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Effects of low level radiation upon the hematopoietic stem cell: Implications for leukemogenesis
Authors:E P Cronkite  V P Bond  A L Carsten  T Inoue  M E Miller  J E Bullis
Institution:(1) Medical Department, Brookhaven National Laboratory, 11973 Upton, NY, USA;(2) Department of Pathology, Yokohama City University Medical School, Yokohama;(3) Present address: Division of Hematologic Research, The Memorial Hospital, 02860 Pawtucket, RI, USA
Abstract:Summary These studies have addressed firstly the effect of single small doses of x-rays upon murine hematopoietic stem cells to obtain a better estimate of theD q . It is small, of the order of 20 rad.Secondly, a dose fractionation schedule that does not kill or perturb the kinetics of hemopoietic cell proliferation was sought in order to investigate the leukemogenic potential of low level radiation upon an unperturbed hemopoietic system. Doses used by others in past radiation leukemogenesis studies clearly perturb hemopoiesis and kill a detectable fraction of stem cells. The studies reported herein show that 1.25 rad every day decrease the CFU-S content of bone marrow by the time 80 rads are accumulated. Higher daily doses as used in published studies on radiation leukemogenesis produce greater effects.Studies on the effect of 0.5, 1.0, 2.0, and 3.0 rad 3 times per week are under way. Two rad 3 times per week produced a modest decrease in CFU-S content of bone marrow after an accumulation of 68 rad. With 3.0 rad 3 times per week an accumulation of 102 rad produced a significant decrease in CFU-S content of bone marrow. Dose fractionation at 0.5 and 1.0 rad 3 times per week has not produced a CFU-S depression after accumulation of 17 and 34 rad.Radiation leukemogenesis studies published to date have utilized single doses and chronic exposure schedules that probably have significantly perturbed the kinetics of hematopoietic stem cells. Whether radiation will produce leukemia in animal models with dose schedules that do not perturb kinetics of hematopoietic stem cells remains to be seen.Dedicated to Prof. L.E. Feinendegen on the occasion of his 60th birthdayResearch supported by the U.S. Department of Energy under contract DE-ACO2-7 6CH00016. Accordingly, the U.S. government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. government purpose
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