Wouters B G, Sy A M, Skarsgard L D
Department of Medical Biophysics, British Columbia Cancer Research Centre, Vancouver, Canada.
Radiat Res. 1996 Oct;146(4):399-413.
It is well known that cells of human tumor cell lines display a wide range of sensitivity to radiation, at least a part of which can be attributed to different capacities to process and repair radiation damage correctly. We have examined the response to very low-dose radiation of cells of five human tumor cell lines that display varying sensitivity to radiation, using an improved assay for measurement of radiation survival. This assay improves on the precision of conventional techniques by accurately determining the numbers of cells at risk, and has allowed us to measure radiation survival to doses as low as 0.05 Gy. Because of the statistical limitations in measuring radiation survival at very low doses, extensive averaging of data was used to determine the survival response accurately. Our results show that the four most resistant cell lines exhibit a region of initial low-dose hypersensitivity. This hypersensitivity is followed by an increase in radioresistance over the dose range 0.3 to 0.7 Gy, beyond which the response is typical of that seen in most survival curves. Mathematical modeling of the responses suggests that this phenomenon is not due to a small subpopulation of sensitive cells (e.g. mitotic), but rather is a reflection of the induction of resistance in the whole cell population, or at least a significant proportion of the whole cell population. These results suggest that a dose-dependent alteration in the processing of DNA damage over the initial low-dose region of cell survival may contribute to radioresistance in some cell lines.
众所周知，人类肿瘤细胞系的细胞对辐射表现出广泛的敏感性，其中至少一部分可归因于正确处理和修复辐射损伤的不同能力。我们使用一种改进的辐射存活测量方法，研究了五种对辐射敏感性不同的人类肿瘤细胞系的细胞对极低剂量辐射的反应。该方法通过准确确定处于危险中的细胞数量，提高了传统技术的精度，并使我们能够测量低至0.05 Gy剂量的辐射存活率。由于在极低剂量下测量辐射存活存在统计局限性，我们使用了大量数据平均来准确确定存活反应。我们的结果表明，四种最具抗性的细胞系表现出初始低剂量超敏反应区域。这种超敏反应之后是在0.3至0.7 Gy剂量范围内辐射抗性增加，超过该范围后，反应是大多数存活曲线中常见的反应。对这些反应的数学建模表明，这种现象不是由于一小部分敏感细胞（如有丝分裂细胞）引起的，而是整个细胞群体或至少是整个细胞群体的很大一部分中抗性诱导的反映。这些结果表明，在细胞存活的初始低剂量区域，DNA损伤处理的剂量依赖性改变可能导致某些细胞系的辐射抗性。
