van Rongen E, Kuijpers W C, Madhuizen H T
Radiobiological Institute TNO, Rijswijk, The Netherlands.
Int J Radiat Oncol Biol Phys. 1990 May;18(5):1093-106. doi: 10.1016/0360-3016(90)90445-p.
Rat kidneys were unilaterally irradiated with up to 40 fractions of X rays. Fractionation regimens were given either with long intervals of 6-24 hr between fractions, resulting in complete recovery from sublethal damage, or with 1-hr intervals, resulting in largely incomplete repair. The non-irradiated kidney was surgically removed 4 weeks after the last fraction. The development of radiation-induced kidney damage was monitored by regular assessment of three different parameters indicative of kidney function: serum urea, the total volume of urine excreted in 24 hr and urine osmolality. At the end of the observation period, 18 months after treatment, the kidney was removed. The hydroxyproline content was determined and a histopathological analysis was performed. Since the 20 and 40-fraction data indicated a higher effectiveness of these regimens than would be expected on the basis of the LQ model, the data were divided in two subsets, 2-10 fractions (high doses per fraction) and 10-40 fractions (low doses per fraction), and analyzed separately. The time course of alpha/beta and T1/2 values was determined for each functional parameter separately, and for the data from the three parameters combined. A complex pattern was found, with the values for alpha/beta as well as T1/2 differing between the two data subsets between about 20 and 40 weeks after treatment. For the lower doses per fraction the alpha/beta values were generally higher and the repair half-times longer. After 40 weeks no significant differences were observed between the two data subsets. If the differences found earlier are ignored, overall alpha/beta and T1/2 values can be calculated. For early endpoints the alpha/beta was 1.69 (1.45, 1.90) Gy (95% confidence limits in parentheses), for late endpoints it was 1.77 (1.56, 2.00) Gy. The corresponding T1/2 values were 1.57 (1.44, 1.73) hr for early endpoints, and 2.10 (1.90, 2.34) hr for late endpoints. Hence, the alpha/beta values do not alter in time, but the T1/2 value for late damage might be higher than that for early damage.
对大鼠肾脏进行单侧X射线照射，照射剂量高达40次分割。分割方案分为两种，一种是每次分割间隔6至24小时的长间隔方案，可使亚致死性损伤完全恢复；另一种是每次分割间隔1小时的方案，导致大部分修复不完全。在最后一次分割后4周，通过手术切除未照射的肾脏。通过定期评估三个指示肾功能的不同参数来监测辐射诱导的肾损伤的发展：血清尿素、24小时内排出的尿液总体积和尿渗透压。在观察期结束时，即治疗后18个月，切除肾脏。测定羟脯氨酸含量并进行组织病理学分析。由于20次和40次分割的数据表明这些方案的有效性高于基于LQ模型预期的有效性，因此将数据分为两个子集，2至10次分割（每次分割高剂量）和10至40次分割（每次分割低剂量），并分别进行分析。分别为每个功能参数以及综合三个参数的数据确定α/β和T1/2值的时间进程。发现了一种复杂的模式，在治疗后约20至40周之间，两个数据子集之间的α/β值以及T1/2值有所不同。对于每次分割较低剂量，α/β值通常较高，修复半衰期较长。40周后，两个数据子集之间未观察到显著差异。如果忽略早期发现的差异，则可以计算总体α/β和T1/2值。对于早期终点，α/β为1.69（1.45，1.90）Gy（括号内为95%置信限），对于晚期终点，为1.77（1.56，2.00）Gy。相应的早期终点T1/2值为1.57（1.44，1.73）小时，晚期终点为2.10（1.90，2.34）小时。因此，α/β值不会随时间变化，但晚期损伤的T1/2值可能高于早期损伤的T1/2值。
