Effects of heavy ions on cycling stem cells

Hagan, Michael P.; Holahan, Eugene V.; Ainsworth, E. J.

doi:10.1016/0273-1177(86)90293-0

Cited by 5 publications

(4 citation statements)

References 19 publications

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“…We previously reported that a f »: single hind leg irradiation, the CFU-S content was decreased in both femurs, and the fraction of cells in DNA synthesis was increased late in life in both the irradiated and non-irradiated femur;*2. *3 trms t he regulatory process is not only local (33).…”

Section: Discussionmentioning

confidence: 99%

“…Because of the low fluence, damage interactions between high-and low-LET radiation events are not expected to be of significance. The dose or number of particles necessary to trigger cells into proliferation should be determined (33,56). Alterations in the proliferative status of tissues produced by radiation, stress, microgravity, or a combination of these factors could influence susceptibility to subsequent irradiation or to expression of neoplastic or non-neoplastic damage.…”

Section: Discussionmentioning

confidence: 99%

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Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

Ainsworth

Afzal

Crouse

et al. 1989

Advances in Space Research

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Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for gamma-radiation. When total doses of 96 or 247 cGy of neutrons or gamma rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and gamma-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or gamma rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for gamma rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

Ainsworth

Afzal

Crouse

et al. 1989

Advances in Space Research

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“…1,[4][5][6] High atomic number and energy (HZE) particles such as carbon, oxygen, silicon, and iron are important component sof space radiation, from the solar particle events and the galactic cosmic rays. 7,8 Compared to photon and proton radiation, HZE particles bearing higher energy could cause both acute and long-term damage to bone marrow via increased production of reactive oxygen species, showing stronger detrimental effects (with higher relative biological effectiveness) on the hematopoietic system including decreased peripheral blood counts and reduced hematopoietic stem cells (HSCs) and progenitor cells (HPCs) in laboratory animal models [9][10][11][12][13][14][15][16][17][18][19][20] and, in addition, raising hematological cancer risk via bone marrow cell reprograming. 21 The AR mouse model for rescuing bone marrow death established by Yonezawa and colleagues 1,[22][23][24] was repeatedly verified.…”

Section: Introductionmentioning

confidence: 99%

Increased Hematopoietic Stem Cells/Hematopoietic Progenitor Cells Measured as Endogenous Spleen Colonies in Radiation-Induced Adaptive Response in Mice (Yonezawa Effect)

et al. 2018

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The existence of radiation-induced adaptive response (AR) was reported in varied biosystems. In mice, the first in vivo AR model was established using X-rays as both the priming and the challenge doses and rescue of bone marrow death as the end point. The underlying mechanism was due to the priming radiation-induced resistance in the blood-forming tissues. In a series of investigations, we further demonstrated the existence of AR using different types of ionizing radiation (IR) including low linear energy transfer (LET) X-rays and high LET heavy ion. In this article, we validated hematopoietic stem cells/hematopoietic progenitor cells (HSCs/HPCs) measured as endogenous colony-forming units-spleen (CFU-S) under AR inducible and uninducible conditions using combination of different types of IR. We confirmed the consistency of increased CFU-S number change with the AR inducible condition. These findings suggest that AR in mice induced by different types of IR would share at least in part a common underlying mechanism, the priming IR-induced resistance in the blood-forming tissues, which would lead to a protective effect on the HSCs/HPCs and play an important role in rescuing the animals from bone marrow death. These findings provide a new insight into the mechanistic study on AR in vivo.

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“…A plethora of studies including ours have reported that photon radiation (such as γ-rays) induced both acute and chronic bone marrow (BM) suppression, especially the long-term defect of hematopoietic stem cells (HSCs), resulting from radiation-induced production of reactive oxygen species (ROS), DNA damage, apoptosis, and cellular senescence[ 7 – 9 ]. Previous studies have demonstrated that exposure of mice to high energy 56 Fe, 12 C and neutron had detrimental effects on the hematopoietic system, including decreased peripheral blood counts and reduced colony forming ability of HSCs and hematopoietic progenitor cells (HPCs) [ 2 , 10 – 12 ]. However, the hematopoietic effects of high energy 16 O irradiation have been barely studied.…”

Section: Introductionmentioning

confidence: 99%

Low doses of oxygen ion irradiation cause long-term damage to bone marrow hematopoietic progenitor and stem cells in mice

Wang

Chang

et al. 2017

PLoS ONE

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During deep space missions, astronauts will be exposed to low doses of charged particle irradiation. The long-term health effects of these exposures are largely unknown. We previously showed that low doses of oxygen ion (16O) irradiation induced acute damage to the hematopoietic system, including hematopoietic progenitor and stem cells in a mouse model. However, the chronic effects of low dose 16O irradiation remain undefined. In the current study, we investigated the long-term effects of low dose 16O irradiation on the mouse hematopoietic system. Male C57BL/6J mice were exposed to 0.05 Gy, 0.1 Gy, 0.25 Gy and 1.0 Gy whole body 16O (600 MeV/n) irradiation. The effects of 16O irradiation on bone marrow (BM) hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) were examined three months after the exposure. The results showed that the frequencies and numbers of BM HPCs and HSCs were significantly reduced in 0.1 Gy, 0.25 Gy and 1.0 Gy irradiated mice compared to 0.05 Gy irradiated and non-irradiated mice. Exposure of mice to low dose 16O irradiation also significantly reduced the clongenic function of BM HPCs determined by the colony-forming unit assay. The functional defect of irradiated HSCs was detected by cobblestone area-forming cell assay after exposure of mice to 0.1 Gy, 0.25 Gy and 1.0 Gy of 16O irradiation, while it was not seen at three months after 0.5 Gy and 1.0 Gy of γ-ray irradiation. These adverse effects of 16O irradiation on HSCs coincided with an increased intracellular production of reactive oxygen species (ROS). However, there were comparable levels of cellular apoptosis and DNA damage between irradiated and non-irradiated HPCs and HSCs. These data suggest that exposure to low doses of 16O irradiation induces long-term hematopoietic injury, primarily via increased ROS production in HSCs.

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Effects of heavy ions on cycling stem cells

Cited by 5 publications

References 19 publications

Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

Increased Hematopoietic Stem Cells/Hematopoietic Progenitor Cells Measured as Endogenous Spleen Colonies in Radiation-Induced Adaptive Response in Mice (Yonezawa Effect)

Low doses of oxygen ion irradiation cause long-term damage to bone marrow hematopoietic progenitor and stem cells in mice

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