The effect of 2′-2′ difluorodeoxycytidine (dFdC, gemcitabine) on radiation-induced cell lethality in two human head and neck squamous carcinoma cell lines differing in intrinsic radiosensitivity

Purpose: The present study investigated in vitro radio-enhancement by gemcitabine (dFdC) in two head and neck squamous cell carcinomas with different intrinsic cellular radiosensitivity. Materials and methods: Radiosensitive (SCC61, SF2=0.16) and radioresistant (SQD9, SF2 = 0.49) human head and neck squamous cell carcinomas were used. Confluent cells were incubated with dFdC and irradiated in drug-free medium with a single dose of 250 kV X-rays (0-12 Gy). Cell survival curves were corrected for the toxicity of the drug alone. Results: In both cell lines, radio-enhancement was observed with 5 mu M dFdC incubated for 3 h prior to irradiation. Dose modification factors (DMF) at a surviving fraction level of 0.5 reached 1.3 (95% CI 1.1-1.6) and 1.5 (95% CI 1.4-1.5) for SQD9 and SCC61 cells, respectively. Radio-enhancement was associated with a modest increase in the a term of the linear-quadratic model. In SQD9 cells, radio-enhancement increased with dFdC incubation time. At 24 h, DMF reached a value of 1.5 (95% CI 0.9-3.2). In SCC61 cells at 24 h, DMF reached a value of 1.1 (95% CI 0.9-1.2). In both cell lines, radio-enhancement increased with dFdC concentration up to 5-10 mu M from which values it levelled off up to 100 mu M. Conclusions: The data indicated that dFdC induced a modest radio-enhancement in both cell lines. For a short incubation time, dFdC did not radio-enhance preferentially the more radioresistant cells, whereas the opposite was observed for a longer time. In both cell lines, radio-enhancement was saturated above a dFdC concentration of 5-10 mu M.