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Project Title:  Space Radiation Risk Assessment Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 06/01/2006  
End Date: 08/30/2013  
Task Last Updated: 08/01/2011 
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Principal Investigator/Affiliation:   Cucinotta, Francis A Ph.D. / University of Nevada, Las Vegas 
Address:  Health Physics & Diagnostic Sciences / BHS-345 
4505 Maryland Parkway 
Las Vegas , NV 89154-3037 
Email: not available 
Phone: (702) 895-4320  
Congressional District:
Web:  
Organization Type: NASA CENTER 
Organization Name: University of Nevada, Las Vegas 
Joint Agency:  
Comments: Formerly at NASA Johnson Space Center, until summer 2013 (Ed., Oct 2013) 
Co-Investigator(s)
Affiliation: 
Pluth, Janice  Lawrence Berkeley National Laboratory 
Cornforth, Michael  U TX Medical Branch 
Ponomarev, Artem  Universities Space Research Association 
Kim, Myung-Hee  Universities Space Research Association 
Carra, Claudio  Universities Space Research Association Division of Life Sciences 
Li, Yongfeng  Universities Space Research Association 
Key Personnel Changes / Previous PI: December 2009 report: Dr. Deepa Sridharan joined the project as a Post-doc at LBNL (Lawrence Berkeley National Laboratory). Dr Zarana Patel left the project from USRA (Universities Space Research Association) in Houston.
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) ARS:Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs)
(2) Cancer:Risk of Radiation Carcinogenesis
(3) CNS:Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure (IRP Rev G)
(4) Degen:Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure (IRP Rev F)
Human Research Program Gaps: (1) Acute02:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict acute radiation risks in astronauts? How can human epidemiology data best support these procedures or models?
(2) Acute06:What are the most effective shielding approaches to mitigate acute radiation risks, how do we know, and implement?
(3) Acute08:How can Probabilistic risk assessment be applied to SPE risk evaluations for EVA, and combined EVA+IVA exposures?
(4) Cancer03:How can experimental models of carcinogenesis be applied to reduce the uncertainties in radiation quality effects from SPEs and GCR, including effects on tumor spectrum, burden, latency and progression (e.g., tumor aggression and metastatic potential)? (IRP Rev F)
(5) Cancer04:How can models of cancer risk be applied to reduce the uncertainties in dose-rate dependence of risks from SPEs and GCR?
(6) Cancer05:How can models of cancer risk be applied to reduce the uncertainties in individual radiation sensitivity including genetic and epigenetic factors from SPE and GCR?
(7) Cancer06:How can models of cancer risk be applied to reduce the uncertainties in the age and gender dependence of cancer risks from SPEs and GCR?
(8) Cancer07:How can systems biology approaches be used to integrate research on the molecular, cellular, and tissue mechanisms of radiation damage to improve the prediction of the risk of cancer and to evaluate the effectiveness of CMs? How can epidemiology data and scaling factors support this approach?
(9) Cancer11:What are the most effective shielding approaches to mitigate cancer risks?
(10) Cancer12:What quantitative models, numerical methods, and experimental data are needed to accurately describe the primary space radiation environment and transport through spacecraft materials and tissue to evaluate dose composition in critical organs for mission relevant radiation environments (ISS, Free-space, Lunar, or Mars)? (IRP Rev F)
(11) CBS-CNS-5:How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE? (IRP Rev F)
(12) CNS06:How can new knowledge and data from molecular, cellular, tissue and animal models of late CNS risks or clinical human data be used to estimate late CNS risks to astronauts from GCR and SPE?
(13) Degen05:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict degenerative tissue risks in astronauts? How can human epidemiology data best support these procedures or models?
Flight Assignment/Project Notes: NOTE: End date changed to 8/30/2013 as PI retired then, per S. Monk/NASA Langley Research Center (Ed., 2/9/15)

Task Description: The Risk Assessment Project at Johnson Space Center is responsible for the integration of results from NASA space radiobiology research into computational models used for astronaut radiation risk assessments. The purpose of the Project is fourfold: (1) evaluate the extent to which ongoing research leads to reduction in the uncertainty of risk assessments and provide, as a metric of program progress, the number of days in space during which the radiation exposure of astronauts remains below NASA limits within a 95% confidence interval (“safe days in space”); (2) perform mission planning studies to predict the number of safe days for any mission; (3) assess the radiation risk to astronauts for ongoing missions in real time; and, (4) provide recommendations for research directions most likely to reduce risk or improve the accuracy of risk predictions.

The four categories of risks from radiation in space are defined by the NASA Bioastronautics Roadmap (BR). They are: 1) Carcinogenesis, 2) Acute and late effects to the Central Nervous System (CNS), 3) Degenerative Tissue Effects such as heart disease and cataracts, and 4) Acute Radiation risks. The number of safe days currently predicted for an astronaut’s career is less than required by mission planning, due to the large uncertainties in risk prediction. In particular, a projection uncertainty below + or - 50% is the goal for the 1000-day Mars mission because the high level of risk will require high precision risk evaluations. The current approach used to project risk is based on epidemiology data and on phenomenological models used to derive risk prediction from them. This approach cannot lead to improvements in the accuracy of risk prediction beyond a factor of approximately 2. New approaches using molecular biology and genetics are the only viable ones for achieving the level of accuracy required by space exploration and a robust program to obtain the required data is supported by the Space Radiation Program. However, how to incorporate these data into risk prediction and assessment models is not well understood. This Project Plan describes the approaches that will be used to develop models of risk assessment based on mechanistic space radiobiology research funded by the Space Radiation Program, leading to incremental uncertainty reduction based on new experimental data, and to the development of application software to be used in the NASA operational radiation protection program. To accomplish these goals, we will establish new molecular based models of risk. The molecular pathways that are the hallmarks of genomic instability and cancer, and the perturbation of these pathways by radiation will be described using systems biology approaches and Monte-Carlo simulation. We will develop descriptive models of such pathways utilizing track structure models of biomolecular damage, and deterministic and stochastic kinetic models of dominant molecular pathways causative of BR radiation risks. These simulations will make maximum use of results from mechanistic space radiobiology, and will replace traditional hazard functions and their inherent uncertainties due to reliance on epidemiological or phenomenological approaches.

Research Impact/Earth Benefits: Radiobiology research provides many important qualitative descriptions of biological effects of radiation on biomolecules, cells, and tissues. The Space Radiation Risk Assessment Project provides an important link that integrates qualitative experimental observations into detailed quantitative biophysical models of radiations risks. This research benefits all humans that will be exposed to ionizing radiation and supports the development of disease models in general.

Models of cancer, CNS, heart disease, acute and other risks developed by the Space Radiation Risk Assessment Project provide NASA with the ability to project risks and develop cost-effective mitigation approaches for future exploration missions.

Our recent focus is the confounding role of tobacco on cancer and circulatory disease risk estimates. Understanding the effects of tobacco usage on radiation risk estimates benefits ground based use of diagnostic procedures that utilize radiation.

Task Progress & Bibliography Information FY2011 
Task Progress: Project A: Integration and Review: A review of current knowledge from space radiation physics was accepted for publication in Reviews of Modern Physics (Durante and Cucinotta, 2011). Several Graphical Users Interface’s (GUI) of risk assessment models and computational tools were developed and published including: a) ARRBOD (Acute Radiation Risk and BRYTNRN Organ Dose); b) NSCR (NASA Space Cancer Risk) c) GERMCode (Galactic Cosmic Radiation, GCR, Event-based Risk Model); d) RITracks (Relativistic Ion Track Structure). The GERMcode was developed to accurately describe fragmentation in the NASA Space Radiation Laboratory (NSRL) beam-line and biological samples, and basic radiobiology experiments.

Project B: Cancer Risk Projection Model and Uncertainties: New findings and knowledge from NSRL and other sources were used to revise the NASA’s risk model for space radiation cancer risks:

1) Revised values for low LET risk coefficients for tissue specific cancer incidence.

2) An analysis of lung cancer and other smoking attributable cancer risks for never-smokers show significantly reduced lung cancer risks as well as overall cancer risks for astronauts as compared to the risk estimated for the average U.S. population.

3) Derivation of track structure based radiation quality functions that depend on charge number, Z, and kinetic energy, E, in place of a dependence on LET alone. The assignment of a smaller maximum in the quality function for leukemia than for solid cancers.

4) Revised uncertainty assessments for all model coefficients in the risk model (physics, low LET risk coefficients, dose and dose-rate effectiveness factor (DDREF), and quality factors), and an alternative uncertainty assessment that considers deviation from linear responses due to non-targeted effects (NTE).

