Skarsgard L D, Skwarchuk M W, Wouters B G
Department of Medical Biophysics, British Columbia Cancer Research Centre, Vancouver, Canada.
Radiat Res. 1994 Apr;138(1 Suppl):S72-5.
We have observed that when a single linear-quadratic (LQ) function is used to fit the radiation survival response of an asynchronously dividing population of V79 cells, a consistent misfit occurs at low doses. The data can be better described by fitting the low-dose and high-dose ranges separately, and there is evidence of a two-component response. The most obvious explanation is that we may simply be seeing the response of subpopulations of cells of different radiosensitivity: sensitive G1-, G2- and M-phase cells and resistant S-phase cells. The cell sorting assay for cell survival which we have used in these studies may thus be providing sufficient accuracy to resolve these subpopulations, not previously seen in conventional survival measurements. An alternative explanation is that the linear-quadratic function may be inappropriate for accurate description of the radiation survival response at low dose, at least for these cells. To test this hypothesis we have used three other models to fit the data: the single-hit plus multi-target (SHMT) model and the two-parameter repair-misrepair (RMR) model both yielded inferior fits to the asynchronous survival data; the three-parameter RMR model provided an improved fit to the data. The best fit, however, was obtained using a two-population LQ model, which suggested approximately equal numbers of sensitive and resistant cells. When the survival response of tightly synchronized G1/S-phase cells was measured using the cell sorting assay, no substructure was observed. This offers strong support to the hypothesis that the substructure observed in the asynchronous survival response is due to subpopulations of cells of different, cycle-dependent radiosensitivity.
我们观察到，当使用单个线性二次（LQ）函数来拟合异步分裂的V79细胞群体的辐射存活响应时，在低剂量下会出现一致的拟合不佳情况。通过分别拟合低剂量和高剂量范围，可以更好地描述数据，并且有证据表明存在双组分响应。最明显的解释是，我们可能只是看到了不同放射敏感性细胞亚群的响应：敏感的G1期、G2期和M期细胞以及抗性的S期细胞。我们在这些研究中使用的细胞存活细胞分选测定法可能因此提供了足够的准确性来分辨这些亚群，而这在传统的存活测量中以前未曾见过。另一种解释是，线性二次函数可能不适用于准确描述低剂量下的辐射存活响应，至少对于这些细胞是这样。为了检验这一假设，我们使用了其他三种模型来拟合数据：单击中加多靶（SHMT）模型和双参数修复-错配（RMR）模型对异步存活数据的拟合都较差；三参数RMR模型对数据的拟合有所改善。然而，使用双群体LQ模型获得了最佳拟合，这表明敏感细胞和抗性细胞的数量大致相等。当使用细胞分选测定法测量紧密同步的G1/S期细胞的存活响应时，未观察到亚结构。这为以下假设提供了有力支持，即在异步存活响应中观察到的亚结构是由于具有不同的、依赖于周期的放射敏感性的细胞亚群所致。
