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2'-2'二氟脱氧胞苷(dFdC,吉西他滨)对两种内在放射敏感性不同的人头颈部鳞状癌细胞系辐射诱导细胞杀伤的影响。

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.

作者信息

Rosier J F, Beauduin M, Bruniaux M, de Bast M, de Coster B, Octave-Prignot M, Scalliet P, Grégoire V

机构信息

UCL St-Luc University Hospital, Department of Radiation Oncology, Brussels, Belgium.

出版信息

Int J Radiat Biol. 1999 Feb;75(2):245-51. doi: 10.1080/095530099140708.

DOI:10.1080/095530099140708
PMID:10072186
Abstract

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 (0-12Gy). Cell survival curves were corrected for the toxicity of the drug alone.

RESULTS

In both cell lines, radio-enhancement was observed with 5 microM 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 alpha term of the linear-quadratic model. In SQD9 cells, radio-enhancement increased with dFdC incubation time. At 24h, DMF reached a value of 1.5 (95% CI 0.9-3.2). In SCC61 cells at 24h, 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 microM from which values it levelled off up to 100 microM.

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 radio-resistant 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 microM.

摘要

目的

本研究调查了吉西他滨(dFdC)对两种具有不同内在细胞放射敏感性的头颈部鳞状细胞癌的体外放射增敏作用。

材料与方法

使用放射敏感的(SCC61,SF2 = 0.16)和放射抗性的(SQD9,SF2 = 0.49)人源头颈部鳞状细胞癌。汇合的细胞与dFdC一起孵育,然后在无药物培养基中用单剂量250 kV X射线(0 - 12 Gy)照射。细胞存活曲线针对单独药物的毒性进行了校正。

结果

在两种细胞系中,在照射前用5 microM dFdC孵育3小时均观察到放射增敏作用。对于SQD9和SCC61细胞,在存活分数水平为0.5时的剂量修正因子(DMF)分别达到1.3(95%可信区间1.1 - 1.6)和1.5(95%可信区间1.4 - 1.5)。放射增敏与线性二次模型的α项适度增加有关。在SQD9细胞中,放射增敏随dFdC孵育时间增加。在24小时时,DMF达到1.5(95%可信区间0.9 - 3.2)。在SCC61细胞中24小时时,DMF达到1.1(95%可信区间0.9 - 1.2)。在两种细胞系中,放射增敏随dFdC浓度增加至5 - 10 microM,此后直至100 microM其值趋于平稳。

结论

数据表明dFdC在两种细胞系中均诱导了适度的放射增敏作用。对于短孵育时间,dFdC并未优先对放射抗性更强的细胞产生放射增敏作用,而对于较长时间则观察到相反情况。在两种细胞系中,dFdC浓度高于5 - 10 microM时放射增敏作用达到饱和。

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