Wong C S, Hao Y
Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Ontario, Canada.
Int J Radiat Oncol Biol Phys. 1997 Jan 1;37(1):171-9. doi: 10.1016/s0360-3016(96)00453-1.
This study aimed to assess the influence of the level of initial injury on the long-term recovery kinetics of radiation damage in the central nervous system using a rat spinal cord model.
The adult rat spinal cord (C2-T2) was initially given two or three daily fractions of 9 Gy, or three daily fractions of 10.25 Gy. At day 4 or weeks 6, 8, 12, 20, 28, 40, or 52, animals were reirradiated with graded single doses of X rays. The end point was forelimb paralysis caused by white-matter necrosis.
Latent times to paralysis as measured from the date of the initial treatment increased with increasing time interval between initial treatment and reirradiation but decreased with increasing size of initial injury. Retreatment ED50s were 14.1, 14.8, 15.4, 16.3, and 16.2 Gy for animals reirradiated at day 4 and weeks 8, 12, 20, and 28, respectively, after an initial dose of 9 Gy x 2. After 9 Gy x 3, the retreatment ED50s at day 4 and weeks 6, 8, 12, 20, 28, 40, and 52 were 10.0, 9.9, 9.8, 12.0, 13.9, 14.6, 14.7, and 15.5 Gy, respectively. For an initial dose of 10.25 Gy x 3, the retreatment ED50s at day 4 and weeks 8, 12, 20, 28, and 40 were 5.8, 6.1, 8.4, 10.6, 12.2, and 13.3 Gy, respectively. Using the linear-quadratic (LQ) model, alpha/beta of 3.0 Gy, to quantitate the biological effect of the different retreatment schedules, the initial doses of 9 Gy x 2 or 3, or 10.25 Gy x 3 were found to represent 47, 71, and 89% of the extrapolated response dose (ERD), respectively, and no significant increase in tolerance was observed for retreatment given within 8 weeks of initial treatment. Significant long-term recovery was observed thereafter and increased with increasing time interval to retreatment. The retreatment tolerance and radiation damage recovered at different intervals were influenced by the initial dose. Using direct analysis, the recovery kinetics could be best described by introducing a time function consisting of a linear and quadratic time component dependent on initial dose to the LQ model.
These results are consistent with the presence of significant long-term recovery of radiation damage in rat spinal cord, and suggest that the size of the initial damage influences the recovery kinetics, and hence the retreatment tolerance.
本研究旨在利用大鼠脊髓模型评估初始损伤程度对中枢神经系统辐射损伤长期恢复动力学的影响。
成年大鼠脊髓（C2-T2）最初接受每日两次或三次9 Gy照射，或每日三次10.25 Gy照射。在第4天或第6、8、12、20、28、40或52周时，对动物进行分级单次X射线再照射。终点指标为白质坏死导致的前肢麻痹。
从初始治疗日期开始测量的麻痹潜伏期随着初始治疗与再照射之间时间间隔的增加而延长，但随着初始损伤程度的增加而缩短。对于初始剂量为9 Gy×2后在第4天和第8、12、20和28周再照射的动物，再治疗的半数有效剂量（ED50）分别为14.1、14.8、15.4、16.3和16.2 Gy。在9 Gy×3照射后，第4天和第6、8、12、20、28、40和52周的再治疗ED50分别为10.0、9.9、9.8、12.0、13.9、14.6、14.7和15.5 Gy。对于初始剂量为10.25 Gy×3，第4天和第8、12、20、28和40周的再治疗ED50分别为5.8、6.1、8.4、10.6、12.2和13.3 Gy。使用线性二次（LQ）模型，α/β为3.0 Gy，以量化不同再治疗方案的生物学效应，发现9 Gy×2或3或10.25 Gy×3的初始剂量分别代表外推反应剂量（ERD）的47%、71%和89%，并且在初始治疗后8周内进行再治疗时未观察到耐受性显著增加。此后观察到显著的长期恢复，并且随着再治疗时间间隔的增加而增加。不同时间间隔恢复的再治疗耐受性和辐射损伤受初始剂量影响。通过直接分析，通过在LQ模型中引入一个由依赖于初始剂量的线性和二次时间成分组成的时间函数，可以最好地描述恢复动力学。
这些结果与大鼠脊髓辐射损伤存在显著的长期恢复一致，并表明初始损伤的大小影响恢复动力学，进而影响再治疗耐受性。
