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LATE EFFECTS OF CONTINUOUS IRRADIATION: THE RELATION OF HEMATOLOGICAL INJURY TO LETHALITY

Journal Article · · Laval Medical (Canada)
OSTI ID:4715360
Experiments are reported in which 5000 mice, both sexes of a first generation hybrid, were irradiated with 22 treatment levels ranging from 5 to 2500 r/day. Treatment began at 100 days of age and continued daily for the remainder of life. The relation of mean after-survival time to accumulated dose shows that the mean accumulated dose (MAD) is high at the shortest survival times. It decreases to a well defined minimum at 7 days, followed by a brief rise and more extended fall to a second minimum at about 18-20 days, followed by a rise to about 200 days that is interrupted by a shallow but significant minimum at about 40 days. Beyond 200 days natural aging takes over, and MAD decreases steadily, to reach zero at the control survival time. If the reciprocal of daily dose is plotted as ordinate against mean after-survival time on the abscissa, the curve increases to the right, but in a series of steps with the successive rises centered at about 5, 13, and 40 days. The curve is interpreted as describing the time-course of accumulation of potentially lethal injury in a population given a constant daily dose. The points of steepest rise are times of most rapid accumulation of injury. The pronounced peaks present at 5 and 13 days correspond respectively to the syndromes of intestinal and leukopoietic damage following a single radiation dose. The third peak at 40 days has no corresponding single- dose syndrome because the third process is less radiosensitive than the first 2 and hence rarely has a lethal outcome in animals that survive the first 2. It is conjectured that the 40-day process relates to disturbance of the circulating red cell level, and evidence in support of this is reported. The pattern of change in the hemoglobin levels of continuously irradiated mice shows a progressive decrease at the highest daily dosages, an arrest or slight rise at 22 days at lower levels, and almost complete compensation at the lowest levels. The decrease of red cell count with age was shared by control and irradiated groups, and the very considerable depression of red cell count occurred at dosage levels without depression of hemoglobin. This suggests that the circulating hemoglobin level has a stronger homeostatic control than does red cell level, or a lesser vulnerability to age and radiation damage, or both. The absolute reticulocyte counts show a rebound at about 20 days, and the increase over controls beyond 100 days is striking. The tendency of almost all elements (lymphocytes, platelets, neutrophils, etc.) to rebound at 22 days requires explanation in terms of systemic physiology rather than of intracellular processes. It is proposed that a phenomenon of radiation lethality observed in the 20--40-day period after beginning of exposure is due to the action of sex hormones and somatotropic hormone. It is also postulated that the blood element most gravely injured at a given tl me is the most important contributor to lethality at that time. Of the elements studied, only the granulocyte level has any strong involvement at 11 days. The hematocrit showed maximum gravity of injury at 47 days, which is close to the maximum at 40 days in the lethality process. Lymphocytes show no peaks of gravity of injury, but the progressive depression may lead to diseases arising from lymphopenia late in life. (TCO)
Research Organization:
Argonne National Lab., Ill.
NSA Number:
NSA-17-027148
OSTI ID:
4715360
Report Number(s):
TID-17645; 0023-9046
Journal Information:
Laval Medical (Canada), Journal Name: Laval Medical (Canada) Vol. Vol: 34; ISSN LAMEA
Country of Publication:
Country unknown/Code not available
Language:
English