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人类肿瘤细胞的内在放射抗性会被辐射诱导产生吗?

Might intrinsic radioresistance of human tumour cells be induced by radiation?

作者信息

Lambin P, Malaise E P, Joiner M C

机构信息

Gray Laboratory, Mount Vernon Hospital, Northwood, UK.

出版信息

Int J Radiat Biol. 1996 Mar;69(3):279-90. doi: 10.1080/095530096145832.

DOI:10.1080/095530096145832
PMID:8613677
Abstract

Survival measurements were made on six human tumour cell lines in vitro after irradiation with single doses of X rays. Doses up to 5 Gy were used giving surviving fractions down to 20%, but the majority of the measurements were made at doses < 1 Gy. These six cell lines have very different intrinsic radiosensitivities: HT29, Be11, and RT112 are radioresistant with surviving fractions at 2 Gy (SF2) between 60 and 74%, while MeWo, SW48, and HX142 are radiosensitive (SF2 = 3-29%). For all the cell lines, response over the dose range 2-5 Gy showed a good fit to a Linear-Quadratic (LQ) model. However, HT29, Be11, and RT112 cells showed a significant increase in X-ray radiosensitivity at doses below < 1 Gy compared with the prediction extrapolated from a LQ model fitted to the data at higher doses. The LQ model also slightly underpredicted the effect of low-dose X rays in MeWo cells, but the response of SW48 and HX142 cells was well described by the LQ model at all doses, with no evidence of increased low-dose effectiveness. The most plausible explanation for this phenomenon is that it reflects an induced radioresistance so that low doses of X-rays in vitro are more effective per Gy than higher doses, because only at higher doses is there sufficient damage to trigger repair systems or other radioprotective mechanisms. It follows that variation in the amount of inducible radioresistance might explain, in part, differences in intrinsic radiosensitivity above > 1 Gy between cell lines: cells would be intrinsically radiosensitive because they have a diminished inducible response.

摘要

用单剂量X射线照射六种人类肿瘤细胞系后,在体外进行存活测量。使用的剂量高达5 Gy,使存活分数低至20%,但大多数测量是在剂量<1 Gy时进行的。这六种细胞系具有非常不同的内在放射敏感性:HT29、Be11和RT112具有放射抗性,2 Gy时的存活分数(SF2)在60%至74%之间,而MeWo、SW48和HX142具有放射敏感性(SF2 = 3-29%)。对于所有细胞系,2-5 Gy剂量范围内的反应与线性二次(LQ)模型拟合良好。然而,与根据高剂量数据拟合的LQ模型外推预测相比,HT29、Be11和RT112细胞在剂量低于<1 Gy时X射线放射敏感性显著增加。LQ模型也略微低估了低剂量X射线对MeWo细胞的影响,但SW48和HX142细胞在所有剂量下的反应都能很好地用LQ模型描述,没有低剂量有效性增加的证据。对此现象最合理的解释是,它反映了一种诱导的放射抗性,因此体外低剂量X射线每Gy比高剂量更有效,因为只有在高剂量时才有足够的损伤触发修复系统或其他放射防护机制。由此可见,诱导放射抗性量的变化可能部分解释了细胞系之间>1 Gy时内在放射敏感性的差异:细胞内在放射敏感是因为它们的诱导反应减弱。

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