Chief Editor: Walter Schimmerling, Ph.D.

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 - November 2021

Featured Article

Current Research Citations

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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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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Comparison between PHITS and GEANT4 Simulations of the Heavy Ion Beams at the BEVALAC at LBNL and the Booster Accelerator at BNL
Sungmin Pak, Francis A. Cucinotta, Life Sciences in Space Research,Volume 29,2021,Pages 38-45 [03/24/2021]
Summary:
Heavy charged particles have been discussed for clinical use due to their superior dose-depth distribution compared to conventional radiation such as X-rays. In addition, high-charge and energy (HZE) ions in galactic cosmic rays (GCR) present important health risks for crewed space missions to the Earth's moon or Mars. Experiments at heavy ion accelerators are used in radiobiology studies; however, numerical simulations of track segment or Bragg peak irradiations are complicated by the details of the beam-line and dosimetry systems. The goal of the present work is in support of biophysics modeling of historical radiobiology data at Lawrence Berkeley National Laboratory (LBNL) and more recent results from the Brookhaven National Lab (BNL) facility (NASA Space Radiation Lab (NSRL)). In this work, the Spread-Out Bragg Peak (SOBP) of 4He, 12C, and 20Ne particles, and a Bragg curve of 56Fe ion have been simulated numerically in the geometries of LBNL and BNL using the Monte-Carlo based PHITS and GEANT4 simulation toolkits. The dose contributions of primary particles and secondary particles, including neutrons and photons, in the target material are computed and discussed as well. Comparisons suggest more contributions of secondaries in GEANT4 simulations compared to PHITS simulations, and less statistical fluctuation and better prediction of neutrons in PHITS simulations. Neutrons and gamma-rays are estimated to make minor contributions to absorbed doses for these beams.
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Double-Differential FRaGmentation (DDFRG) models for proton and light ion production in high energy nuclear collisions
J. Norbury. Nuclear Instruments and Methods in Physics Research A, vol. 986, p. 164681, 2021. [03/23/2021]
Summary:
A new set of Double-Differential FRaGmentation (DDFRG) models for proton and light ion production from high energy nucleus-nucleus collisions, relevant to space radiation, is introduced. The proton model employs thermal production from the projectile, central fireball and target sources, as well as quasi-elastic direct knockout production. The light ion model uses a hybrid coalescence model. The data show a prominent quasi-elastic peak at small angles which becomes highly suppressed at large angles. The models are able to describe this wide range of experimental data with only a limited set of model parameters. Closed form analytic formulas for double-differential energy and angle cross-sections as well as single-differential spectral cross-sections are developed. These analytic formulas enable highly efficient computation for radiation transport codes.
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Are Further Cross Section Measurements Necessary for Space Radiation Protection or Ion Therapy Applications? Helium Projectiles
J. Norbury, G. Battistoni, J. Besuglow, L. Bocchini, D. Boscolo, A. Botvina, M. Clowdsley, W. de Wet, M. Durante, M. Giraudo, T. Haberer, L. Heilbronn, F. Horst, M. Krämer, C. La Tessa, F. Luoni, A. Mairani, S. Muraro, R. Norman, V. Patera, G. Santin, C. Schuy, L. Sihver, T. Slaba, N. Sobolevsky, A. Topi, U. Weber, C. Werneth, C. Zeitlin Frontiers in Physics, vol. 8, pp. 1-30, 2020. [03/23/2021]
Summary:
This work reviews the importance of 4He projectiles to space radiation and ion therapy, and outline the present status of neutron and light ion production cross section measurements and modeling, with recommendations for future needs.
