Determination of the lethal dose of dexamethasone for early passage in vitro human glioblastoma cell cultures.
Previous investigators have supported the idea that glucocorticoids may be oncolytic. In this study, the percentage of cell death in two human glioblastoma cell cultures was related to the concentration of dexamethasone that was administered. It was determined that for Cell line 1, the median lethal dose was approximately 500-800 micrograms/ml and the completely lethal dose was about 900-1000 micrograms/ml; the 3H-thymidine uptake to approximate the mitotic rate was 16,607 cpm, and the dexamethasone receptor activity was 228 fmol/mg protein. The median lethal dose and completely lethal dose for Cell line 2 was approximately 500-600 micrograms/ml and 700-1000 micrograms/ml, respectively; the 3H-thymidine uptake was 8402 cpm, and the dexamethasone receptor activity was 137 fmol/mg protein. These lethal concentrations of dexamethasone are probably higher than can be tolerated by systemic delivery. However, it remains to be seen whether the interstitial administration of dexamethasone could achieve local concentrations resulting in the oncolysis of malignant gliomas. The clinical significance of these findings will depend on the local tolerance of normal brain parenchyma to very high doses of dexamethasone. A review of some of the literature is included.
Maciunas
R J
RJ
Department of Neurological Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.
Mericle
R A
RA
Sneed
C L
CL
Hefner
D J
DJ
Commers
P A
PA
Kovacs
W J
WJ
D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D011965:Receptors, Glucocorticoid; C028697:dexamethasone receptor; D003907:Dexamethasone