Chronic radiation leukemogenesis: postnatal hematopathologic effects resulting from in-utero irradiation

Previous studies have shown that continuous whole-body exposure to low daily doses of gamma radiation is highly leukemogenic for beagles initially exposed during either young adulthood or fetal development. In contrast, terminated radiation-exposure regimens (continuous exposure terminated after accumulation of preset total radiation doses) markedly reduce leukemogenic potential. In this study, we examined leukemic incidences and postnatal hematopoietic function in three groups of dogs; continuously irradiated (7.5 cGy/day) during both fetal life and after birth, continuously irradiated during fetal life only, and nonirradiated. Results were compared to results from studies with similarly irradiated and nonirradiated groups of young adult dogs initially tested at 400 days of age. Hematopoietic function was assessed in terms of both circulating blood levels of red cells, platelets, granulocytes, and monocytes, and marrow concentrations and radiosensitivities of hematopoietic progenitors. Results indicated that under continuous fetal/postnatal irradiation, i.e. the high leukemogenic exposure regimen, a marked, progressive suppression in hematopoietic function occurred following birth. This suppression continued to 100-150 days of age and was followed by partial hematopoietic recovery that was associated with an acquired radioresistance by hematopoietic progenitors. In contrast, neonates that had been continuously irradiated during fetal life, but not postnatally, i.e. the low leukemogenic regimen, exhibited a similar initial suppression of hematopoietic function followed by partial recovery. However, no temporally linked acquisition of radioresistance by hematopoietic progenitors was demonstrated. These results support the hypothesis, developed from earlier studies with adult dogs, that the processes of acquired radioresistance and recovery in numbers of transformable hematopoietic progenitors are causally linked to early stages of the leukemogenic process under continuous ionizing irradiation.