Joiner M C, Rojas A, Johns H
CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middlesex, U.K.
Int J Radiat Biol. 1989 Jun;55(6):993-1005. doi: 10.1080/09553008914551021.
A sensitive experimental design and data analysis were used to test rigorously whether the repair capacity in the skin of the mouse foot changes during a course of repeated 240 kVp X-ray doses. Any such changes might reflect saturation or induction of repair enzymes resulting from progressive radiation damage, but most importantly this assumption of equal effect per dose fraction is central to all analyses of multiple-fraction radiation treatments, and remained to be demonstrated conclusively in skin. An X-ray dose of 2.5 Gy was given two, eight, 14 or 20 times with an interfraction interval of 8 h. Individual skin reactions for each mouse were analysed separately, giving 139 estimates of the effectiveness of 2.5 Gy (approximately 35 in each of the four fractionation schedules). Regression analysis of effect per fraction versus number of fractions showed that there was no significant trend, i.e. the damage per fraction was constant regardless of the number of fractions used. The mean damage per fraction was 3.75 +/- 0.15 per cent (95 per cent CL) of the full underlying damage equivalent to transient moist desquamation, and the slope of this plot was 0.0075 per cent +/- 0.022 per cent (95 per cent CL) per fraction. It was concluded that the assumption of equal effect per fraction was not invalidated in mouse skin. Shorter interfraction intervals would not allow full repair between fractions, and this could be misinterpreted as a progressive loss of repair capacity in this type of experiment. This was tested in skin by giving 2.5 Gy doses two, eight and 14 times with a 1-h interfraction interval. Effect per fraction increased with number of fractions, by an extra 37 per cent from two to eight fractions and by a further 14 per cent from eight to 14 fractions, giving the illusion of loss of repair as predicted. This confirms the need to check that where loss of repair capacity is suspected, this is not due artifactually to incomplete repair between fractions in slowly repairing systems.
采用灵敏的实验设计和数据分析方法，严格测试在重复给予240 kVp X射线剂量的过程中，小鼠足部皮肤的修复能力是否发生变化。任何此类变化可能反映了渐进性辐射损伤导致的修复酶饱和或诱导，但最重要的是，每剂量分割等效效应的这一假设是所有多分割放射治疗分析的核心，并且仍有待在皮肤中得到确凿证明。以8小时的分割间期给予2.5 Gy的X射线剂量，分别照射2次、8次、14次或20次。对每只小鼠的个体皮肤反应进行单独分析，得出了139个关于2.5 Gy有效性的估计值（四种分割方案中每种方案约35个）。每分割效应与分割次数的回归分析表明，不存在显著趋势，即无论使用的分割次数如何，每分割的损伤是恒定的。每分割的平均损伤为相当于短暂湿性脱屑的完全潜在损伤的3.75%±0.15%（95%置信区间），该图的斜率为每分割0.0075%±0.022%（95%置信区间）。得出的结论是，每分割等效效应的假设在小鼠皮肤中并非无效。较短的分割间期不允许各分割之间充分修复，在这类实验中这可能被误解为修复能力的逐渐丧失。通过以1小时的分割间期给予2.5 Gy剂量，分别照射2次、8次和14次，在皮肤中对此进行了测试。每分割效应随分割次数增加，从2次分割到8次分割增加了37%，从8次分割到14次分割又进一步增加了14%，正如所预测的那样产生了修复能力丧失的假象。这证实了有必要检查在怀疑存在修复能力丧失的情况下，这是否并非人为地由于缓慢修复系统中各分割之间的不完全修复所致。
