Characterization of the Radiation-Damaged Precursor Cells in Bone Marrow Based on Modeling of the Peripheral Blood Granulocytes Response

Hu, Shaowen; Cucinotta, Francis A.

doi:10.1097/hp.0b013e31820dba65

Cited by 24 publications

(10 citation statements)

References 27 publications

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“…The organs of the blood and hematopoietic systems are vulnerable to radiation [10] – [14] . Indeed, many studies have shown that radiation can cause a decrease in the visible components of blood [15] , cell morphology changes, alterations to the electrolyte state in peripheral blood (PB), mild hyperplasia in the bone marrow (BM) [16] , serious inhibition or even destruction of the bone marrow [17] , [18] , a reduction in the production of erythrocytes [19] , changes in the aggregation state of platelets [20] , and induction of the transformation of normal stem cells into tumor stem cells [20] – [22] . Thus, a hemogram of the blood system is often used initially as an approximate guide to assess the adverse effects caused by radiotherapy to the human body.…”

Section: Introductionmentioning

confidence: 99%

Erythrocyte Stiffness during Morphological Remodeling Induced by Carbon Ion Radiation

et al. 2014

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The adverse effect induced by carbon ion radiation (CIR) is still an unavoidable hazard to the treatment object. Thus, evaluation of its adverse effects on the body is a critical problem with respect to radiation therapy. We aimed to investigate the change between the configuration and mechanical properties of erythrocytes induced by radiation and found differences in both the configuration and the mechanical properties with involving in morphological remodeling process. Syrian hamsters were subjected to whole-body irradiation with carbon ion beams (1, 2, 4, and 6 Gy) or X-rays (2, 4, 6, and 12 Gy) for 3, 14 and 28 days. Erythrocytes in peripheral blood and bone marrow were collected for cytomorphological analysis. The mechanical properties of the erythrocytes were determined using atomic force microscopy, and the expression of the cytoskeletal protein spectrin-α1 was analyzed via western blotting. The results showed that dynamic changes were evident in erythrocytes exposed to different doses of carbon ion beams compared with X-rays and the control (0 Gy). The magnitude of impairment of the cell number and cellular morphology manifested the subtle variation according to the irradiation dose. In particular, the differences in the size, shape and mechanical properties of the erythrocytes were well exhibited. Furthermore, immunoblot data showed that the expression of the cytoskeletal protein spectrin-α1 was changed after irradiation, and there was a common pattern among its substantive characteristics in the irradiated group. Based on these findings, the present study concluded that CIR could induce a change in mechanical properties during morphological remodeling of erythrocytes. According to the unique characteristics of the biomechanical categories, we deduce that changes in cytomorphology and mechanical properties can be measured to evaluate the adverse effects generated by tumor radiotherapy. Additionally, for the first time, the current study provides a new strategy for enhancing the assessment of the curative effects and safety of clinical radiotherapy, as well as reducing adverse effects.

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Section: Introductionmentioning

confidence: 99%

Erythrocyte Stiffness during Morphological Remodeling Induced by Carbon Ion Radiation

et al. 2014

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“…Change in the cellular concentration in blood is one of the most important biomarkers to assess the extent of injury caused by acute radiation exposure (Hu & Cucinottam, ). Figures and show the responses of different blood cell types (lymphocytes, granulocytes, leukocytes, and platelets) to the Orion MPCV storm shelter radiation environment during the 5 × October 1989 SEP event (note that the storm shelter BFO dose rates are multiplied by a factor of 5), for male and female body types, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The organ dose estimate is based on a fitting procedure between the real‐time vehicle dosimeter measurements and a precomputed database of dose quantities calculated from the HZETRN radiation transport code (Slaba et al, ; Wilson et al, ), including the actual MPCV vehicle geometry and mass distribution. The estimated organ doses at the crew locations provide the necessary inputs to biological response models that predict clinically important syndromes associated with ARS and quantify radiation‐induced performance decrement (Hu & Cucinottam, ; Hu et al, , ). The active dosimeter‐based SEP organ dose estimate methodology presented in this paper will be tested operationally on NASA's Exploration Mission 1 (EM‐1) and fully utilized on NASA's EM‐2 (searched on 27 March 2018, https://www.nasaspaceflight.com/2012/06/nasa-teams-evaluating-iss-built-exploration-platform-roadmap/ and https://www.nasaspaceflight.com/2017/09/sls-em-1-em-3-notional-mission-outline/).…”

Section: Introductionmentioning

confidence: 99%

Active Dosimeter‐Based Estimate of Astronaut Acute Radiation Risk for Real‐Time Solar Energetic Particle Events

