Hill A A, Skarsgard L D
Department of Medical Biophysics, BC Cancer Research Centre, Vancouver, British Columbia, Canada.
Int J Radiat Biol. 1999 Nov;75(11):1409-20. doi: 10.1080/095530099139278.
To determine whether some of the deviations from the simple linear-quadratic (LQ) theory in the radiation dose survival responses of asynchronous cultures of human tumour cell lines are caused by the presence of cell-age specific subpopulations which all individually follow LQ theory, but have different radiosensitivities.
Human tumour cells were synchronized by mitotic selection and their survival dose responses were measured at doses from 0.05 Gy to 12 Gy, using a high-precision survival assay. These responses were compared with a kinetic model of radiation survival in synchronized cells, which assumed that age-specific populations individually obeyed the LQ theory. The cell lines used included HT-29 and A549, which have typical dose responses, and U1, which is somewhat atypical.
In two of the three cell lines, A549 and HT-29, observed deviations from the LQ model were consistent with those expected from cell-age heterogeneity. In the third cell line, U1, survival responses could not be described by the LQ theory, even when cell-age heterogeneity was considered.
The LQ model provided an adequate description of cell survival for two of three tumour cell lines in this study when cell-age related heterogeneity in survival responses was accounted for. However, some alternative survival models (such as the repair saturation model) provided better characterizations of the survival response of the third cell line and, in fact, gave good descriptions of survival for all three cell lines.
确定人类肿瘤细胞系异步培养物辐射剂量存活反应中与简单线性二次(LQ)理论的某些偏差是否由细胞年龄特异性亚群的存在引起,这些亚群各自都遵循LQ理论,但具有不同的放射敏感性。
通过有丝分裂选择使人类肿瘤细胞同步化,并使用高精度存活测定法在0.05 Gy至12 Gy的剂量下测量其存活剂量反应。将这些反应与同步化细胞中辐射存活的动力学模型进行比较,该模型假设年龄特异性群体各自遵循LQ理论。所使用的细胞系包括具有典型剂量反应的HT-29和A549,以及有点非典型的U1。
在三个细胞系中的两个,即A549和HT-29中,观察到的与LQ模型的偏差与细胞年龄异质性预期的偏差一致。在第三个细胞系U1中,即使考虑了细胞年龄异质性,存活反应也不能用LQ理论来描述。
当考虑到存活反应中与细胞年龄相关的异质性时,LQ模型对本研究中三个肿瘤细胞系中的两个细胞系的细胞存活提供了充分的描述。然而,一些替代的存活模型(如修复饱和模型)对第三个细胞系的存活反应提供了更好的表征,并且实际上对所有三个细胞系的存活都给出了很好的描述。