About THREE

The Health Risks of Extraterrestrial Environments (THREE), is an encyclopedic site whose goal is to present a discussion of the space radiation environment and its health risks to humans. The intent is to make this a good starting point for researchers new to either space, radiation, or both; a source of useful information for established investigators; and a teaching tool for students. Show More

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In The News - December 2022

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Current Research Citations

Female astronauts: Impact of space radiation on menopause

Bruce I. Rose, Eur J Obstet Gynecol Reprod Biol. 2022 Apr 1;271:210-3.

[04/01/2022]
Summary:

Space travel has different effects on the reproductive capacity of women compared to men. The radiation exposure intrinsic to deep space travel causes destruction of some of a woman's primordial follicles. Data suggests that a typical Mars mission may reduce a women's ovarian reserve by about 50%. This has consequences to a woman's reproductive capacity and, more significantly, decreases the time interval to her menopause. A reduced time interval to menopause is associated with earlier mortality. Estrogen replacement therapy and cryopreservation of a female astronaut's oocytes may be used to address these issues. However, cortical tissue freezing provides advantages to more directly compensate for these workplace complications. Cortical tissue freezing especially provides advantages if there are plans to reproduce in an extraterrestrial location.


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Impact of Radiation Quality on Microdosimetry and Chromosome Aberrations for High-Energy (>250 MeV/n) Ions.

Poignant, F.; Plante, I.; Crespo, L.; Slaba, T. Life 2022, 12, 358.

[03/09/2022]
Summary:

Using the models RITRACKS (track structure) and RITCARD (chromosome aberration), we studied how radiation quality impacts two endpoints: single-ion energy deposition spectra (microdosimetry in targets the size of a cell nucleus) and chromosome aberration yields. Calculations were performed for high-energy (> 250 MeV/n) mono-energetic ion beams with linear energy transfer (LET) varying from 0.22 to 149.9 keV/µm, and poly-energetic beams after the transport of the mono-energetic ion beams in a digital mouse model, representing the radiation exposure of a cell in a tissue. To discriminate events from ion tracks directly traversing the nucleus, to events from δ-electrons emitted by distant ion tracks, we categorized ion contributions to both endpoints into direct and indirect contributions, respectively. For microdosimetry, the indirect contribution is largely independent of the beam LET and minimally impacted by the beam interactions in mice. In contrast, the direct contribution is strongly dependent on the beam LET and shows increased probabilities of having low and high-energy deposition events when considering beam transport. Regarding chromosome aberrations, the indirect contribution induces a small number of simple exchanges, and a negligible number of complex exchanges. The direct contribution is responsible for most simple and complex exchanges. The complex exchanges are significantly increased for some low-LET ion beams when considering beam transport.


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Race and ethnic group dependent space radiation cancer risk predictions.

Cucinotta FA, Saganti PB. Sci Rep. 2022 Feb 7;12(1):2028  

[02/20/2022]
Summary:

Future space missions by national space agencies and private industry, including space tourism, will include a diverse makeup of crewmembers with extensive variability in age, sex, and race or ethnic groups. The relative risk (RR) model is used to transfer epidemiology data between populations to estimate radiation risks. We apply the NSCR-2020 model to make the first predictions of age dependent space radiation cancer risks for several U.S. populations, which includes Asian-Pacific Islanders (API), Black, Hispanic (white and black), and White (non-Hispanic) populations. Results suggest that male API and Hispanic populations have the overall lowest cancer risks, while White females have the highest risk. Blacks have similar total cancer rates than Whites, however their reduced life expectancy leads to modestly lower lifetime radiation risks compared to Whites. There are diverse tissue specific cancer risk ranking across sex and race, which include sex specific organ risks, female's having larger lung, stomach, and urinary-bladder radiation risks, and male's having larger colon and brain risks.


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The radiobiology of TGFβ

Mary Helen Barcellos-Hoff, Semin Cancer Biol. 2022 Feb 2;S1044-579X(22)00022-0. Online ahead of print. 

[02/16/2022]
Summary:

Although the therapeutic effect of radiation is attributed to induction of DNA damage that kills cancers cells, radiation also activates transforming growth factor β (TGFβ), a ubiquitously expressed cytokine that acts as biological lynchpin to promote malignancy, a permissive tumor microenvironment and immune evasion. The radiobiology of TGFβ unifies targets at the forefront of oncology—the DNA damage response and immunotherapy. This review covers the mechanisms by which radiation induces TGFβ activation, how TGFβ regulates DNA repair, and the dynamic regulation of the tumor immune microenvironment that together oppose effective cancer therapy.


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Quantification of radiation-induced DNA double strand break repair foci to evaluate and predict biological responses to ionizing radiation

Penninckx S, Pariset E, Cekanaviciute E, Costes SV NAR Cancer. 2021 Dec 22;3(4):zcab046.

[02/15/2022]
Summary:

Radiation-induced foci (RIF), which are nuclear puncta visualized by immunostaining of proteins, have been used as a surrogate marker of DNA double strand breaks (DSB) for the past 25 years. RIF formation and foci baseline have great potential to predict in vivo responses to ionizing radiation, predisposition to cancer and probability of adverse reactions to radiotherapy. In this review, we discuss the spatiotemporal characteristics of RIF after irradiation, addressing the common confounding factors, including cell proliferation and foci merging. We also summarize mathematical models to interpret RIF formation and resolution. This article was intended to guide the scientific community design radiobiology experiments using RIF as a key metric and to provide the necessary background for accurate biological interpretation.


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Effects of low-dose oxygen ions on cardiac function and structure in female C57BL/6J mice

Nemec-Bakk AS, Sridharan V, Landes RD, Singh P, Cao M, Dominic P, Seawright JW, Chancellor JC, Boerma M. Life Sci Space Res (Amst). 2022 Feb;32:105-12.

[02/07/2022]
Summary:

Research on cardiovascular effects of simulated space radiation has thus far been performed in male animal models. In the current study, long-term effects of single low doses of oxygen ion radiation on the heart was studied in adult female C57BL/6J mice. Irradiation caused remodeling of existing collagens in the heart and an increase in left ventricular levels of the T-cell marker CD2, but these did not result in significant changes in cardiac function. Future studies need to make direct comparisons between male and female animals in radiation effects on the heart.


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Robbing Peter to pay Paul: Competition for radiogenic breaks during rejoining diminishes curvature in the dose response for simple chromosome exchanges

Shuryak I, Loucas BD, Cornforth MN. Radiat Res. 2021 Aug 1;196(2):147-55. [1/29/2022]

[01/29/2022]
Summary:

The large majority of chromosome damage produced by ionizing radiations takes the form of exchange aberrations. For simple exchanges between two chromosomes, multi-fluor fluorescence in situ hybridization (mFISH) studies confirm that the dose response to X rays or gamma rays is quasilinear with dose. This result is in seeming conflict with generalized theories of radiation action that depend on the interaction of lesions as the source of curvature in dose-response relationships. A qualitative explanation for such "linearization" had been previously proposed but lacked quantitative support. The essence of this explanation is that during the rejoining of radiogenic chromosome breaks, competition for breaks (CFB) between different aberration types often results in formation of complex exchange aberrations at the expense of simple reciprocal exchange events. This process becomes more likely at high radiation doses, where the number of contemporaneous breaks is high and complex exchanges involving multiple breaks become possible. Here we provide mathematical support for this CFB concept under the assumption that the mean and variance for exchange complexity increase with radiation dose.


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Long-term sex- and genotype-specific effects of 56Fe irradiation on wild-type and APPswe/PS1dE9 transgenic mice.

Schroeder MK, Liu B, Hinshaw RG, Park MA, Wang S, Dubey S, Liu GG, Shi Q, Holton P, Reiser V, Jones PA, Trigg W, Di Carli MF, Caldarone BJ, Williams JP, O'Banion MK, Lemere CA.  [1/18/2022]

 Int J Mol Sci. 2021 Dec 10;22(24):13305.

[01/18/2022]
Summary:

There is evidence that 56Fe irradiation, a significant component of space radiation, may be more harmful to males than to females and worsen Alzheimer's disease pathology in genetically vulnerable models. We irradiated 4-month-old male and female, wild-type and Alzheimer's-like APP/PS1 mice with 0, 0.10, or 0.50 Gy of 56Fe ions (1GeV/u). Mice underwent microPET scans before and 7.5 months after irradiation, a battery of behavioral tests at 11 months of age and were sacrificed for pathological and biochemical analyses at 12 months of age. 56Fe irradiation worsened amyloid-beta (Aβ) pathology, gliosis, neuroinflammation and spatial memory, but improved motor coordination, in male transgenic mice and worsened fear memory in wild-type males. These results provide evidence for sex-specific, long-term CNS effects of space radiation.


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Ferroptosis, a new form of cell death defined after radiation exposure.

Zhang X, Li X, Zheng C, Yang C, Zhang R, Wang A, Feng J, Hu X, Chang S, Zhang H. Int J Radiat Biol. 2022 Jan 4;1-9. Online ahead of print. [1/18/2022]

[01/18/2022]
Summary:

Ionizing radiation induces an increase in hydroxyl radicals, free iron, and lipid metabolic enzymes, which subsequently synergistically initiate a high level of lipid peroxidation, making ionizing radiation an exogenous inducer of ferroptosis. In addition, ferroptosis may be the primary form of cell death in the bone marrow under hematopoietic acute radiation syndrome. Ionizing radiation can also induce changes in iron metabolism, which may be a target for regulating ferroptosis. Finally, ionizing radiation-induced ferroptosis initiates from the cytoplasm and ends on the membrane, and is independent of DNA damage.


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First measurements of low-energy cosmic rays on the surface of the lunar farside from Chang'E-4 mission

Pengwei Luo, Xiaoping Zhang, Shuai Fu, Yong Li, Cunhui Li, Jinbin Cao and published in SCIENCE ADVANCES • 14 Jan 2022 • Vol 8, Issue 2

[01/18/2022]
Summary:

The radiation environment on the lunar surface is strongly affected by cosmic rays and the albedo particles produced by their interactions with the lunar surface. However, the data of the cosmic ray energy spectra is still absent to date. To better evaluate the radiation level, measurements of the cosmic ray energy spectra on the lunar surface are paramount. In this work, we obtained the energy spectra of cosmic ray protons, alpha particles, CNO, and heavy ions with energies ranging from ~10 MeV/nuc to ~100 MeV/nuc based on the data collected by the Lunar Lander Neutron and Dosimetry (LND) instrument onboard the Chang’E-4 (CE-4) lander around the solar minimum 24/25.
The comparisons of the CE-4/LND measurements to those observations from several near-earth spacecraft, such as the ACE, the SOHO, and the STEREO-A, show that they were consistent within 1.7 standard deviations, indicating that the influence of the lunar surroundings, like magnetic anomalies, on these energy spectra is negligible. Considering that the higher energy particles are less sensitive to the lunar surroundings, this conclusion can be further extended to the higher energy spectra of these particles. We also extracted the He isotope ratios and a prominent enhancement was observed at ~12 MeV/nuc. In addition, the dawn-dusk symmetry of the energy spectrum was confirmed, which will guide the selections of landing times for future crewed lunar missions and extravehicular activities on the lunar surface. In short, the above findings will promote human understanding of the lunar radiation environment and benefit future lunar explorations.


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Mitochondrial effects in the liver of C57BL/6 mice by low dose, high energy, high charge irradiation

Barnette BL, Yu Y, Ullrich RL, Emmett MR. Int J Mol Sci. 2021 Nov;22(21):11806. [12/20/2021]

[12/20/2021]
Summary:

This publication is the first full multi-omics, systems biological study (encompassing transcriptomics, proteomics, lipidomics, metabolomics and specific biological assays) to monitor the microenvironmental changes induced by low-dose high-charge, high-energy (HZE) exposure in C57BL/6 mouse liver. These studies were performed to study microenviromental changes induced by low-dose HZE leading to hepatocellular carcinoma (HCC). The C57BL/6 mouse is relatively resistant to low-dose HZE induced HCC and thus, it was unexpected to observe the mitochondrial dysfunction in their livers after low-dose HZE exposure. The HZE induced mitochondrial dysfunction was exhibited in all omics datasets (transcriptomics, proteomics, lipidomics & metabolomics) and was also validated through mitochondrial Complex I biochemical assays. Mitochondria effects induced by HZE irradiation are novel, real, and important to the health and safety of the astronauts. Not only in liver but these effects could also be very detrimental in brain and cardiac tissue that have high levels of mitochondria. The systems biological approach identified possible countermeasures that are targeted to specific biological pathways that are discussed as possible mediators of exposure to low-dose HZE.


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Track structure components: Characterizing energy deposited in spherical cells from direct and peripheral HZE ion hits

 Plante I, Poignant F, Slaba T., Life (Basel). 2021 Oct 20;11(11):1112.   [12/16/2021]

[12/16/2021]
Summary:

To understand the biological effects of radiation, it is important to determine how ionizing radiation deposits energy in micrometric targets. The energy deposited in a target located in an irradiated tissue is a function of several factors such as the radiation type and the irradiated volume size. We simulated the energy deposited by energetic ions in spherical targets of 1, 2, 4, and 8 µm radii encompassed in irradiated parallelepiped volumes of various sizes using the stochastic radiation track structure code Relativistic Ion Tracks (RITRACKS). Because cells are usually part of a tissue when they are irradiated, electrons originating from radiation tracks in neighboring volumes also contribute to energy deposition in the target. To account for this contribution, we used periodic boundary conditions in the simulations. We found that the single-ion spectra of energy deposition in targets comprises two components: the direct ion hits to the targets, which is identical in all irradiation conditions, and the contribution of hits from electrons from neighboring volumes, which depends on the irradiated volume. We also calculated an analytical expression of the indirect hit contributions using the local effect model, which showed results similar to those obtained with RITRACKS.


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Cell Survival Computation via the Generalized Stochastic Microdosimetric Model (GSM2); Part I: The Theoretical Framework

Francesco G. Cordoni;  Marta Missiaggia;  Emanuele Scifoni;  Chiara La Tessa Radiat Res (2022) 197 (3): 218–232.

[12/02/2021]
Summary:

This article presents the Generalized Stochastic Microdosimetric Model (GSM2) for computing explicitly a cell survival curve. GSM2 is a general probabilistic model that predicts the kinetic evolution of DNA damages taking full advantage of a microdosimetric description of a radiation energy deposition.


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Effects of dietary aspirin on high-LET radiation-induced prostaglandin E2 levels and gastrointestinal tumorigenesis in Apc1638N/+ mice

Suman S, Kumar S, Moon BH, Angdisen J, Kallakury BVS, Datta K, Fornace AJ Jr. and published in Life Sci Space Res (Amst). 2021 Nov;31:85-91.

[11/13/2021]
Summary:

Exposure to high-LET heavy-ions during deep space missions will probably increase gastrointestinal (GI)-cancer mortality risk for astronauts, and by one estimate may exceed the current NASA’s limit of < 3% REID (Radiation exposure-induced death) from cancer. Development of a safe and effective countermeasure agent against heavy-ion radiation induced GI-tumorigenesis would be of obvious benefit – particularly if chronic use is well tolerated. For example, multiple studies have reported reduced colorectal cancer incidence with chronic aspirin intake. Previously, we reported that upregulation of cyclooxygenase-2/prostaglandin E2 (COX2/PGE2) signaling coincides with persistent inflammation and GI-tumorigenesis after heavy-ion radiation exposure. Therefore, aspirin, a well-known inhibitor of the COX/PGE2 pathway, was evaluated as a potential countermeasure against heavy ion-induced GI- tumorigenesis using a surrogate mouse model of human GI cancer i.e. Apc1638N/+ mice. Animals were fed either standard or aspirin supplemented diet starting at 4 weeks of age until the end of the study. After one month on the aspirin diet, mice were exposed to heavy-ion (28Si-ion) radiation, and intestinal tumor number, cluster, size, and serum PGE2 levels were analyzed. Aspirin led to a significant reduction in serum PGE2, however, aspirin did not reduce heavy-ion induced GI-tumorigenesis. In summary, this study suggests that aspirin is not effective in the prevention of heavy-ion induced GI-tumorigenesis. While COX2/PGE2 signaling was reduced by aspirin, our study indicates that other cancer-associated pathways can drive HZE ion tumorigenesis.


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Human mesenchymal stromal cells maintain their stem cell traits after high-LET particle irradiation - Potential implications for particle radiotherapy and manned space missions

Rühle A, Ping D, Lopez Perez R, Strack M, Brons S, Yijia Q, Debus J, Wuchter P, Grosu AL, Huber PE, Nicolay NH. and published in Cancer Lett. 2022 Jan;524:172-81. Available online 21 October 2021.

[11/13/2021]
Summary:

The influence of high-linear energy transfer (LET) particle radiation on the functionalities of mesenchymal stromal cells (MSCs) is largely unknown. Here, we analyzed the effects of proton (1H), helium (4He), carbon (12C) and oxygen (16O) ions on human bone marrow-MSCs. Cell cycle distribution and apoptosis induction were examined by flow cytometry, and DNA damage was quantified using ?H2AX immunofluorescence and Western blots. Relative biological effectiveness values of MSCs amounted to 1.0–1.1 for 1H, 1.7–2.3 for 4He, 2.9–3.4 for 12C and 2.6–3.3 for 16O. Particle radiation did not alter the MSCs’ characteristic surface marker pattern, and MSCs maintained their multi-lineage differentiation capabilities. Apoptosis rates ranged low for all radiation modalities. At 24 h after irradiation, particle radiation-induced ATM and CHK2 phosphorylation as well as ?H2AX foci numbers returned to baseline levels. The resistance of human MSCs to high-LET irradiation suggests that MSCs remain functional after exposure to moderate doses of particle radiation as seen in normal tissues after particle radiotherapy or during manned space flights. In the future, in vivo models focusing on long-term consequences of particle irradiation on the bone marrow niche and MSCs are needed.


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Historical reconstruction of astronaut cancer risk: Context for recent solar minima

Slaba TC. Space Weather. 2021 Oct;19(10):e2021SW002851

[11/13/2021]
Summary:

Recent observational data and model predictions have suggested an intensifying galactic cosmic ray environment. This could have an impact on mission planning and crew safety as space exploration extends beyond low Earth orbit for longer durations. Updated models and data are evaluated in this work to provide historical context for recent observations. It is shown that projected risks vary by only +10% over all historical minima since 1750. This degree of historical variation is within combined environmental and physics uncertainties already accounted for in the probabilistic cancer risk model used by NASA for crew health and safety considerations. Uncertainties for epidemiology and radiobiology models remain significantly larger than combined physics uncertainties; however, new measurement data and model development efforts should continue to be supported by NASA and international partners to improve our understanding of the space environment.


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Mortality from leukemia, cancer and heart disease among U.S. nuclear power plant workers, 1957-2011

Boice JD Jr, Cohen SS, Mumma MT, Hagemeyer DA, Chen H, Golden AP, Yoder RC, Dauer LT.

Int J Radiat Biol. 2021 Oct 20;1-67. Online ahead of print.

[11/10/2021]
Summary:

The aim of the Million Person Study (MPS) of Low Dose Health Effects is to examine the level of radiation risk for chronic exposures received gradually over time and not acutely as was the case for the Japanese atomic bomb survivors. Leukemia, selected cancers, Parkinson's disease, ischemic heart disease (IHD) and other causes of death are evaluated. Prolonged exposure to radiation increased the risk of leukemia other than CLL among NPP workers. There was little evidence for a radiation-association for all solid cancers, lung cancer or ischemic heart disease. Increased precision will be forthcoming as the different cohorts within the MPS are combined, such as industrial radiographers and medical radiation workers who were assembled and evaluated in like manner.


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Improving astronaut cancer risk assessment from space radiation with an ensemble model framework

Simonsen LC, Slaba TC and published in Life Sci Space Res (Amst). 2021 Nov;31:14-28.

[11/10/2021]
Summary:

A new approach to NASA space radiation risk modeling has successfully extended the current NASA probabilistic cancer risk model to an ensemble framework able to consider sub-model parameter uncertainty as well as model-form uncertainty associated with differing theoretical or empirical formalisms. Applying ensemble methodologies to space radiation risk projections offers the potential to efficiently incorporate emerging research results, allow for the incorporation of future models, improve uncertainty quantification, and reduce the impact of subjective bias. In these analyses, the ensemble forecast compares well to results from NASA’s current operational cancer risk projection model used to assess permissible mission durations for astronauts. However, a large range of projected risk values are obtained at the upper 95th confidence level where models must extrapolate beyond available biological data sets.


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Examining the Effects of 4He Exposure on the Gut-Brain Axis

Carli B. Jones; Lauren B. Peiffer; Catherine M. Davis; Karen S. Sfanos Radiat Res (2022) 197 (3): 242–252.

[11/09/2021]
Summary:

There is limited research investigating the early effects of helium ion (4He) exposure on the gut-brain axis. We studied changes in GI microbiota and social odor recognition memory of rats acutely exposed to 4He (0, 5 or 25 cGy, 250 MeV/n). At 7 days following exposure, 25 cGy 4He resulted in deficits in social recognition memory, decreases in Akkermansia spp. and spore-forming bacteria, and changes in serotonin production within the intestine, without pathological changes to the GI tissues. These results suggest that the gut-brain axis can be disrupted following simulated space radiation exposure and have implications for astronaut health during exploratory class missions.


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Multi-domain touchscreen-based cognitive assessment of C57BL/6J female mice shows whole-body exposure to 56Fe particle space radiation in maturity improves discrimination learning yet impairs stimulus

Soler I, Yun S, Reynolds RP, Whoolery CW, Tran FH, Kumar PL, Rong Y, DeSalle MJ, Gibson AD, Stowe AM, Kiffer FC, Eisch AJ. Front Behav Neurosci. 2021 Oct 11;15:722780. Online ahead of print.

[11/08/2021]
Summary:

Astronauts during interplanetary missions will be exposed to galactic cosmic radiation, including charged particles like 56Fe. Most preclinical studies with mature, "astronaut-aged" rodents suggest space radiation diminishes performance in classical hippocampal- and prefrontal cortex-dependent tasks. However, a rodent cognitive touchscreen battery unexpectedly revealed 56Fe radiation improves the performance of C57BL/6J male mice in a hippocampal-dependent task (discrimination learning) without changing performance in a striatal-dependent task (rule-based learning). As there are conflicting results on whether the female rodent brain is preferentially injured by or resistant to charged particle exposure, and as the proportion of female vs. male astronauts is increasing, further study on how charged particles influence the touchscreen cognitive performance of female mice is warranted. We hypothesized that, similar to mature male mice, mature female C57BL/6J mice exposed to fractionated whole-body 56Fe irradiation (3 × 6.7cGy 56Fe over 5 days, 600 MeV/n) would improve performance vs. Sham conditions in touchscreen tasks relevant to hippocampal and prefrontal cortical function [e.g., location discrimination reversal (LDR) and extinction, respectively]. In LDR, 56Fe female mice more accurately discriminated two discrete conditioned stimuli relative to Sham mice, suggesting improved hippocampal function. However, 56Fe and Sham female mice acquired a new simple stimulus-response behavior and extinguished this acquired behavior at similar rates, suggesting similar prefrontal cortical function. Based on prior work on multiple memory systems, we next tested whether improved hippocampal-dependent function (discrimination learning) came at the expense of striatal stimulus-response rule-based habit learning (visuomotor conditional learning). Interestingly, 56Fe female mice took more days to reach criteria in this striatal-dependent rule-based test relative to Sham mice. Together, our data support the idea of competition between memory systems, as an 56Fe-induced decrease in striatal-based learning is associated with enhanced hippocampal-based learning. These data emphasize the power of using a touchscreen-based battery to advance our understanding of the effects of space radiation on mission critical cognitive function in females, and underscore the importance of preclinical space radiation risk studies measuring multiple cognitive processes, thereby preventing NASA's risk assessments from being based on a single cognitive domain.


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Mitigation of late cardiovascular effects of oxygen ion radiation by γ-tocotrienol in a mouse model

Nemec-Bakk AS, Sridharan V, Landes RD, Singh P, Cao M, Seawright JW, Liu X, Zheng G, Dominic P, Pathak R, Boerma M. Life Sci Space Res (Amst). 2021 Nov;31:43-50

[11/08/2021]
Summary:

γ-tocotrienol is an anti-oxidant, modifies cholesterol metabolism, and has anti-inflammatory and endothelial cell protective properties. This study shows that γ-tocotrienol mitigated effects of oxygen ion irradiation on cardiac function and structure in a mouse model, suggesting that γ-tocotrienol has potential as a countermeasure against degenerative tissue effects of high-LET radiation on the heart.


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Non-targeted effects of radiation: A personal perspective on the role of exosomes in an evolving paradigm

Kadhim M, Tuncay Cagatay S, Elbakrawy EM. and published in Int J Radiat Biol. 2021 Oct 18:1-39. Online ahead of print. 

[11/02/2021]
Summary:

Radiation-induced “non-targeted effects” (NTE) have implications in a variety of areas relevant to radiation biology. Here we evaluate the various cargoes associated with exosomal signalling and how they work synergistically to initiate and propagate the non-targeted effects including genomic instability and bystander effects. Extracellular vesicles (EV), in particular exosomes, have been shown to carry bystander signals. Exosome cargo may contain nucleic acids, both DNA and RNA, as well as proteins, lipids, and metabolites. These cargo molecules have all been considered as potential mediators of NTE. A review of current literature shows mounting evidence of a role for ionizing radiation in modulating both the numbers of exosomes released from affected cells as well as the content of their cargo, and that these exosomes can instigate functional changes in recipient cells. However, there are significant gaps in our understanding, particularly regarding modified exosome cargo after radiation exposure and the functional changes induced in recipient cells. Also, there are a number of interesting research questions relating to the whole EV field and not limited to radiation biology. Finding answers to these questions may lead to novel therapies, prognostic and diagnostic biomarkers, and an enhanced understanding of intercellular communication.


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A Geant4-DNA evaluation of radiation-induced DNA damage on a human fibroblast

Shin WG, Sakata D, Lampe N, Belov O, Tran NH, Petrovic I, Ristic-Fira A, Dordevic M, Bernal MA, Bordage MC, Francis Z, Kyriakou I, Perrot Y, Sasaki T, Villagrasa C, Guatelli S, Breton V, Emfietzoglou D, Incerti S. Cancers (Basel). 2021 Oct;13(19):4940

[10/30/2021]
Summary:

Accurate modeling of the radiobiological mechanisms responsible for the induction of DNA damage remains a major scientific challenge. In this work, the assessment of DNA damage in a human fibroblast cell using the Geant4-DNA Monte Carlo toolkit is described. A validation study using a computational geometric model of human DNA was performed and the calculated DNA damage as a function of particle type and energy is presented. The results of this work showed a significant improvement over previous work and are consistent with recent radiobiological experimental data, such as damage yields. The complete simulation chain application "molecularDNA", an example for users of Geant4-DNA, will soon be distributed through Geant4.


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Predicting space radiation single ion exposure in rodents: A machine learning approach

Prelich MT, Matar M, Gokoglu SA, Gallo CA, Schepelmann A, Iqbal AK, Lewandowski BE, Britten RA, Prabhu RK, Myers JG Jr.and published in Front Syst Neurosci. 2021 Oct 15;15:715433

[10/30/2021]
Summary:

This study presents a data-driven machine learning approach to predict individual Galactic Cosmic Radiation (GCR) ion exposure for 4He, 16O, 28Si, 48Ti, or 56Fe up to 150 mGy, based on Attentional Set-shifting (ATSET) experimental tests. The analysis employs scores of selected input features and different normalization approaches which yield varying degrees of model performance. The current study shows that support vector machine, Gaussian naive Bayes, and random forest models are capable of predicting individual ion exposure using ATSET scores where corresponding Matthews correlation coefficients and F1 scores reflect model performance exceeding random chance. The study suggests a decremental effect on cognitive performance in rodents due to ≤150 mGy of single ion exposure, inasmuch as the models can discriminate between 0 mGy and any exposure level in the performance score feature space.


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Genomic changes driven by radiation-induced DNA damage and microgravity in human cells

Beheshti A, McDonald JT, Hada M, Takahashi A, Mason CE, Mognato M. and published in Int J Mol Sci. 2021 Oct;22(19):10507. Review

[10/30/2021]
Summary:

The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of space radiation carcinogenesis. Therefore, in view of future missions to the Moon and Mars, there is an urgent need to estimate as accurately as possible the individual risk from space exposure to improve the safety of space exploration. In this review, we survey the combined effects from the two main physical components of the space environment, ionizing radiation and microgravity, to alter the genetics and epigenetics of human cells, considering both real and simulated space conditions. Data collected from studies on human cells are discussed for their potential use to estimate individual radiation carcinogenesis risk from space exposure.


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The impact of deep space radiation on cognitive performance: From biological sex to biomarkers to countermeasures

Krukowski K, Grue K, Becker M, Elizarraras E, Frias ES, Halvorsen A, Koenig-Zanoff M, Frattini V, Nimmagadda H, Feng X, Jones T, Nelson G, Ferguson AR, Rosi S Sci Adv. 2021 Oct 15;7(42):eabg6702.

[10/25/2021]
Summary:

These studies demonstrate sex-dimorphic responses in mice exposed to accelerated charged particles to simulate GCR (GCRsim); males displayed impaired spatial learning, whereas females did not. Mechanistically, these GCRsim-induced learning impairments corresponded with chronic microglia activation and synaptic alterations in the hippocampus. Temporary microglia depletion shortly after GCRsim exposure mitigated GCRsim-induced deficits measured months after the radiation exposure. Furthermore, blood monocyte levels measured early after GCRsim exposure were predictive of the late learning deficits and microglia activation measured in the male mice.


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Machine learning models to predict cognitive impairment of rodents subjected to space radiation

Matar M, Gokoglu SA, Prelich MT, Gallo CA, Iqbal AK, Britten RA, Prabhu RK, Myers JG Jr Front Syst Neurosci. 2021 Sep 13;15:713131.

[10/18/2021]
Summary:

This research uses machine-learned computational analyses to predict the cognitive performance impairment of rats induced by irradiation. The experimental data in the analyses is from a rodent model exposed to = 15 cGy of individual Galactic Cosmic Radiation (GCR) ions: 4He, 16O, 28Si, 48Ti, or 56Fe, expected for a Lunar or Mars mission. Here, the worst performing rats of the control group define the impairment thresholds based on population analyses via cumulative distribution functions, leading to the labeling of impairment for each subject. On a subject-based level, implementing Machine Learning (ML) classifiers such as the Gaussian Naïve Bayes, Support Vector Machine, and Artificial Neural Networks identifies rats that have a higher tendency for impairment after GCR exposure. One key finding of our study is that prescreen performance scores can be used as multidimensional input features to predict each rodent's susceptibility to cognitive impairment due to space radiation exposure. This result is significant to crewed space missions as it supports the potential of predicting an astronaut's impairment in a specific task before spaceflight through the implementation of appropriately trained ML tools.


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Effects of 5-ion beam irradiation and hindlimb unloading on metabolic pathways in plasma and brain of behaviorally tested WAG/Rij rats

Raber J, Holden S, Sudhakar R, Hall R, Glaeser B, Lenarczyk M, Rockwell K, Nawarawong N, Sterrett J, Perez R, Leonard SW, Morré J, Choi J, Kronenberg A, Borg A, Kwok A, Stevens JF, Olsen CM, Willey JS, Bobe G, Baker J. Front Physiol. 2021 Sep 27;12:746509

[10/04/2021]
Summary:

A limitation of simulated space radiation studies is that radiation exposure is not the only environmental challenge astronauts face during missions. Therefore, we characterized behavioral and cognitive performance of male WAG/Rij rats 3 months after sham irradiation or total body irradiation with a simplified 5-ion mixed beam exposure in the absence or presence of simulated weightlessness using hindlimb unloading (HU) alone. Six months following behavioral and cognitive testing or 9 months following sham-irradiation or total body irradiation, plasma and brain tissues (hippocampus and cortex) were processed to determine whether the behavioral and cognitive effects were associated with long-term alterations in metabolic pathways in plasma and brain. Sham HU, but not irradiated HU, rats were impaired in spatial habituation learning. Rats irradiated with 1.5 Gy showed increased depressive-like behaviors. This was seen in the absence but not presence of HU. Thus, HU has differential effects in sham irradiated and irradiated animals and specific behavioral measures are associated with plasma levels of distinct metabolites 6 months later. The combined effects of HU and radiation on metabolic pathways in plasma and brain illustrate the complex interaction of environmental stressors and highlights the importance of assessing these interactions.


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Genomic changes driven by radiation-induced DNA damage and microgravity in human cells

Beheshti A, McDonald JT, Hada M, Takahashi A, Mason CE, Mognato M. Int J Mol Sci. 2021 Sep;22(19):10507. Review.

[10/04/2021]
Summary:

The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of space radiation carcinogenesis. Therefore, in view of future missions to the Moon and Mars, there is an urgent need to estimate as accurately as possible the individual risk from space exposure to improve the safety of space exploration. In this review, we survey the combined effects from the two main physical components of the space environment, ionizing radiation and microgravity, to alter the genetics and epigenetics of human cells, considering both real and simulated space conditions. Data collected from studies on human cells are discussed for their potential use to estimate individual radiation carcinogenesis risk from space exposure.


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Exposure to low (≤10 cGy) doses of 4He particles leads to increased social withdrawal and loss of executive function performance.

Burket JA, Matar M, Fesshaye A, Pickle JC, Britten RA.Radiat Res. 2021 Oct 1;196(4):345-54.Burket JA, Matar M, Fesshaye A, Pickle JC, Britten RA.Radiat Res. 2021 Oct 1;196(4):345-54.

[10/01/2021]
Summary:

This study is the first to report that ≤10 cGy of 4He particles leads to a significant impairment of two advanced executive functions, constrained cognitive flexibility (ATSET assay) and insightful problem solving (UCFleX). The nature (loss of simple discrimination performance) and frequency of neurocognitive loss were very similar to that observed when higher Z(LET) particles were used, suggesting little LET dependency for executive function impairment.
Executive functions are also critical in regulating psychosocial activities. We thus established that exposure to 5 cGy of He, led to high levels of social withdrawal (within freely interacting dyads). The He-exposed rats have a significantly higher incidence and duration of self-grooming than did shams, which was even more surprising given that their dyad partners were able to physically interact with the irradiated rats (touching/climbing over them). Some individuals in confinement studies such as the Mars 500 study did socially withdraw (Basner et al, 2014), so there is a possibility that space radiation exposure could exacerbate such withdrawals.


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Contemporary biomedical engineering perspective on volitional evolution for human radiotolerance enhancement beyond low-Earth orbit

Borg AM, Baker JE. Synth Biol (Oxf). 2021 Sep 2;6(1):ysab023.

[09/27/2021]
Summary:

Despite developments in the prediction of and protection against radiation events beyond Earth's protective magnetosphere, sustained astronaut exposure to cosmic radiation events remains unavoidable. This danger is a primary focus of NASA when expanding humankind's presence to Mars and beyond. The authors identify various genes which are known to confer radioprotection, and discuss current technological and ethical limitations in incorporating them into astronauts. Even if allowed and perfected, genetic engineering for radiation protection would still necessitate additional solutions for comprehensive safety; some possibilities discussed include synthetic torpor and advanced propulsion systems.


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Space radiation protection countermeasures in microgravity and planetary exploration

Montesinos CA, Khalid R, Cristea O, Greenberger JS, Epperly MW, Lemon JA, Boreham DR, Popov D, Gorthi G, Ramkumar N, Jones JA. Life (Basel). 2021 Aug 14;11(8):829. Review.

[09/23/2021]
Summary:

We summarize the current state of knowledge regarding potential means to reduce the biological effects of space radiation. New countermeasure strategies for exploration-class missions are proposed, based on recent advances in nutrition, pharmacologic, and immune science.


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Destabilizing effects of ionizing radiation on chromosomes: Sizing up the damage

Cornforth MN, Bedford JS, Bailey SM and published in Cytogenet Genome Res. 2021 Sep 6;1-24. Review.

[09/23/2021]
Summary:

For long-term survival and evolution, all organisms have depended on a delicate balance between processes involved in maintaining stability of their genomes and opposing processes that lead toward destabilization. At the level of mammalian somatic cells in renewal tissues, events or conditions that can tip this balance toward instability have attracted special interest in connection with carcinogenesis. Mutations affecting DNA (and its subsequent repair) would, of course, be a major consideration here. These may occur spontaneously through endogenous cellular processes or as a result of exposure to mutagenic environmental agents. It is in this context that we discuss the rather unique destabilizing effects of ionizing radiation (IR) in terms of its ability to cause large-scale structural rearrangements to the genome. We present arguments supporting the conclusion that these and other important effects of IR originate largely from microscopically visible chromosome aberrations.


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The combined effect of simulated microgravity and radiation on chromosome aberrations in human peripheral blood lymphocytes

Yamanouchi S, Adachi T, Yoshida Y, Rhone J, Mao J-H, Fujiwara K, Saganti PB, Takahashi A, Hada M. Biological Sciences in Space. 2021;35:15-23.

[09/23/2021]
Summary:

We investigated the combined effect of µG and space radiation on human peripheral blood lymphocytes. Whole blood was irradiated with X-ray or carbon-ion (C-ion) beam while being exposed to simulated µG using a three-dimensional clinostat. The frequency of chromosome aberrations (CA) was assessed using the three-color fluorescence in situ hybridization on chromosome spreads of Colcemid-induced prematurely condensed chromosomes in lymphocytes during the first cell division post irradiation. Compared with the cells irradiated at 1G, the frequency of CA was increased in cells simultaneously exposed to simulated µG and radiation. This result is similar to those of our previous studies in which we used human lymphoblast TK6 cells and human fibroblast IBR-hTERT cells.


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Radiation countermeasures for hematopoietic acute radiation syndrome: Growth factors, cytokines and beyond

Singh VK, Seed TM. in Int J Radiat Biol. 2021 Aug 17;1-67. Review.

[08/30/2021]
Summary:

This article reports the status of pharmaceuticals currently being developed for possible use for individuals unwantedly and acutely injured as a result of radiological/nuclear exposures. A limited number of medicinals (namely filigrastim, pegfiligrastim, sargramostim and romiplostim) have been deemed sufficiently safe and effective by the US FDA for use in treating the ‘hematopoietic acute radiation syndrome. All of these agents are recombinant growth factors that target and stimulate progenitors within bone marrow, thus serving to foster hematopoietic recovery following acute irradiation. Comparable medicinals for the other major sub-syndromes of ARS are currently lacking, but much needed. The research and development of such medicinals will undoubtedly entail some form of a polypharmaceutical strategy, or perhaps novel, bioengineered chimeric agents with multiple, radioprotective/radiomitigative functionalities.


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Protective Effects of Amino Acids on Plasmid DNA Damage Induced by Therapeutic Carbon Ions

Katsunori Yogo, Chieko Murayama, Ryoichi Hirayama, Ken-ichiro Matsumoto, Ikuo Nakanishi, Hiromichi Ishiyama, Hiroshi Yasuda Radiation Research, 196(2), 197-203, (27 May 2021)

[08/25/2021]
Summary:

With the aim of finding the most effective radioprotector against heavy ions, we investigated systematically the radioprotective effects of five amino acids: tryptophan (Trp), cysteine (Cys), methionine (Met), valine (Val) and alanine (Ala) on the damage yields of plasmid DNA. The samples were irradiated with 290 MeV/u carbon-ion beams on spread-out Bragg peak at HIMAC, Japan. As results, some amino acids such as Trp, Cys and Met showed good radioprotective effects in regard to the double strand breaks of plasmid DNA. It was indicated that the radioprotective effects against carbon ions could be explained primarily based on the scavenging capacity of radiation-induced radicals.


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A proposed change to astronaut exposures limits is a giant leap backwards for radiation protection

Francis A. Cucinotta, Walter Schimmerling, Eleanor A. Blakely, Tom K. Hei, Life Sciences in Space Research, 31, 2021, 59-70,ISSN 2214-5524

[08/16/2021]
Summary:

A recent NAS report, in an effort to minimize differences in age and sex on flight opportunities, suggests a 600 mSv career effective dose limit based on a median estimate to reach 3% cancer fatality for 35-year old females. The NAS report does not call out examples where females would be excluded from space missions planned in the current decade using the current radiation limits at NASA. In addition, there are minimal considerations of the level of risk to be encountered at this exposure level with respect to the uncertainties of heavy ion radiobiology, and risks of cancer, as well as cognitive detriments and circulatory diseases. Furthermore, their recommendation to limit Sieverts and not risk in conjunction with a waiver process is essentially a recommendation to remove radiation limits for astronauts. We discuss issues with several of the NAS recommendations with the conclusion that the recommendations could have negative impacts on crew health and safety, and violate the three principles of radiation protection (to prevent clinically significant deterministic effects, limit stochastic effects, and practice ALARA), which would be a giant leap backwards for radiation protection.


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Space Radiation Dosimetry at the Exposure Facility of the International Space Station for the Tanpopo Mission

Kodaira S, Naito M, Uchihori Y, Hashimoto H, Yano H, Yamagishi A. Astrobiology. 2021 Aug 4.. doi: 10.1089/ast.2020.2427. Epub ahead of print. PMID: 34348047.

[08/14/2021]
Summary:

Radiation dosimetry was carried out at the exposure facility (EF) and the pressurized module (PM) of the Japanese Kibo module installed in the International Space Station as one study on environmental monitoring for the Tanpopo mission. Three exposure panels and three references including biological and organic samples and luminescence dosimeters were launched to obtain data for different exposure durations during 3 years from May 2015 to July 2018. The dosimeters were equipped with additional shielding materials (0.55, 2.95, and 6.23 g/cm2 mass thickness). The relative dose variation, as a function of shielding mass thickness, was observed and compared with Monte Carlo simulations with respect to galactic cosmic rays (GCRs) and typical solar energetic particles (SEPs). The mean annual dose rates were DEF = 231 ± 5 mGy/year at the EF and DPM = 82 ± 1 mGy/year at the PM during the 3 years. The PM is well shielded, and the GCR simulation indicated that the measured mean dose reduction ratio inside the module (DPM/DEF = 0.35) required ~26 g/cm2 additional shielding mass thickness. Observed points of the dose reduction tendency could be explained by the energy ranges of protons (10-100 MeV), where the protons passed through, or were absorbed in, the shielding materials of different mass thickness that surrounded dosimeters.


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Space radiation-induced alterations in the hippocampal ubiquitin-proteome system

Tidmore A, Dutta SM, Fesshaye AS, Russell WK, Duncan VD, Britten RA. Int J Mol Sci. 2021 Jul 19;22(14):7713.

