
  • Glutathione
  • Glioma
  • Female
 

Citation

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Skapek, S. X., Colvin, O. M., Griffith, O. W., Groothuis, D. R., Colapinto, E. V., Lee, Y., … Friedman, H. S. (1988). Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts. Biochem Pharmacol, 37(22), 4313–4317. https://doi.org/10.1016/0006-2952(88)90612-0
Skapek, S. X., O. M. Colvin, O. W. Griffith, D. R. Groothuis, E. V. Colapinto, Y. Lee, J. Hilton, G. B. Elion, D. D. Bigner, and H. S. Friedman. “Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts.Biochem Pharmacol 37, no. 22 (November 15, 1988): 4313–17. https://doi.org/10.1016/0006-2952(88)90612-0.
Skapek SX, Colvin OM, Griffith OW, Groothuis DR, Colapinto EV, Lee Y, et al. Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts. Biochem Pharmacol. 1988 Nov 15;37(22):4313–7.
Skapek, S. X., et al. “Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts.Biochem Pharmacol, vol. 37, no. 22, Nov. 1988, pp. 4313–17. Pubmed, doi:10.1016/0006-2952(88)90612-0.
Skapek SX, Colvin OM, Griffith OW, Groothuis DR, Colapinto EV, Lee Y, Hilton J, Elion GB, Bigner DD, Friedman HS. Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts. Biochem Pharmacol. 1988 Nov 15;37(22):4313–4317.
Journal cover image

Published In

Biochem Pharmacol

DOI

ISSN

0006-2952

Publication Date

November 15, 1988

Volume

37

Issue

22

Start / End Page

4313 / 4317

Location

England

Related Subject Headings

  • Transplantation, Heterologous
  • Pharmacology & Pharmacy
  • Mice, Inbred BALB C
  • Mice
  • Methionine Sulfoximine
  • Male
  • Humans
  • Glutathione
  • Glioma
  • Female