Radiation enhancement of gemcitabine in two human squamous cell carcinoma cell lines.
BACKGROUND
Gemcitabine (dFdC) is a new nucleoside analogue with promising activity in different solid tumors. We investigated whether dFdC enhances the effect of irradiation in human squamous carcinoma cells of the oropharynx (#4197) and of the uterine cervix (HeLa) with special regard to the time-dose-relationship concerning dFdC and the dependence upon the timing of irradiation.


METHODS
Under standardized conditions monolayers of cells were exposed to various dFdC concentrations (0.003-10 mumol/l) for different times (4-24 h). Irradiation (0-6 Gy) followed immediately or 12 h after dFdC exposure (0.003-0.03 mumol/l; 4-24 h).


RESULTS
The cytotoxic effect of dFdC depends on its concentration and the exposure duration. Exposed to non and/or slightly cytotoxic concentrations (> or = 0.003-0.03 mumol/l) for 4, 8, 16 and 24 h and followed by immediate irradiation the radiation enhancement ratio (RER) is 1.03-1.67 in #4197 cells and 1.04-2.47 in HeLa cells, respectively. Irradiated 12 h after 24 h exposure (dFdC 0.01-0.03 mumol/l) the RER is reduced to 1.10-1.17 (#4197) and 1.18-1.72 (HeLa).


CONCLUSIONS
Depending on the drug concentration, exposure duration, and timing of irradiation, dFdC enhances the irradiation effect on human squamous cell carcinoma cell lines (#4197, HeLa).
Mose
S
S
Department of Radiotherapy, Johann Wolfgang Goethe-Universität, Frankfurt/Main, Germany.
Karapetian
M
M
Jüling-Pohlit
L
L
Taborski
B
B
Damrau
M
M
Ramm
U
U
Rahn
A
A
Böttcher
H D
HD
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D009959:Oropharyngeal Neoplasms / Q000473:pathology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014410:Tumor Stem Cell Assay; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine