Survival of human glioma cells treated with various combination of temozolomide and X-rays.
OBJECTIVE
To investigate the effect of temozolomide, a 3-methyl derivative of mitozolomide in combination with X-rays in human glioma-derived cell lines.


METHODS
Glioma cell lines D384 and U251 were treated with temozolomide for various periods of time in combinations with X-rays. Temozolomide administration was repeated every 24 h for exposures up to 96 h. Cytotoxicity was determined with a clonogenic assay.


RESULTS
Incubation of D384 cells with temozolomide during 24 h prior to or following irradiation results in a moderate enhancement of the cytotoxicity. Prolonged treatment with temozolomide, i.e., 48-96 h before X-rays, causes a stronger potentiation. In contrast, no enhancement is observed in irradiated U251 cells in combination with 24-96 h temozolomide treatment. In addition to single-dose irradiation, we investigated the effect of temozolomide in D384 cells with concomitant fractionated irradiation. A 96-h exposure to temozolomide with simultaneous doses of 2 Gy X-rays at 24-h intervals, causes a significant further reduction in cell survival as compared to fractionated irradiation only.


CONCLUSIONS
Depending on the cell line, treatment of glioma cells with temozolomide and X-rays can have either an additional effect or potentiate cell killing.
van Rijn
J
J
Department of Radiation Oncology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands. radbiol@med.vu.nl
Heimans
J J
JJ
van den Berg
J
J
van der Valk
P
P
Slotman
B J
BJ
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D000077204:Temozolomide; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014410:Tumor Stem Cell Assay
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide