Peacock J H, Cassoni A M, McMillan T J, Steel G G
Radiotherapy Research Unit, Institute of Cancer Research, Surrey, U.K.
Int J Radiat Biol. 1988 Dec;54(6):945-53. doi: 10.1080/09553008814552341.
Split-dose studies have been performed on four human tumour cell lines of widely differing radiosensitivity in order to characterize the relationship between cellular recovery and radiation dose. Previous studies using the split-dose experiment have usually measured recovery at a single dose level and assumed an underlying multi-target model of radiation effect. This predicts that the recovery ratio should reach a plateau when the dose used per fraction is beyond the shoulder of the acute survival curve. In contrast, the linear-quadratic model predicts that the recovery ratio will increase steeply as a function of dose and will never reach a plateau. Our results show that recovery increases with increasing dose and therefore no single value of the recovery ratio can be used for comparative purposes. Using these data, we have derived a value for the beta-component of the linear-quadratic model that is independent of alpha. In addition we propose that the beta-parameter derived in this way provides the most satisfactory basis for intercomparison of cellular recovery between cell lines of differing radiosensitivity. Cellular recovery at any given dose was greatest in the most radiosensitive cell line, suggesting that increased radiosensitivity does not result from decreased recovery capacity. The results suggest that cells with steep acute radiation survival curves and which show little split-dose recovery may not be recovery deficient. Consequently, using such cells in attempts to correlate recovery with the underlying molecular processes of radiation damage repair could lead to misleading results.
为了描述细胞修复与辐射剂量之间的关系，对四种放射敏感性差异很大的人类肿瘤细胞系进行了分次剂量研究。以前使用分次剂量实验的研究通常在单一剂量水平测量修复情况，并假定存在一个潜在的多靶辐射效应模型。这预测当每次分割所用剂量超过急性存活曲线的肩部时，修复率应达到一个平台期。相比之下，线性二次模型预测修复率将随着剂量的增加而急剧上升，且永远不会达到平台期。我们的结果表明，修复率随剂量增加而增加，因此不能用单一的修复率值进行比较。利用这些数据，我们得出了线性二次模型中与α无关的β分量的值。此外，我们建议以这种方式得出的β参数为比较不同放射敏感性细胞系之间的细胞修复提供了最令人满意的基础。在任何给定剂量下，放射敏感性最高的细胞系的细胞修复程度最大，这表明放射敏感性增加并非由于修复能力下降所致。结果表明，急性辐射存活曲线陡峭且分次剂量修复很少的细胞可能并非修复缺陷。因此，使用这类细胞试图将修复与辐射损伤修复的潜在分子过程相关联可能会导致误导性结果。