[08/09/2021]
Summary:

Exposure of rodents to <20 cGy Space Radiation (SR) impairs performance in several hippocampus-dependent cognitive tasks, including spatial memory. However, there is considerable inter-individual susceptibility to develop SR-induced spatial memory impairment. In this study, a robust label-free mass spectrometry (MS)-based unbiased proteomic profiling approach was used to characterize the composition of the hippocampal proteome in adult male Wistar rats exposed to 15 cGy of 1 GeV/n 48Ti and their sham counterparts. Unique protein signatures were identified in the hippocampal proteome of: (1) sham rats, (2) Ti-exposed rats, (3) Ti-exposed rats that had sham-like spatial memory performance, and (4) Ti-exposed rats that impaired spatial memory performance. Approximately 14% (159) of the proteins detected in hippocampal proteome of sham rats were not detected in the Ti-exposed rats. We explored the possibility that the loss of the Sham-only proteins may arise as a result of SR-induced changes in protein homeostasis. SR-exposure was associated with a switch towards increased pro-ubiquitination proteins from that seen in Sham. These data suggest that the role of the ubiquitin-proteome system as a determinant of SR-induced neurocognitive deficits needs to be more thoroughly investigated.


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Associations between lipids in selected brain regions, plasma miRNA, and behavioral and cognitive measures following 28Si ion irradiation
Minnier J, Emmett MR, Perez R, Ding LH, Barnette BL, Larios RE, Hong C, Hwang TH, Yu Y, Fallgren CM, Story MD, Weil MM, Raber J. Sci Rep. 2021 Jul 21;11(1):14899. [07/31/2021]
Summary:
To develop biomarkers of the space radiation response, BALB/c and C3H female and male mice and their F2 hybrid progeny were irradiated with 28Si ions (350 MeV/n, 0.2 Gy) and tested for behavioral and cognitive performance 1, 6, and 12 months following irradiation. There were associations between lipids in select brain regions, plasma miRNA, and cognitive measures and behavioral following 28Si ion irradiation. Different but overlapping sets of miRNAs in plasma were found to be associated with cognitive measures and behavioral in sham and irradiated mice at the three time points. The radiation condition revealed pathways involved in neurodegenerative conditions and cancers. Relationships were also revealed with CD68 in miRNAs in an anatomical distinct fashion, suggesting that distinct miRNAs modulate neuroinflammation in different brain regions. The associations between lipids in selected brain regions, plasma miRNA, and behavioral and cognitive measures following 28Si ion irradiation could be used for the development of biomarker of the space radiation response.
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Transcriptomic analysis links hepatocellular carcinoma (HCC) in HZE ion irradiated mice to a human HCC subtype with favorable outcomes
Ding LH, Yu Y, Edmondson EF, Weil MM, Pop LM, McCarthy M, Ullrich RL, Story MD. Sci Rep. 2021 Jul 7; 11(1): 14052 [07/20/2021]
Summary:
High-charge, high-energy ion particle (HZE) radiations are extraterrestrial in origin and characterized by high linear energy transfer (high-LET), which causes more severe cell damage than low-LET radiations like γ-rays or photons. High-LET radiation poses potential cancer risks for astronauts on deep space missions, but the studies of its carcinogenic effects have relied heavily on animal models. It remains uncertain whether such data are applicable to human disease. Here, we used genomics approaches to directly compare high-LET radiation-induced, low-LET radiation-induced and spontaneous hepatocellular carcinoma (HCC) in mice with a human HCC cohort from The Cancer Genome Atlas (TCGA). We identified common molecular pathways between mouse and human HCC and discovered a subset of orthologous genes (mR-HCC) that associated high-LET radiation-induced mouse HCC with a subgroup (mrHCC2) of the TCGA cohort. The mrHCC2 TCGA cohort was more enriched with tumor-suppressing immune cells and showed a better prognostic outcome than other patient subgroups.
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Cancer incidence and mortality in the USA Astronaut Corps, 1959-2017
Reynolds R, Little MP, Day S, Charvat J, Blattnig S, Huff J, Patel ZS. Occup Environ Med. 2021 May 26. Online ahead of print. [06/29/2021]
Summary:
Cancer incidence and mortality are important outcomes in the surveillance of long-term astronaut health. In this work, we compare cancer incidence rates, cancer-specific mortality rates, and cancer case-fatality ratios in US astronauts with those in the US general population. Overall cancer incidence and mortality were slightly lower than expected from national rates with SIR = 82 (95% CI=63-104) and SMR 72 (95% CI 44-111) with a modest 14% reduction in case-fatality ratio. We note a significant increase in incidence of melanoma that is consistent with that observed in aircraft pilots, suggesting this may be associated with ultraviolet radiation or lifestyle factors rather than any astronaut-specific exposure. Reductions in lung cancer incidence and mortality, and trends toward such reductions in colon cancer, may be explained in part by healthy lifestyle, as well as differential screening among astronauts.
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Evaluating the long-term effect of space radiation on the reproductive normality of mammalian sperm preserved on the International Space Station
Wakayama S, Ito D, Kamada Y, Shimazu T, Suzuki T, Nagamatsu A, Araki R, Ishikawa T, Kamimura S, Hirose N, Kazama K, Yang L, Inoue R, Kikuchi Y, Hayashi E, Emura R, Watanabe R, Nagatomo H, Suzuki H, Yamamori T, Tada MN, Osada I, Umehara M, Sano H, Kasahara H, Higashibata A, Yano S, Abe M, Kishigami S, Kohda T, Ooga M, Wakayama T. Sci Adv. 2021 Jun 11;7(24):eabg5554. [06/28/2021]
Summary:
Space radiation may cause DNA damage to cells and concern for the inheritance of mutations in offspring after deep space exploration. However, there is no way to study the long-term effects of space radiation using biological materials. Here, we developed a method to evaluate the biological effect of space radiation and examined the reproductive potential of mouse freeze-dried spermatozoa stored on the International Space Station (ISS) for the longest period in biological research. The space radiation did not affect sperm DNA or fertility after preservation on ISS, and many genetically normal offspring were obtained without reducing the success rate compared to the ground-preserved control. The results of ground x-ray experiments showed that sperm can be stored for more than 200 years in space. These results suggest that the effect of deep space radiation on mammalian reproduction can be evaluated using spermatozoa, even without being monitored by astronauts in Gateway.
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An easy-to-use function to assess deep space radiation in human brains
Khaksarighiri S, Guo J, Wimmer-Schweingruber R, Narici L. Sci Rep. 2021 Jun 3;11(1):11687. [06/14/2021]
Summary:
Health risks from radiation exposure in space are an important factor for astronauts' safety as they venture on long-duration missions to the Moon or Mars. It is important to assess the radiation level inside the human brain to evaluate the possible hazardous effects on the central nervous system especially during solar energetic particle (SEP) events. We use a realistic model of the head/brain structure and calculate the radiation deposit therein by realistic SEP events, also under various shielding scenarios. We then determine the relation between the radiation dose deposited in different parts of the brain and the properties of the SEP events and obtain some simple and ready-to-use functions which can be used to quickly and reliably forecast the event dose in the brain. Such a novel tool can be used from fast nowcasting of the consequences of SEP events to optimization of shielding systems and other mitigation strategies of astronauts in space.
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The individual and combined effects of spaceflight radiation and microgravity on biologic systems and functional outcomes