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Long-term effects of very low dose particle radiation on gene expression in the heart: Degenerative disease risk
Garikipati VNS, Arakelyan A, Blakely EA, Chang PY, Truongcao MM, Cimini M, Malaredy V, Bajpai A, Addya S, Bisserier M, Brojakowska A, Eskandari A, Khlgatian MK, Hadri L, Fish KM, Kishore R, Goukassian DA Cells. 2021 Feb 13;10(2):387 [03/16/2021]
Summary:
In this study, we provide the transcriptome analysis of mouse hearts exposed to low and very low doses of gamma-IR 137Cs (40-160 cGy), 14Si-IR (4-32 cGy, 260 MeV/n) or 22Ti-IR (3-26 cGy, 1 GeV/n) ion irradiation. Our results show that 16 months after a single low- or very low doses of IR exposure, the gene expression in the heart tissue is significantly differentially regulated compared to the sham-treated, non-irradiated controls, suggesting there are long-term effects on dysregulation of different molecular pathways that are associated with various disease and biological processes. Additionally, our bioinformatics analyses revealed the following: (i) there were no clear lower IR thresholds for HZE- or γ-IR; (ii) there were 12 common differentially expressed genes across all 3 IR types; (iii) these 12 overlapping genes predicted various degrees of cardiovascular, pulmonary, and metabolic diseases, cancer, and aging; and (iv) these 12 genes revealed an exclusive non-linear DEG pattern in 14Si- and 22Ti-IR-exposed hearts, whereas two-thirds of γ-IR-exposed hearts revealed a linear pattern of DEGs.
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Life-long brain compensatory responses to galactic cosmic radiation exposure
Miry O, Zhang XL, Vose LR, Gopaul KR, Subah G, Moncaster JA, Wojnarowicz MW, Fisher AM, Tagge CA, Goldstein LE, Stanton PK. Sci Rep. 2021 Feb 22;11(1):4292.). [03/15/2021]
Summary:
To our knowledge, this study is the first to uncover lifespan-long effects of high-energy heavy particle radiation mimicking exposure to galactic cosmic radiation (GCR), on neurogenesis, synaptic plasticity, and learning and memory in mice. Changes observed 2 months after a single GCR exposure were characterized by reductions in hippocampal neurogenesis, smaller activity-dependent long-term potentiation of synaptic strength (LTP), and impaired spatial, hippocampus-dependent, learning acquisition. Six months after GCR exposure, impairments in learning disappeared, and LTP was actually enhanced. 12-20 months post-GCR exposure, we observed dramatic rebound increases in neurogenesis of newborn neurons in the dentate gyrus, larger LTP, and more rapid learning acquisition in a spatial learning task.
The GCR exposure studied was designed to mimic cumulative exposure levels expected on long-term manned missions to Mars. This lifespan study shows that such exposure can produce complex effects on the brain that are lifelong. The neurophysiological, cognitive and behavioral results of such long-term effects on astronauts is likely to be a complex combination of deficits and compensatory recovery mechanisms with their own unpredictable consequences. These consequences have the potential to affect the success of deep space manned missions, and the intrepid explorers throughout their lives. Deeper studies of the consequences of these long-lasting effects, and a search for ways to ameliorate them, will be a key goal in maximizing mission performance and success.
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On the radiation environment during consecutive balloon flights over New Mexico and Antarctica
Berger Thomas, Matthiä Daniel, Marsalek Karel, Przybyla Bartos, Aeckerlein Joachim, Rohde Markus. Wirtz Michael, Moeller Ralf, James Leandro M. and Lane Michael. Earth and Space Science Open Archive}, 2021 (in review) [03/07/2021]
Summary:
The maximum measured daily dose values over Antarctica reached 202 µGy/day (at RC =0 GV), a level of particular significance for the space exploration community, considering we have observed similar dose values (212 µGy/day) on the surface of Mars across equivalent time periods, as measured by the Curiosity rover (Berger et al., 2020). Short of sending experiments or instruments to the Red Planet, or as a progressive stepping stone for eventually journeying into deep space, our results support the idea that long duration Antarctic balloon missions can be used for accurately introducing experiments or instruments to sustained Mars-like radiation conditions.
