The tissue level of dexamethasone in human brain tumors is about 1000 times lower than the cytotoxic concentration in cell culture.
In glioblastoma patients dexamethasone is routinely administered as an antiedematous drug. In contrast to its empirically proven effect, the biochemical way of action remains poorly understood. In order to assess whether a direct cytotoxic effect is present in vivo we compared dexamethasone levels in brain tumor specimens with its cytotoxic concentrations in cell culture. Biopsy specimens were taken during microsurgical tumor removal, homogenized and dexamethasone levels were measured by high pressure liquid chromatography. In cell culture we tested different concentrations of dexamethasone on A172, U87, U373 cells and on eleven primary glioblastoma cell lines. Furthermore a pilocytic astrocytoma I, an astrocytoma II and an oligodendroglioma III and a meningioma were examined. Cell viability was assessed using the Alamar Blue assay and the concentrations resulting in loss of 50% of the cell population were calculated (LD50). The average brain tumor tissue concentration of dexamethasone was 225 nanogram g(-1). The mean LD50 in cell culture ranged at 222 microgram ml(-1). We conclude that a direct cytotoxic effect of dexamethasone on brain tumor cells is not present in vivo because the tissue levels of the drug are about 1000 times lower than the LD50 in cell culture.
Department of Neurosurgery, Justus Liebig University, Giessen, Germany. ulf.nestler@neuro.med.uni-giessen.de
Ulf
U
Nestler
Michael
M
Winking
Dieter-Karsten
DK
Böker
D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics / Q000633:toxicity*; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D003907:Dexamethasone / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007928:Lethal Dose 50; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D003907:Dexamethasone