Fractionation effects and repair kinetics in rat kidney

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.