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The effect of helium ion radiation on the material properties of bone
Thomas PK, Sullivan LK, Dickinson GH, Davis CM, Lau AG. Calcif Tissue Int. 2021 Jan 30. Online ahead of print. [02/24/2021]
Summary:
Ionizing radiation is known to affect bone health. This study investigated the effects of helium ion radiation exposure on the material properties of bone. Rats were exposed to 0, 5, or 25 cGy doses of helium-4 radiation and evaluated at 7, 30, 90, and 180 day time points after radiation exposure. The shear modulus of the femur cortical bone was investigated using spherical micro-indentation.
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Impact of galactic cosmic ray simulation on nutritional content of foods
Douglas GL, Cooper MR, Wu H, Gaza R, Guida P, Young M. Life Sci Space Res. 2021 Feb;28:22-5. [01/31/2021]
Summary:
Foods packaged for future deep-space exploration missions may be prepositioned ahead of astronaut arrival and will be exposed to galactic cosmic rays (GCRs) and solar radiation in deep space at higher levels and different spectrums than those found in low-Earth orbit (LEO). In this study, we have evaluated the impact of a GCR simulation (approximately 0.5 and 5 Gy doses) at the NASA Space Radiation Laboratory (NSRL) on two retort thermostabilized food products that are good sources of radiation labile nutrients (thiamin, vitamin E, or unsaturated fats). No trends or nutritional differences were found between the radiation-treated samples and the control immediately after treatment or one-year after treatment. Small changes in a few nutrients were measured following one-year of storage. Further studies may be needed to confirm these results, as the foods in this study were heterogeneous, and this may have masked meaningful changes due to pouch-to-pouch variations.
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Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation
Oizumi T, Ohno R, Yamabe S, Funayama T, Nakamura AJ. Life (Basel). 2020 Dec 10;10(12):341. doi: 10.3390/life10120341. PMID: 33321941; PMCID: PMC7763067 [01/31/2021]
Summary:
In this study, normal human fibroblasts were irradiated with proton, helium, or carbon ion beams. Immunostaining for γ-H2AX and 53BP1 was performed over time to evaluate the kinetics of DNA damage repair. Our data clearly show that the repair kinetics of DNA double strand breaks (DSBs) induced by carbon ion irradiation, which has a high linear energy transfer (LET), are significantly slower than those of proton and helium ion irradiation. Mixed irradiation with carbon ions, followed by helium ions, did not have an additive effect on the DSB repair kinetics. Interestingly, the mean γ-H2AX focus size was shown to increase with LET, suggesting that the delay in repair kinetics was due to damage that is more complex. Further, the 53BP1 focus size also increased in an LET-dependent manner. Repair of DSBs, characterized by large 53BP1 foci, was a slow process within the biphasic kinetics of DSB repair, suggesting non-homologous end joining with error-prone end resection. Our data suggest that the biological effects of space radiation may be significantly influenced by the dose as well as the type of radiation exposure.
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Predicting the Radiation Sensitivity of Male and Female Rhesus Macaques Using Gene Expression
P. Ostheim, M. Majewski, Z. Gluzman-Poltorak, V. Vainstein, L. A. Basile, A. Lamkowski, S. Schüle, H. L. Kaatsch, M. Haimerl, C. Stroszczynski, M. Port, and M. Abend Radiation Research 195(1), 25-37, (12 November 2020) [01/18/2021]
Summary:
Radiosensitivity differs in humans and likely among closely-related primates. Reasons for variation in radiosensitivity are not well known. We examined preirradiation gene expression in peripheral blood among male and female rhesus macaques (n=142) which did or did not survive (up to 60 days) after whole-body irradiation with 700 cGy (LD66/60). We evaluated gene expression in a two-phase study design where phase I was a whole genome screen [next generation sequencing (NGS)] for mRNAs (RNA-seq). Differential gene expression (DGE) was defined as a statistically significant and 2-fold up- or downregulation of mRNA species and was calculated between groups of survivors and non-survivors (reference) and by gender. Altogether 659 genes were identified, but the overlapping number of differentially expressed genes (DGE) observed in both genders was small (n = 36). Fifty-eight candidate mRNAs were chosen for independent validation in phase II using qRT-PCR. Among the 58 candidates, 16 were of significance or borderline significance (t test) by DGE. Univariate and multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis further refined and identified the most outstanding validated genes and gene combinations. The combination of EPX with SLC22A4 (P = 0.03, ROC=0.85) appeared most predictive for the clinical outcome of male macaque groups and MBOAT4 (P = 0.0004, ROC = 0.81) was most predictive for females.
