Tsang R W, Joiner M C, Rojas A, Johns H
CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom.
Radiat Res. 1991 Feb;125(2):163-72.
The kinetics of repopulation of clonogens in skin after fractionated X-ray exposures was studied in a series of experiments using a top-up design. The feet of mice were exposed to small X-ray doses (1.5 or 2 Gy), given two or three times a day on consecutive days with a minimum interfraction interval of 8 h. A single top-up dose of d(4)-Be neutrons was then given at various intervals after the last X-ray fraction, typically on Days 1,4,8, 15, and 19. The acute skin reaction produced was scored an analyzed by both a standard 23-day averaging and a 7-day averaging procedure. Either method gave similar results and led to the same conclusions. The amount of top-up dose needed to produce a fixed skin reaction was used as a measure of the net effect of the X-ray treatments. This net effect is a result of the initial reduction in skin clonogens due to X rays, and their repopulation before the top-up dose was given. Repopulation was not detected during any of these courses of fractionated treatment, up to an overall time of at least 12 and possibly 16 days. On completion of X-ray schedules lasting 6-16 days, repopulation started 4 days later. In contrast, this delay lengthened to approximately 8 days for shorter overall treatment times of 3-4 days. Once repopulation started, it proceeded rapidly over 11 days so that by 15 days after the cessation of X rays, the skin was restored almost to its normal state with respect to radiosensitivity. The residual damage from Day 15 to Day 19 postirradiation was 3-13% of a full-effect level. The rate of repopulation can be expressed as a clonogen doubling time (Tclon), assuming that an average skin reaction of 1.5 is equivalent to a clonogen surviving fraction of 1.7 x 10(-5). Tclon varied inversely with the amount of initial damage inflicted by the X rays, with the shortest values (1-1.3 days) seen following X-ray doses that gave an initial damage level of 60-80% of full effect. These data are consistent with a hypothesis that damage is "sensed" only 10-12 days after the first X-ray fraction, which provides the stimulus for repopulation of the target cells in the basal layer, the keratinoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
在一系列采用补充设计的实验中，研究了分次X射线照射后皮肤中克隆原细胞再增殖的动力学。给小鼠足部施加小剂量X射线（1.5或2 Gy），连续数天每天照射2或3次，最小分次间隔为8小时。在最后一次X射线分次照射后的不同时间间隔，通常在第1、4、8、15和19天，给予单次补充剂量的d(4)-Be中子。对产生的急性皮肤反应按标准的23天平均法和7天平均法进行评分和分析。两种方法得出的结果相似，结论相同。将产生固定皮肤反应所需的补充剂量用作X射线治疗净效应的指标。这种净效应是X射线导致皮肤克隆原细胞最初减少以及在给予补充剂量之前其再增殖的结果。在这些分次治疗过程中，直至至少12天甚至可能16天的总时间内，均未检测到再增殖现象。在持续6 - 16天的X射线照射方案结束后，再增殖在4天后开始。相比之下，对于3 - 4天的较短总治疗时间，这种延迟延长至约8天。一旦再增殖开始，它在11天内迅速进行，以至于在X射线照射停止后15天时，皮肤在放射敏感性方面几乎恢复到正常状态。照射后第15天至第19天的残余损伤为全效水平的3%至13%。假设平均皮肤反应为1.5相当于克隆原细胞存活分数为1.7×10⁻⁵，则再增殖速率可以表示为克隆原细胞倍增时间（Tclon）。Tclon与X射线造成的初始损伤量成反比，在初始损伤水平为全效的60% - 80%的X射线剂量后观察到最短值（1 - 1.3天）。这些数据与以下假设一致：损伤仅在第一次X射线分次照射后10 - 12天被“感知”，这为基底层中的靶细胞即角质形成细胞的再增殖提供了刺激。（摘要截选至250字）
