Effects of High- and Low-LET Radiation on Human Hematopoietic System Reconstituted in Immunodeficient Mice

Abstract

Over the last 50 years, a number of important physiological changes in humans who have traveled on spaceflights have been catalogued. Of major concern are the short-and long-term radiationinduced injuries to the hematopoietic system that may be induced by high-energy galactic cosmic rays encountered on interplanetary space missions. To collect data on the effects of space radiation on the human hematopoietic system in vivo, we used a humanized mouse model. In this study, we irradiated humanized mice with 0.4 Gy of 350 MeV/n 28 Si ions, a dose that has been shown to induce tumors in tumor-prone mice and a reference dose that has a relative biological effectiveness of 1 (1 Gy of 250-kVp X rays). Cell counts, cell subset frequency and cytogenetic data were collected from bone marrow spleen and blood of irradiated and control mice at short-term (7, 30 and 60 days) and long-term (6-7 months) time points postirradiation. The data show a significant short-term effect on the human hematopoietic stem cell counts imparted by both high-and low-LET radiation exposure. The radiation effects on bone marrow, spleen and blood human cell counts and human cell subset frequency were complex but did not alter the functions of the hematopoietic system. The long-term data acquired from high-LET irradiated mice showed complete recovery of the human hematopoietic system in all hematopoietic compartments. The combined results demonstrate that, in spite of early perturbation, the longer term effects of high-LET radiation are not detrimental to human hematopoiesis in our system of study.

Effects of exposure to low-dose ionizing radiation on changing platelets: a prospective cohort study

“…The hematopoietic system of the human body that is sensitive to ionizing radiation has been evaluated in many studies [ 10 , 20 , 21 ]. According to reports, ionizing radiation exposure causes biological effects on human health including hematological parameters that change sooner or later, and hematopoietic syndrome is observed in animals and humans after systemic radiation exposure [ 22 ], including myelodysplastic disease by platelet elevation causing and chronic myelogenous leukemia [ 23 – 25 ].…”

“…The findings provide a reasonably consistent picture of changing into hematological parameters associated with exposure to radiation. Moreover, there is a supplement to the risk assessment of low-dose ionizing radiation based on animal models [ 20 , 27 , 28 ].…”

“…Significant associations with radiation for the hematological parameters were reported on medical occupational workers at a large hospital with a lower mean of the total white blood cell and the neutrophils than the control group [ 34 ], while these studies may have limitations on sample selection risk factors of changing into hematological parameter levels and personal dose monitoring. The low-dose mouse model experiment also found ionizing radiation damaged to the hematopoietic system including granulocytes in the irradiated mice increased by 1.7 times of the seventh day of the experiment [ 20 ]. Another study also found this effect of cumulative dose, long-term ionizing radiation inhibits blood cell production, and only a few past years of exposure contribute to the observed hematological parameter declines to include platelets [ 14 , 35 ].…”

Effects of Low Dose Space Radiation Exposures on the Splenic Metabolome

“…Although secondary immune organs are impacted by radiation, it remains to be investigated if there is a persistent shift in cell populations within this tissue at a longer time point after the exposure and how this could impact the adaptive response. Some studies have shown that both B-cells and T-cells are impacted by radiation in the spleen [ 25 , 60 ], including in humanized mice [ 61 ]. However, long-term responses to 28 Si irradiations did not reveal any differences in the population of humanized cells, compared to controls [ 61 ], or significant changes in the B- and T-cell populations in the spleen of mice [ 60 ] with 56 Fe.…”

“…Some studies have shown that both B-cells and T-cells are impacted by radiation in the spleen [ 25 , 60 ], including in humanized mice [ 61 ]. However, long-term responses to 28 Si irradiations did not reveal any differences in the population of humanized cells, compared to controls [ 61 ], or significant changes in the B- and T-cell populations in the spleen of mice [ 60 ] with 56 Fe. However, Gridley et al did conclude that the more complex space radiation environment may lead to a broader immune dysfunction [ 60 ].…”