van den Aardweg G J, Hopewell J W, Guttenberger R
Research Institute (University of Oxford), Churchill Hospital, United Kingdom.
Radiat Res. 1996 May;145(5):586-94.
The kinetics of the repair of radiation-induced sublethal damage (SLD) was studied for the epidermis of the pig. A total of either 7 or 14 interfraction intervals with incomplete repair was achieved by giving 28 fractions either as 7 x 2 fractions/day plus a top-up dose of 17 Gy (half tolerance) or as 14 x 2 fractions/day. The dose per fraction ranged from 1.96-4.82 Gy. A total of 9 intervals ranging from 0.17 h up to 8 h between fractions was used. The incidence of moist desquamation, as an estimate of acute epidermal response, was used as an end point to establish dose-effect relationships. The data were analyzed using either the incomplete repair model of Thames, assuming mono-exponential repair kinetics, or a modified version of the incomplete repair model, assuming bi-exponential repair of sublethal damage. Both methods of analysis allowed for the longer overnight interval between fractions. Analysis assuming mono-exponential repair gave a T1/2 of 0.74 h for the combined data, although there was a trend toward a longer half-time when only the longer interfraction intervals ( > 1.0 h) were used in the analysis. A further analysis using the modified version of an incomplete repair model gave a fast and a slow component of repair with significantly different half-times of 0.09 and 4.5 h, respectively. Varying the number of incomplete repair intervals by replacing half the number of fractions with a single half-tolerance top-up dose did not modify the kinetics of repair significantly, in terms of either the repair half-times or the proportion of repair associated with a fast and slow component. Reanalysis of data published previously for 3 and 4 fractions using the modified incomplete repair model again resulted in two components of repair, represented by the significantly different half-times of 0.17 and 3.0 h. These values were similar to those obtained from the multiple-fraction experiment. These data clearly demonstrate that an acutely responding tissue is associated with a long T1/2 for the repair of SLD which is independent of the dose per fraction. For accelerated fractionation schedules in the clinic, using multiple fractions per day, these results suggest a need to control the intervals between fractions carefully and when appropriate to reduce the total dose to avoid serious normal-tissue complications.
对猪的表皮进行了辐射诱导亚致死损伤（SLD）修复动力学的研究。通过给予28次分割剂量，实现了7个或14个分割间期的不完全修复，分割方式为7×2次/天加17 Gy的补充剂量（半耐受剂量）或14×2次/天。每次分割剂量范围为1.96 - 4.82 Gy。分割之间的间隔时间共有9种，从0.17小时到8小时不等。以湿性脱屑的发生率作为急性表皮反应的评估指标，以此作为建立剂量 - 效应关系的终点。使用泰晤士河不完全修复模型（假设单指数修复动力学）或不完全修复模型的修正版本（假设亚致死损伤的双指数修复）对数据进行分析。两种分析方法都考虑了分割之间较长的夜间间隔。假设单指数修复进行分析时，合并数据的T1/2为0.74小时，不过当仅在分析中使用较长的分割间期（>1.0小时）时，有半时间延长的趋势。使用不完全修复模型的修正版本进行的进一步分析得出了快速和慢速两个修复成分，其半时间分别为0.09小时和4.5小时，差异显著。通过用单次半耐受补充剂量替代一半的分割次数来改变不完全修复间期的数量，在修复半时间或与快速和慢速成分相关的修复比例方面，均未显著改变修复动力学。使用修正的不完全修复模型对先前发表的3次和4次分割的数据重新分析，再次得到两个修复成分，其半时间分别为0.17小时和3.0小时，差异显著。这些值与多分割实验得到的值相似。这些数据清楚地表明，急性反应组织在修复SLD时具有较长的T1/2，且与每次分割剂量无关。对于临床中的加速分割方案，即每天使用多次分割，这些结果表明需要仔细控制分割之间的间隔时间，并在适当的时候降低总剂量，以避免严重的正常组织并发症。
