Skip to main content

Rate of buthionine sulfoximine entry into brain and xenotransplanted human gliomas.

Publication ,  Journal Article
Fekete, I; Griffith, OW; Schlageter, KE; Bigner, DD; Friedman, HS; Groothuis, DR
Published in: Cancer Res
February 15, 1990

Buthionine sulfoximine (BSO) is an inhibitor of glutathione synthesis and can be used to potentiate the effects of chemotherapeutic alkylating agents and radiotherapy. We examined the rates of influx and efflux of [35S]BSO administered to athymic mice with and without xenografted D-54MG human gliomas. Three analytic approaches were applied to the experimental data to obtain values of the blood-to-tissue influx constant, K1, of BSO. Multiple time point experiments in tumor-bearing mice were analyzed with a two-compartment model and nonlinear fitting routines, and by graphical analysis which assumed no backflux of BSO from tissue to blood. A third approach used single time point data in nontumor-bearing mice and assumed no backflux. Calculated values of the K1 of BSO ranged from 0.23 to 1.35 microliters/g/min in tumor-free cortex, and from 5.3 to 6.3 microliters/g/min in the D-54MG gliomas. The tissue-to-blood efflux constant, k2, was zero in both cortex and tumor, suggesting that BSO entered cells and was trapped once it crossed the blood-brain barrier. Estimates of plasma vascular space (Vp) ranged from 2 to 20 microliters/g in cortex, and from 103 to 169 microliters/g in tumor. Another set of experiments, done in normal mice with different doses of BSO, suggested that BSO competes for neutral amino acid transport sites at the blood-brain barrier, but that the capacity of the carrier-mediated transport system is low and saturates at administered doses of about 0.5 mmol/kg (corresponding to plasma concentrations of about 12 mumol/ml). The rate of entry into brain was proportional to the octanol/water partition coefficient and molecular weight of BSO, which also supports passive diffusion as the means of entry. Consequently, although the rate of BSO entry into D-54MG gliomas was between 4 and 30 times higher than the rate of entry into tumor-free cortex, the results of these experiments suggest that most of the BSO that enters brain tumors in the doses commonly used in experimental situations will cross capillaries by passive diffusion.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

February 15, 1990

Volume

50

Issue

4

Start / End Page

1251 / 1256

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Methionine Sulfoximine
  • Humans
  • Glioma
  • Diffusion
  • Capillaries
  • Buthionine Sulfoximine
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fekete, I., Griffith, O. W., Schlageter, K. E., Bigner, D. D., Friedman, H. S., & Groothuis, D. R. (1990). Rate of buthionine sulfoximine entry into brain and xenotransplanted human gliomas. Cancer Res, 50(4), 1251–1256.
Fekete, I., O. W. Griffith, K. E. Schlageter, D. D. Bigner, H. S. Friedman, and D. R. Groothuis. “Rate of buthionine sulfoximine entry into brain and xenotransplanted human gliomas.Cancer Res 50, no. 4 (February 15, 1990): 1251–56.
Fekete I, Griffith OW, Schlageter KE, Bigner DD, Friedman HS, Groothuis DR. Rate of buthionine sulfoximine entry into brain and xenotransplanted human gliomas. Cancer Res. 1990 Feb 15;50(4):1251–6.
Fekete, I., et al. “Rate of buthionine sulfoximine entry into brain and xenotransplanted human gliomas.Cancer Res, vol. 50, no. 4, Feb. 1990, pp. 1251–56.
Fekete I, Griffith OW, Schlageter KE, Bigner DD, Friedman HS, Groothuis DR. Rate of buthionine sulfoximine entry into brain and xenotransplanted human gliomas. Cancer Res. 1990 Feb 15;50(4):1251–1256.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

February 15, 1990

Volume

50

Issue

4

Start / End Page

1251 / 1256

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Methionine Sulfoximine
  • Humans
  • Glioma
  • Diffusion
  • Capillaries
  • Buthionine Sulfoximine