Skarsgard L D, Skwarchuk M W, Wouters B G, Durand R E
Department of Medical Biophysics, British Columbia Cancer Research Centre, Vancouver, Canada.
Radiat Res. 1996 Oct;146(4):388-98.
In earlier studies using asynchronously growing Chinese hamster cells, we observed substructure in the survival response at low doses. The substructure appeared to result from subpopulations of cells having different, cell cycle phase-dependent radiosensitivity. We have now applied the same flow cytometry and cell sorting technique to accurately measure the responses of cells of eight different asynchronously growing human tumor cell lines, representing a wide range in radiosensitivity. When the data were fitted with a linear-quadratic (LQ) function, most of these lines showed substructure similar to that observed in Chinese hamster cells, with the result that values of alpha and beta were dependent on the dose range used for fitting. Values of alpha describing the low-dose response were typically smaller (by as much as 2.2 times) than the alpha describing the high-dose response, while values of beta were larger at low doses. Values of alpha/beta from our measurements are in reasonable agreement with other values published recently if we fit the data for the high-dose range (excluding, for example, 0-4 Gy), which corresponds to a conventional survival response measurement. However, the values of alpha/beta describing the low-dose range were, on average, 2.8-fold smaller. The results show that the usual laboratory measurement of cell survival over 2 or 3 logs of cell killing, if fitted with a single LQ function, will yield alpha and beta values which may give a rather poor description of cell inactivation at low dose in asynchronous cells, no matter how carefully those measurements are done, unless the low-dose range is fitted separately. The contribution of killing represented by the beta coefficient at low doses was found to be surprisingly large, accounting for 40-70% of cell inactivation at 2 Gy in these cell lines. A two-population LQ model provides excellent fits to the data for most of the cell lines though, as one might expect with a five-parameter model, the best-fitting value of the various parameters is far from unique, and the values are probably not reliable indicators of the size and radiosensitivity of the different cell subpopulations. At very low dose, below 0.5-1 Gy, another order of substructure is observed: the hypersensitive response; this is described in the accompanying paper (Wouters et al., Radiat. Res. 146, 399-413, 1996).
在早期使用异步生长的中国仓鼠细胞进行的研究中，我们观察到低剂量下存活反应的亚结构。这种亚结构似乎是由具有不同细胞周期阶段依赖性放射敏感性的细胞亚群导致的。我们现在应用相同的流式细胞术和细胞分选技术，准确测量了八种不同的异步生长的人类肿瘤细胞系的细胞反应，这些细胞系代表了广泛的放射敏感性范围。当数据用线性二次（LQ）函数拟合时，这些细胞系中的大多数显示出与在中国仓鼠细胞中观察到的类似的亚结构，结果是α和β值取决于用于拟合的剂量范围。描述低剂量反应的α值通常比描述高剂量反应的α值小（多达2.2倍），而β值在低剂量时较大。如果我们拟合高剂量范围（例如，不包括0 - 4 Gy）的数据，这对应于传统的存活反应测量，我们测量的α/β值与最近发表的其他值合理一致。然而，描述低剂量范围的α/β值平均小2.8倍。结果表明，如果用单个LQ函数拟合，通常在2或3个对数级细胞杀伤范围内进行的细胞存活实验室测量，将产生α和β值，这些值可能对异步细胞在低剂量下的细胞失活描述得相当差，无论这些测量多么仔细，除非单独拟合低剂量范围。发现低剂量下由β系数表示的杀伤贡献惊人地大，在这些细胞系中占2 Gy时细胞失活的40 - 70%。双群体LQ模型对大多数细胞系的数据提供了很好的拟合，不过，正如人们可能对五参数模型所预期的那样，各种参数的最佳拟合值远非唯一，并且这些值可能不是不同细胞亚群大小和放射敏感性的可靠指标。在非常低的剂量下，低于0.5 - 1 Gy，观察到另一种亚结构顺序：超敏反应；这在随附的论文中描述（Wouters等人，Radiat. Res. 146, 399 - 413, 1996）。