Willey JS, Britten RA, Blaber E, Tahimic CGT, Chancellor J, Mortreux M, Sanford LD, Kubik AJ, Delp MD, Mao XW.and published in J Environ Sci Health C Toxicol Carcinog. 2021;39(2):129-179. [05/18/2021]
Summary:
Microgravity and radiation present outside of low earth orbit represent risks to astronaut health and performance during and/or after planned long-duration missions. Most ground-based analogues (e.g., mouse or rat studies) that investigate these risks focus on each individual hazard in isolation. However, astronauts will face these (and other) hazards simultaneously during future missions, and thus understanding the biologic and functional responses of combined hazards are necessary for developing appropriate countermeasures. This review describes the biologic and functional outcomes observed in the skeletal, ocular, cardiovascular, and central nervous systems, and also stem cell responses, after exposure to ground-based microgravity (e.g., tail suspension to impart hind limb unloading and partial weight bearing models) and radiation simulations. In vitro studies and spaceflight data are discussed as appropriate.
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The role of nutrition in space exploration: Implications for sensorimotor, cognition, behavior and the cerebral changes due to the exposure to radiation, altered gravity, and isolation/confinement hazards of spaceflight
Zwart SR, Mulavara AP, Williams TJ, George K, Smith SM. Neurosci Biobehav Rev. 2021 Apr 26;S0149-7634(21)00185-8. Review. [05/12/2021]
Summary:
Accumulated evidence suggests that nutrition has an important role in optimizing cognition and reducing the risk of neurodegenerative diseases caused by neuroinflammation. Here we review the nutritional perspective of how these spaceflight hazards affect the astronaut's brain, behavior, performance, and sensorimotor function. We also assess potential nutrient/nutritional countermeasures that could prevent or mitigate spaceflight risks and ensure that crewmembers remain healthy and perform well during their missions.
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Modeling space radiation induced cognitive dysfunction using targeted and non-targeted effects
Shuryak I, Brenner DJ, Blattnig SR, Shukitt-Hale B, Rabin BM. Sci Rep. 2021 Apr 23;11(1):8845 [04/30/2021]
Summary:
Radiation-induced cognitive dysfunction is increasingly recognized as an important risk for human exploration of distant planets. Mechanistically-motivated mathematical modeling helps to interpret and quantify this phenomenon. Here we considered two general mechanisms of ionizing radiation-induced damage: targeted effects (TE), caused by traversal of cells by ionizing tracks, and non-targeted effects (NTE), caused by responses of other cells to signals released by traversed cells. The results of modeling analysis based on these mechanisms suggest that NTE-based radiation effects on brain function are potentially important for astronaut health and for space mission risk assessments.
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Observations of neutron radiation environment during Odyssey cruise to Mars
M.L. Litvak, I.G. Mitrofanov, A.B. Sanin, B. Bakhtin, D.V. Golovin, C. Zeitlin, Life Sciences in Space Research, 2021, Volume 29, May 2021, Pages 53-62 [04/23/2021]
Summary:
In April 2001, Mars Odyssey spacecraft with the High Energy Neutron Detector (HEND) onboard was launched to Mars. HEND/Odyssey was switched on measurement mode for most of transit to Mars to monitor variations of spacecraft background and solar activity. Although HEND/Odyssey was originally designed to measure Martian neutron albedo and to search for Martian subsurface water/water ice, its measurements during cruise phase to Mars are applicable to evaluate spacecraft ambient radiation background. We have modeled the spacecraft neutron spectral density and compared it with HEND measurements to estimate neutron dose equivalent rates during Odyssey cruise phase, which occurred during the maximum period of solar cycle 23. We find that the Odyssey ambient neutron environment during May - September 2001 yields 10.6 ± 2.0 µSv per day in the energy range from 0 to 15 MeV, and about 29 µSv per day when extrapolated to the 0-1000 MeV energy range during solar quiet time (intervals without Solar Particle Events, SPEs). We have also extrapolated HEND/Odyssey measurements to different periods of solar cycle and find that during solar minimum (maximum of GCR flux), the neutron dose equivalent rate during cruise to Mars could be as high as 52 µSv per day with the same shielding. These values are in good agreement with results reported for a similar measurement made with an instrument aboard the Mars Science Laboratory during its cruise to Mars in 2011-2012.
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Effects of low dose space radiation exposures on the splenic metabolome
Laiakis EC, Shuryak I, Deziel A, Wang YW, Barnette BL, Yu Y, Ullrich RL, Fornace AJ Jr, Emmett MR., Int J Mol Sci. 2021 Mar 17;22(6):3070. [04/20/2021]
Summary:
In this study, we investigated the effects in the overall metabolism of three different low dose radiation exposures (γ-rays, 16O, and 56Fe) in spleens from male C57BL/6 mice at 1, 2, and 4 months after exposure. Forty metabolites were identified with significant enrichment in purine metabolism, tricarboxylic acid cycle, fatty acids, acylcarnitines, and amino acids. Early perturbations were more prominent in the γ irradiated samples, while later responses shifted towards more prominent responses in groups with high energy particle irradiations. Regression analysis showed a positive correlation of the abundance of identified fatty acids with time and a negative association with γ-rays, while the degradation pathway of purines was positively associated with time. Taken together, there is a strong suggestion of mitochondrial implication and the possibility of long-term effects on DNA repair and nucleotide pools following radiation exposure.
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Dose fractionation during puberty is more detrimental to mammary gland development than an equivalent acute dose of radiation exposure
Wiedmeyer B, To J, Sridharan DM, Chien LC, Snijders AM, Mori H, Pluth JM. Int J Radiat Oncol Biol Phys. 2021 Apr 1;109(5):1521-32. [04/11/2021]
Summary:
In this work we have investigated using a mouse model system how two types of radiation dose regimens may differentially impact mammary organ formation during an especially sensitive window in development, puberty. Our data revealed that fractionated radiation exposures produced greater immune and mammary defects as compared to controls and that these effects were more pronounced in the more radiation sensitive, BALB/c mice. Together, these findings suggest that fractionated low dose exposures are potentially more damaging to organ development as compared to an equivalent single acute exposure and that genetic background is an important parameter that can modify the severity of these effects.
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Tumor aggressiveness is independent of radiation quality in murine hepatocellular carcinoma and mammary tumor models
Udho EB, Huebner SM, Albrecht DM, Matkowskyj KA, Clipson L, Hedican CA, Koth R, Snow SM, Eberhardt EL, Miller D, Van Doorn R, Gjyzeli G, Spengler EK, Storts DR, Thamm DH, Edmondson EF, Weil MM, Halberg RB, Bacher JW. in Int J Radiat Biol. 2021 Mar 15;1-35. Online ahead of print. [04/02/2021]
Summary:
The goal of this research is to test whether high-LET HZE radiation induced tumors are more aggressive. Murine models of mammary and liver cancer were used to compare the impact of exposure to 0.2Gy of 300MeV/n silicon ions, 3 Gy of γ-rays or no radiation. For the mammary cancer models, there was no significant change in the tumor latency or metastasis in silicon-irradiated mice compared to controls. For the liver cancer models, we observed an increase in tumor incidence but not tumor aggressiveness in irradiated mice. Thus, enhanced aggressiveness does notappear to be a uniform characteristic of all tumors in HZE-irradiated animals.
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Older Research Citations may be found in the Bibliography.