Looking on the horizon; potential and unique approaches to developing radiation countermeasures for deep space travel

Bokhari, Rihana; Beheshti, Afshin; Blutt, Sarah E.; Bowles, Dawn E.; Brenner, David; Britton, Robert A.; Bronk, Lawrence F.; Cao, Xu; Chatterjee, Anushree; Clay, Delisa E; Courtney, Colleen M.; Fox, Donald T.; Gaber, M. Waleed; Gerecht, Sharon; Grabham, Peter; Grosshans, David R.; Guan, Fada; Jezuit, Erin A.; Kirsch, David G.; Liu, Zhandong; Maletić-Savatić, Mirjana; Miller, Kyle M.; Montague, Ruth A.; Nagpal, Prashant; Osenberg, Sivan; Parkitny, Luke; Pierce, Niles A.; Porada, Christopher D.; Rosenberg, Susan M.; Sargunas, Paul R; Sharma, Sadhana; Spangler, Jamie B.; Tavakol, Daniel Naveed; Thomas, Dilip; Vunjak‐Novakovic, Gordana; Wang, Chunbo; Whitcomb, Luke; Young, Damian W.; Donoviel, Dorit B.

doi:10.1016/j.lssr.2022.08.003

Cited by 5 publications

(2 citation statements)

References 82 publications

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“…[1][2][3][4][5][6][7][8] Ionizing radiation influences several aspects of everyday life due to natural radiation background (cosmic and terrestrial sources), medical intervention (imaging and therapy), and space exploration (astronauts' missions and space tourism). 9 Thus, it is important to achieve a better understanding of the fundamental mechanisms that are initiated by the interaction of radiation with living organisms.…”

Section: Introductionmentioning

confidence: 99%

Simulation of DNA damage using Geant4‐DNA: an overview of the “molecularDNA” example application

Chatzipapas

Tran

Dordevic³

et al. 2023

Precision Radiation Oncology

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Purpose:The scientific community shows great interest in the study of DNA damage induction, DNA damage repair, and the biological effects on cells and cellular systems after exposure to ionizing radiation. Several in silico methods have been proposed so far to study these mechanisms using Monte Carlo simulations. This study outlines a Geant4-DNA example application, named "molecularDNA", publicly released in the 11.1 version of Geant4 (December 2022).Methods: It was developed for novice Geant4 users and requires only a basic understanding of scripting languages to get started. The example includes two different DNA-scale geometries of biological targets, namely "cylinders" and "human cell". This public version is based on a previous prototype and includes new features, such as: the adoption of a new approach for the modeling of the chemical stage, the use of the standard DNA damage format to describe radiation-induced DNA damage, and upgraded computational tools to estimate DNA damage response.Results: Simulation data in terms of single-strand break and double-strand break yields were produced using each of the available geometries. The results were compared with the literature, to validate the example, producing less than 5% difference in all cases.Conclusion: "molecularDNA" is a prototype tool that can be applied in a wide variety of radiobiology studies, providing the scientific community with an open-access base for DNA damage quantification calculations. New DNA and cell geometries for the "molecularDNA" example will be included in future versions of Geant4-DNA.

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Section: Introductionmentioning

confidence: 99%

Simulation of DNA damage using Geant4‐DNA: an overview of the “molecularDNA” example application

Chatzipapas

Tran

Dordevic³

et al. 2023

Precision Radiation Oncology

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“…Long-duration spaceflight can result in the accumulation of IR exposures that may reach or exceed NASA career exposure limits (600 mSv weighted dose equivalent)—potentially producing both short- and long-term deleterious effects on human physiological systems that may limit mission success and increase risks of central nervous system (CNS) disruption, cardiovascular disease (CVD), and cancer morbidity/mortality in astronauts ( Cucinotta et al, 2001 ; Townsend, 2005 ; Cucinotta and Durante, 2006 ; Durante and Cucinotta, 2008 ; Rodman et al, 2017 ; Almeida-Porada et al, 2018 ; Onorato et al, 2020 ; Simonsen et al, 2020 ). Physical, biological, and pharmacological-based radiation protection and mitigation strategies will be required to ensure successful mission outcomes, complete with charged particle-specific radiation medical countermeasures (MCMs) that are easily administered, can safely be stored long-term and maintain efficacy, and show beneficial effects in multiple radiosensitive tissue compartments, e.g., the bone marrow (BM) niche and gastrointestinal (GI) tract ( Bokhari et al, 2022 ; DiCarlo et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Immediate effects of acute Mars mission equivalent doses of SEP and GCR radiation on the murine gastrointestinal system-protective effects of curcumin-loaded nanolipoprotein particles (cNLPs)

Díaz

Kuhlman

Edenhoffer

et al. 2023

Front. Astron. Space Sci.

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Introduction: Missions beyond low Earth orbit (LEO) will expose astronauts to ionizing radiation (IR) in the form of solar energetic particles (SEP) and galactic cosmic rays (GCR) including high atomic number and energy (HZE) nuclei. The gastrointestinal (GI) system is documented to be highly radiosensitive with even relatively low dose IR exposures capable of inducing mucosal lesions and disrupting epithelial barrier function. IR is also an established risk factor for colorectal cancer (CRC) with several studies examining long-term GI effects of SEP/GCR exposure using tumor-prone APC mouse models. Studies of acute short-term effects of modeled space radiation exposures in wildtype mouse models are more limited and necessary to better define charged particle- induced GI pathologies and test novel medical countermeasures (MCMs) to promote astronaut safety.Methods: In this study, we performed ground-based studies where male and female C57BL/6J mice were exposed to γ-rays, 50 MeV protons, or 1 GeV/n Fe-56 ions at the NASA Space Radiation Laboratory (NSRL) with histology and immunohistochemistry endpoints measured in the first 24 h post-irradiation to define immediate SEP/GCR-induced GI alterations.Results: Our data show that unlike matched γ-ray controls, acute exposures to protons and iron ions disrupts intestinal function and induces mucosal lesions, vascular congestion, epithelial barrier breakdown, and marked enlargement of mucosa-associated lymphoid tissue. We also measured kinetics of DNA double-strand break (DSB) repair using gamma-H2AX- specific antibodies and apoptosis via TUNEL labeling, noting the induction and disappearance of extranuclear cytoplasmic DNA marked by gamma-H2AX only in the charged particle-irradiated samples. We show that 18 h pre-treatment with curcumin-loaded nanolipoprotein particles (cNLPs) delivered via IV injection reduces DSB-associated foci levels and apoptosis and restore crypt villi lengths.Discussion: These data improve our understanding of physiological alterations in the GI tract immediately following exposures to modeled space radiations and demonstrates effectiveness of a promising space radiation MCM.

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Compact portable sources of high-LET radiation: Validation and potential application for galactic cosmic radiation countermeasure discovery

Hertel

Biegalski

Nelson

et al. 2022

Life Sciences in Space Research

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Looking on the horizon; potential and unique approaches to developing radiation countermeasures for deep space travel

Cited by 5 publications

References 82 publications

Simulation of DNA damage using Geant4‐DNA: an overview of the “molecularDNA” example application

Simulation of DNA damage using Geant4‐DNA: an overview of the “molecularDNA” example application

Immediate effects of acute Mars mission equivalent doses of SEP and GCR radiation on the murine gastrointestinal system-protective effects of curcumin-loaded nanolipoprotein particles (cNLPs)

Compact portable sources of high-LET radiation: Validation and potential application for galactic cosmic radiation countermeasure discovery

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