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Inflammation mediates the development of aggressive breast cancer following radiotherapy
Ma L, Gonzalez-Junca A, Zheng Y, Ouyang H, Illa-Bochaca I, Horst KC, Krings G, Wang Y, Fernandez-Garcia I, Chou W, Barcellos-Hoff MH. in Clin Cancer Res. 2021 Jan 5. Online ahead of print. [01/15/2021]
Summary:
The mechanisms by which radiation increases cancer risk include targeted effects in the irradiated cell, like mutation, and non-targeted effects that signal among cells in response to damage. The research reported by Ma et al. evaluates the contribution of targeted versus non-targeted radiation effects to the development of breast cancer. In women treated with radiation for early cancer, breast cancer risk is significantly elevated, but more importantly, radiation-preceded breast cancer is a more aggressive disease. Ma et al. analyzed the composition of breast cancers arising in women who treated for Hodgkin's lymphoma and used a series of genetic-chimera mouse experiments to examine how a single, low dose radiation exposure altered mammary carcinogenesis. They show that the tumor microenvironment of radiation-preceded breast cancer was markedly immunosuppressive compared to that of age-matched sporadic breast cancer as evidenced by high levels of cyclooxygenase-2 and transforming growth factor-beta and low lymphocytic infiltrate. Mouse tumors arising after irradiation were also characterized by an immunosuppressive microenvironment. A series of experiments showed that this feature of radiation-preceded breast cancers occurred even when the epithelium was not irradiated and in the absence of adaptive immunity. However, the immunosuppressive features were eliminated by administration of a short course of aspirin after irradiation to reduce low-level inflammation. These studies support anti-inflammatory treatments as a means to reduce aggressive cancers that occur after radiation exposure.
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Microglia depletion and cognitive functions after brain injury: From trauma to galactic cosmic ray
Paladini MS, Feng X, Krukowski K, Rosi S. Neurosci Lett. 2020 Nov 28. [Epub ahead of print] Review. [12/31/2020]
Summary:
Microglia are the resident immune cells of the central nervous system. Insults such as traumatic brain injury, therapeutic brain irradiation and galactic cosmic ray exposure are associated with maladaptive chronic microglia activation. Chronic microglia activation contributes to injury-related impairments in cognitive functions. Microglia depletion represents a useful tool for more extensive investigations of microglia roles, but also a potential therapeutic approach to ameliorate or prevent cognitive dysfunctions following brain injury.
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Multiple sensory illusions are evoked during the course of proton therapy
Narici L, Titova E, Obenaus A, Wroe A, Loredo L, Schulte R, Slater JD, Nelson GA. Life Sci Space Res. 2020 Aug;26:140-8. [12/21/2020]
Summary:
The effects of radiation on sensory physiological responses have been reported in astronauts and in patients undergoing radiotherapy. A retrospective study in a cohort of proton radiotherapy patients found conscious reporting of sensory illusions in visual, olfactory auditory and gustatory senses. Further, brain regions receiving the highest proton doses corresponded to the sensory anatomical structures. This study suggests that prospective studies interrogating illusions from all sensory modalities are warranted and could contribute to radiation risk assessments for space exploration and for radiotherapy patients.
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Can a comparison of clinical and deep space irradiation scenarios shed light on the radiation response of the brain?
C. Limoli, Br J Radiol. 2020 Nov 1;93(1115):20200245. [12/20/2020]
Summary:
The purpose of this article was to draw comparisons between two very different and distinct radiation exposure scenarios, and to discern whether any similarities between clinical brain tumor treatments and space radiation exposure could help in the assessment of clinical outcomes and/or risk mitigation following deep space travel.
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DNA damage baseline predicts resilience to space radiation and radiotherapy
Pariset E, Bertucci A, Petay M, Malkani S, Lopez Macha A, Paulino Lima IG, Gomez Gonzalez V, Tin AS, Tang J, Plante I, Cekanaviciute E, Vazquez M, Costes SV. Cell Rep. 2020 Nov 21:108434. [Epub ahead of print] [12/15/2020]
Summary:
In this work we measure genotoxic stress in humans by quantifying the amount of DNA double-strand breaks (DSBs) in immune cells in vivofrom a simple finger prick and ex-vivo using a blood draw. We first showed in 674 healthy donors that the endogenous level of DSBs increases with age and with latent cytomegalovirus infection. Two smaller cohorts were analyzed for DSB induction and repair by exposing lymphocytes ex-vivo to either galactic cosmic ray components or protons/gamma rays under a radiotherapy protocol. Our work suggests low baseline DSB is a potential biomarker for health resilience in space as indicated by fewer clinical complications for radiotherapy patients, and enhanced DNA damage repair and cytokine responses for healthy donors.
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Sex-specific cognitive deficits following space radiation exposure
Parihar VK, Angulo MC, Allen BD, Syage A, Usmani MT, Passerat de la Chapelle E, Amin AN, Flores L, Lin X, Giedzinski E, Limoli CL Front Behav Neurosci. 2020 Sep 16;14:535885 [12/02/2020]
Summary:
Data included in this manuscript indicate that fundamental differences in inflammatory cascades between male and female mice may drive divergent CNS radiation responses that differentially impact the structural plasticity of neurons and neurocognitive outcomes following cosmic radiation exposure.
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53P1 Repair Kinetics for Prediction of In Vivo Radiation Susceptibility in 15 Mouse Strains
Eloise Pariset, Sébastien Penninckx, Charlotte Degorre Kerbaul, Elodie Guiet, Alejandra Lopez Macha, Egle Cekanaviciute, Antoine M. Snijders, Jian-Hua Mao, François Paris, Sylvain V. Costes Radiation Research, 194(5), 485-499, (29 September 2020) [12/01/2020]
Summary:
This report introduces a novel mathematical formalism to predict the kinetics of DNA damage repair after exposure to X-rays and space radiation components, with potential applications in radiotherapy and human space exploration. Our method is based on monitoring DNA damage repair protein 53BP1 that forms radiation-induced foci (RIF) at locations of DNA double-strand breaks (DSB) in the nucleus and comparing its expression in primary skin fibroblasts isolated from 15 different mice strains. We show that genetics is a key factor in individual speed and the efficiency of DNA damage repair. We further link kinetics metrics to in vivo phenotypes in these strains, illustrating such metrics as potential surrogate biomarkers for in vivo radiation toxicity, specifically survival levels of immune cells in irradiated mice and spontaneous cancer incidence. This study is part of a series of manuscripts published in Radiation Research that reports clustering of nearby DSB into single repair units in the same mouse fibroblasts [https://pubmed.ncbi.nlm.nih.gov/31081741/] and optimizes 53BP1 foci detection based on cell proliferation levels [https://meridian.allenpress.com/radiation-research/article-abstract/doi/10.1667/RADE-20-00165.1/447610/Considering-Cell-Proliferation-to-Optimize?redirectedFrom=fulltext]. In addition, our group showed that monitoring 53BP1 foci levels can be used to predict radiation sensitivity, not only in mouse fibroblasts but also in human immune cells [https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31423-6], with correlations between the level of spontaneous foci and secondary effects to radiotherapy in 30 prostate cancer patients, as well as ex vivo responses to space radiation components in 300+ healthy donors. Genetic Wide Association studies in both these 15 strains of mice and our cohort of 800+ patients is ongoing in the Radiation Biophysics Laboratory at NASA Ames Research Center.
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Updated deterministic radiation transport for future deep space missions
Slaba TC, Wilson JW, Werneth CM, Whitman K. Life Sci Space Res. 2020 Nov;27:6-18. [11/30/2020]
Summary:
NASA's deterministic transport code HZETRN, and its three-dimensional (3D) counterpart, 3DHZETRN, are being used to characterize the space radiation environment over a wide range of scenarios, including future planned missions to the moon or Mars. Combined with available spaceflight measurements, these tools provide the fundamental input for biological risk projection models used to verify astronaut safety and satisfy agency limits in support of exploration initiatives. In this work, significant updates to the deterministic radiation transport models are presented. Charged muons and pions are fully coupled to neutron and light ion (Z < 2) transport solutions in 1D and 3D. A direct comparison of deterministic and Monte Carlo transport methodologies using the same nuclear interaction databases is also provided. It is shown that Geant4 and 3DHZETRN are in excellent agreement when the same cross sections are used. The deterministic codes are also compared to ISS data, and it is found that the updated 3D procedures are within measurement uncertainty (+5%) at cutoff rigidities below 1 GV, which approaches free space conditions.
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Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions
Li Z, Jella KK, Jaafar L, Moreno CS, Dynan WS. Life Sci Space Res. 2020 Nov 5. [Article in Press] [11/15/2020]
Summary:
Exposure of human bronchial epithelial cells to energetic heavy ions, representative of species found in galactic cosmic rays, stimulates exosome release. Preparations enriched for these nanometer-scale extracellular vesicles contain pro-inflammatory damage-associated molecular patterns, together with a variety of microRNAs (miRNAs). The miRNA profile is skewed toward a small number of species involved in cancer initiation and progression, consistent with a role in mediating non-targeted radiation effects.
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Heavy ion space radiation triggers ongoing DNA base damage by downregulating DNA repair pathway
Suman S, Jaruga P, Dizdaroglu M, Fornace AJ Jr, Datta K. Life Sci Space Res. 2020 Nov 27:27-32. [10/28/2020]
Summary:
Persistent sub-lethal oxidative stress and ongoing DNA damage have been attributed to the enhanced risk of gastrointestinal (GI) carcinogenesis after ionizing radiation (IR) exposure. IR-induced oxidative stress is known to cause a myriad of oxidative DNA damages to DNA bases and the sugar moiety, while base excision repair (BER) and nucleotide excision repair (NER) mechanisms are predominantly involved in removing these oxidative DNA lesions. In our earlier studies, we demonstrated that exposure to 56Fe-ion caused persistent oxidative stress in intestinal epithelial cells (IECs), so the purpose of the recent study was to detect and quantify oxidative DNA-lesions and respective repair pathways in the mouse intestine. Gas chromatography/tandem mass spectrometry (GC-MS/MS) was used to detect and quantify oxidative DNA damage, while qPCR and western-blot analysis was done to assess alterations in BER and NER pathways in ? and 56Fe-exposed mouse intestine. Exposure to 56Fe-ion resulted in significantly higher levels of oxidative DNA base lesions relative to control and ? exposed animals. Assessment of BER and NER also showed greater downregulation of pathway factors at both mRNA and protein levels after 56Fe-ion exposure. These results clearly indicate that downregulation of the BER and NER pathways can contribute to ongoing DNA base damages a long time after radiation exposure and has implications for GI-carcinogenesis after energetic heavy ion (HZE) exposure during space travel.
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Spaceflight medical countermeasures: A strategic approach for mitigating effects from solar particle events
Lisa Cantrell, Int J Radiat Biol. 2020 Sep 18. [10/18/2020]
Summary:
NASA was recently charged with returning humans to the lunar surface within the next five years. This will require preparation for spaceflight missions of longer distance and duration than ever performed in the past. Protecting the crew and mission from the hazards associated with spaceflight will be a priority, particularly space radiation. Physical shielding, space weather monitoring, and more recently storm shelters are all possible means of protecting crew during a SPE. This paper discusses the mitigation strategies in the event of a SPE that can be implemented for Artemis missions and identifies numerous areas of research for future improvements.
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Practicalities of dose management for Japanese astronauts staying at the International Space Station
T Komiyama, Ann ICRP. 2020 Sep 24. [10/11/2020]
Summary:
Japanese astronauts started staying at the International Space Station (ISS) in 2009, with each stay lasting for approximately 6 months. In total, seven Japanese astronauts have stayed at the ISS eight times. As there is no law for protection against space radiation exposure of astronauts in Japan, the Japan Aerospace Exploration Agency (JAXA) created its own rules and has applied them successfully to radiation exposure management for Japanese ISS astronauts, collaborating with ISS international partners. Regarding dose management, JAXA has implemented several dose limits to protect against both the stochastic effects of radiation and dose-dependent tissue reactions. The scope of the rules includes limiting exposure during spaceflight, exposure during several types of training, and exposure from astronaut-specific medical examinations. We, therefore, are tasked with calculating the dose from all exposure types applied to the dose limits annually for each astronaut. Whenever a Japanese astronaut is at the ISS, we monitor readings of an instrument in real-time to confirm that the exposed dose is below the set limits, as the space radiation environment can fluctuate in relation to solar activity.
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Radiation dose and its protection in the moon from galactic cosmic rays and solar energetic particles: At the lunar surface and in a lava tube
Naito M, Hasebe N, Shikishima M, Amano, Y, Haruyama J, Matias-Lopes JA, Kim KJ, Kodaira S. J Radiol Prot. 2020 Sep 23;40(4):947-61. [10/11/2020]
Summary:
Radiation environment at the lunar surface and in a lunar vertical hole with a horizontal lava tube was estimated. The effective dose equivalent due to galactic cosmic ray (GCR) particles at the lunar surface reached 416 mSv/year at most, and that due to solar energetic particles reached 2190 mSv. On the other hand, the vertical hole of the lava tube provides significant radiation protection. The exposure by GCR particles at the bottom of the vertical hole was found to be below 30 mSv/year while inside the horizontal lava tube, the value was less than 1 mSv/year, which corresponds to the reference values for human exposure on the Earth. We expect that the lunar holes will be useful components in the practical design of a lunar base to reduce radiation risk and to expand mission terms.
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Response to comments by Bevelacqua and Mortazavi
Rabin BM, Cahoon DS, Shukitt-Hale B.Sci Space Res. 2020 Nov;27:111-2. Epub 2020 Sep 23 [10/11/2020]
Summary:

The main thrust of the comments by Bevelacqua and Mortazavi (2020) about the paper by Cahoon et al. (2020) is that we ignored the potential adaptive responses resulting from low level exposure to radiation, a phenomenon known as "radiation hormesis". The adaptive response produced by preexposure to a low dose of radiation is considered a non-targeted effect of ionizing radiation. While we did show a non-targeted effect on brain function following exposure of the body only, we did not raise the issue of an adaptive response to radiation in our paper because our experimental design, using only a single exposure, did not allow an evaluation of the possible effects of preexposure on the production of neurochemical changes in the brain and the concomitant disruption of cognitive performance. Because the experiment was not designed to evaluate possible adaptive effects of preexposure to a low dose of radiation, we do not think that their comments are relevant.
Bevelacqua, J.J., Mortazavi, S.M.J., 2020. Comments on "Effects of partial- or whole-body exposures to 56Fe particles on brain function and cognitive performance in rats". Life Sci. Space Res.
Cahoon, D.S., Shukitt-Hale, B., Bielinski, D.F., Hawkins, E.M., Cacioppo, A.M., Rabin, B.M., 2020. Effects of partial- or whole-body exposures to 56Fe particles on brain function and cognitive performance in rats. Life Sci. Space Res. 27, 56-63.


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Older Research Citations may be found in the Bibliography.