Recuperation from Lethal Injury by Whole-Body Irradiation: I. Kinetic Aspects and the Relationship with Conditioning Dose in C57BL Mice

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Abstract
Mature male C57BL mice were whole body irradiated, either with single 250-KV X-ray doses of short duration or with graded series of second doses at different times after 1 of 3 constant conditioning doses (Dc). Second doses were administered at 2-hour intervals during the first 12 hours and at 6- to 12-hour intervals thereafter up to 48 hours. The LD50''s were determined for the 30 days post-irradiation, and these data were used for the calculation of residual injury and recovery, or roentgens repaired. The % residual injury remaining after all 3 Dc''s showed characteristic fluctuations, with a minimum (period of marked second-dose refractoriness) falling at 4 to 9 hours and a maximum at 8 to 10 hours. These fluctuations are a cyclic phenomenon in the period between approximately 12 and 48 hours, as evidenced by additional experiments in which mortality was determined after constant second doses given at 2- to 3-hour in-tervals for the entire 48 hours after a Dc of 154 r. The magnitudes of the initial minima and maxima in % residual injury were independent of the size of the Dc. The decay in % residual injury in the 12- to 48-hour period was an exponential function with superimposed cyclic fluctuations. The rate of decay was strongly first-dose-dependent, proceeding more slowly, the higher the Dc. The same data, however, analyzed for recovery, in absolute number of roentgens repaired per hour, did not differ significantly for the 3 Dc''s during this same period, and an arithmetically linear relation between roentgens repaired and time was adequately fitted to the experimental points. The observed LD5o''s are related to the probabilities of survival of individual marrow stem cells, and the changes in LD50 to the combined effects of cellular depopulation and synchronization in the postirradiation growth of first-dose surviving cells. At the time of conditioning irradiation the cell population is assumed to be heterogeneous with respect to the stages of the generation cycle and therefore with respect to stage-dependent radiosensitivity. The first dose effectively synchronizes the surviving cells so that their net radiosensitivity assumes different levels at different times.