Survival Patterns and Hemopathological Responses of Dogs Under Continuous Gamma Irradiation

Abstract

Survival curves were constructed and analyzed relative to contributing hematopathological responses for groups of beagles exposed continuously for duration of life to low daily doses of whole body 60Co gamma irradiation (27.3 rads/day to 4 rads/day). The survival curves versus time were progressively displaced toward longer survival as rates of exposure were reduced from the relatively high dose rate of 27.3 rads/day to the low dose rate of 4.0 rads/day. Average survival times increased from 57 days at 27.3 rads/day to 1830 days at 4.0 rads/day, representing fractional increased life-spans from 1.5% to 50.8%, respectively. Survival curves versus total dose were markedly displaced along the cumulative radiation dose axis at the extreme dose rates (i.e., 27.3 and 4.0 rads/day), but not at the intermediate dose rates (i.e., 13.4 and 7.9 rads/day) in which the upper linear portions of the survival curves are superimposed. From these dose-dependent survival curves, LD 50 values for whole body gamma irradiation, delivered chronically at 27.3, 13.4, 7.9, and 4.0 rads per day were estimated to be 1442, 2124, 2039, and 7161 rads, respectively. Both time- and dose-dependent survival curves for the intermediate dose rates, in contrast to the extreme dose rates, exhibited pronounced transitions in the lethality rate below the 50% survival level. These lethality rate transitions occurred at ~ 2500 rads of accumulated dose and were attributed to a shift in the spectrum of developing hematopathologies: namely, from a predominance of the acutely ablative radiation-induced lymphohematopoietic syndromes (i.e., septicemias and aplastic anemias) to a predominance of the late arising hematopoietic neoplasias (myelogenous leukemia and related myeloproliferative disorders). Based on the concept that these lethality rate transitions and shifts in the spectrum of developing pathologies reflect distinct subgroups of dogs of varying radiosensitivities and pathological tendencies, estimates of LD values for subgroups with specific pathologies are given (e.g., 1850 rads for the subgroup with aplasia; 5500 rads for the subgroup with myeloproliferative diseases). Sequential analyses of blood and marrow responses indicated that this shift in hematopathologic spectrum (and in turn the lethality rate transition) is due to an early reparative hematological event that is prerequisite to prolonged survival and, in turn, to the expression of late arising neoplasias. The cellular basis of this repair appears to be mediated, in part, by an acquisition of radioresistance by early hematopoietic progenitors.