Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells.
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/10(6) 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.
Allalunis-Turner
M J
MJ
Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
Day
R S
RS
McKean
J D
JD
Petruk
K C
KC
Allen
P B
PB
Aronyk
K E
KE
Weir
B K
BK
Huyser-Wierenga
D
D
Fulton
D S
DS
Urtasun
R C
RC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019328:Buthionine Sulfoximine; D002330:Carmustine / Q000627:therapeutic use; D002648:Child; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008297:Male; D008466:Mechlorethamine / Q000627:therapeutic use; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008466:Mechlorethamine; D005978:Glutathione; D002330:Carmustine