Mertens

Slaba

2018

Space Weather

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Radiation exposure from solar energetic particle (SEP) events becomes a much greater concern as human exploration extends beyond low Earth orbit and the protective environment of Earth's magnetic field. Free‐space SEP events have an increased impact on mission planning and operations, as countermeasures may be necessary to avoid exceeding astronaut permissible exposure limits. Operational analysis tools are needed to assess acute radiation risk during SEP events in order to determine courses of action during the mission. A methodology has been developed to meet this need, which utilizes onboard vehicle dosimeter measurements to estimate organ dosimetric quantities at astronaut crew locations in real time. The estimated organ doses provide the necessary inputs to acute biological response models that predict radiation‐induced performance decrement and other acute radiation effects. The real‐time SEP organ dose estimation methodology has been combined with an acute biological response model, providing an active dosimeter‐based acute radiation risk model for operational mission planning, and determining radiation exposure mitigation measures for deep‐space exploration missions. This new tool has been developed specifically for National Aeronautics and Space Administration's Orion Multi‐Purpose Crew Vehicle storm shelter environment but could easily be extended to other vehicles. The methodology for estimating SEP organ doses is evaluated and assessed in this paper, and a simulation of the acute radiation responses in the Multi‐Purpose Crew Vehicle storm shelter is shown for the historical October 1989 SEP event. The operational acute radiation risk model will be utilized on National Aeronautics and Space Administration's Exploration Mission 1 and Exploration Mission 2.

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“…[12] In a study by Hu, after 3.3 Gy, 60 days were required for neutrophils to return to 95% of their normal values and for lymphocytes to return to 55% of their normal levels. [21] Also, Inoue et al showed radioresistant stem cell subfraction nine days after exposure to 4-6 Gy in mice. [22] Similarly, we found that 7 and 14 days after 5 Gy TBI, almost 20% of leucocytes and lymphocytes were radioresistant, possibly by means of radioresistant stem cells.…”

Section: Tablementioning

confidence: 99%

Flow Cytometric Analysis of Depletion and Recovery Kinetics of T Cell Subsets in Rats After Total-Body- Irradiation: Footprints of Treg-Augmented Immunosuppression

Kıraklı¹

2018

TJ Oncol

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Total-body-irradiation (TBI) causes significant immunosuppression, but different lymphocyte subsets have various radiosensitivities. Regulatory T (Treg) cells, which are crucial for self-tolerance and are potent suppressors of antitumor immunity are found to be resistant to radiotherapy (RT) compared with T helper (Th) cells and Cytotoxic-T lymphocytes (CTL) in both in-vivo and in-vitro studies, but the data on this subject is relatively scarce. Besides, recent developments in the context of combination of immunotherapy with RT compelled us to revisit the concept of radiation-induced quantitative and functional changes in lymphocyte subsets by flow cytometry using animal models with the aim of transitioning the findings to clinical studies. METHODS Twenty-three Swiss albino rats were exposed to TBI at a single fraction of 5 Gy. Immediately prior to irradiation, at time points of 1 day and 7 and 14 days post-TBI, flow cytometric analyses were performed. RESULTS There has been statistically significant decrease in all T lymphocyte subsets at 1, 7 and 14 days post-TBI. The decrease in Th subset was more pronounced compared to CTL. Baseline CD4+/CD8+ ratio was 0.85 which significantly decreased to 0.29 1 day post-TBI, then increased steadily in subsequent measurements and reached near normal. The number of Treg cells markedly declined to 6.5% of baseline value one day after TBI, and then steadily increased during the follow-up. By the end of 14 days, it reached half of its baseline value. CONCLUSION Radiation-induced immunosuppression may be explained not only by the decrease in lymphocyte cell number but also by the relative increase in Treg cell number because the higher regenerative capacity may present an additional role.

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Characterization of the Radiation-Damaged Precursor Cells in Bone Marrow Based on Modeling of the Peripheral Blood Granulocytes Response

Cited by 24 publications

References 27 publications

Erythrocyte Stiffness during Morphological Remodeling Induced by Carbon Ion Radiation

Erythrocyte Stiffness during Morphological Remodeling Induced by Carbon Ion Radiation

Active Dosimeter‐Based Estimate of Astronaut Acute Radiation Risk for Real‐Time Solar Energetic Particle Events

Flow Cytometric Analysis of Depletion and Recovery Kinetics of T Cell Subsets in Rats After Total-Body- Irradiation: Footprints of Treg-Augmented Immunosuppression

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