Results of calculations for the average U.S. population show more restrictive dose limits for astronauts above age 40 y as compared to National Council on Radiation Protection and Measurements (NCRP) Report 132, and a modest narrowing of uncertainties if NTEs are not included and much broader uncertainties with NTEs. Risks for never-smokers compared to the average U.S. population are estimated in a mixture model to be reduced by more than 20% and 30% for males and females, respectively. A larger reduction is possible if purely multiplicative risk transfer is assumed.

Project C: Biochemical Kinetics Models of Molecular Pathways: A system biology model (Cucinotta et al., 2008) of the non-homologous end joining (NHEJ) pathway was developed and used to make quantitative descriptions of the gamma H2AX foci and double strand break (DSB) rejoining experiments. The model is extended to consider the radiation quality dependence of the relative fraction of simple and complex DSB, rejoining and associated repair defects, and the kinetics of various radiation induced foci (RIF). In further work, the addition of ataxia telangiectasia mutated (ATM) and the MRN complex to the model was achieved and the role of processing damaged ends by the Artemis proteins is being modeled (Li and Cucinotta, 2011). The interaction of several growth factors with NHEJ components was studied, including the interaction of the growth factors EGFR, IGF1, and TGFbeta-Smad with ATM and DNA-PK. New approaches to Green’s functions for stochastic treatment of molecular diffusion processes were developed (Plante et al. 2011). Flow cytometry or immune-staining considers signals in individual cells and thus provides several unique capabilities to support computation modeling using stochastic approaches. In contrast, methods that average the values of many cells such as Western blots, gene arrays, etc. are limited in elucidating events at low dose where fluctuations are expected to be important. To improve our understanding of DNA repair complexes numerical approaches to simulate immunohistochemistry (Ponomarev et al., 2008, 2009) and flow cytometry experiments (Cucinotta , in preparation, Chappell et al., 2010) were developed. These models embed a basic understanding of track structure with statistical approaches of flow cytometry data sorted by cell cycle phase, and fluorescence intensity taking into account background levels. Following flow cytometry analysis, we were able to distinguish the kinetics of these phospho-proteins in relationship to the cell cycle and to each other in an individual cell. Results revealed a unique pattern of kinetics for high vs low LET radiation, with a failure to initiate full activation of the ATM pathway being evident following High LET exposure. In the process of these studies we have noted that different populations of cells making up normal human tissues can be sorted based on intrinsic qualities of the cells and differences in their radiation sensitivity have been noted. In addition, an increase in proliferation of a specific mammary cell population was observed with low doses of radiation.

Project D: DNA Damage in Cancer Initiation and Genomic Instability: Foci size and clustering including strings of foci along high-Z high-energy (HZE) tracks, were modeled for the first time and provide a useful analysis tool of NSRL experiments on DNA damage foci. These models have been extended to predict chromosomal aberration formation including the distribution of small rings normally below detection levels with fluorescence in-situ hybridization (FISH) (<5 Mbp), and to describe complex aberrations. Stochastic track structure models were combined with a human genome model that considers random walk polymer models of each chromosomes pair built from 2 kbp monomers and constrained to nuclear territories in interphase (Ponomarev et al., 2007, 2009).

Project E: Acute Radiation Risk Models: We extended the granulopoietic model for rodents for the prediction of solar particle effects in canines, non-human primates, and humans (Hu and Cucinotta, 2011). An important feature of this approach is that the dynamics of cell populations are described by non-linear differential equations. Validation of the model was achieved by comparison to comprehensive data sets for animals exposed to acute and chronic radiation and to the Chernobyl and other radiation accident victims.

Bibliography Type: Description: (Last Updated: 02/11/2021) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Ponomarev AL, Huff J, Cucinotta FA. "The analysis of the densely populated patterns of radiation-induced foci by a stochastic, Monte Carlo model of DNA double-strand breaks induction by heavy ions." International Journal of Radiation Biology. 2010 Jun;86(6):507-15. http://dx.doi.org/10.3109/09553001003717175 ; PubMed PMID: 20470200 , Jun-2010
Articles in Peer-reviewed Journals Chappell LJ, Whalen MK, Gurai S, Ponomarev A, Cucinotta FA, Pluth JM. "Analysis of flow cytometry DNA damage response protein activation kinetics after exposure to x rays and high-energy iron nuclei." Radiation Research 2010 Dec;174(6):691-702. Epub 2010 Sep 28. http://dx.doi.org/10.1667/RR2204.1 ; PubMed PMID: 21128792 , Dec-2010
Articles in Peer-reviewed Journals Cucinotta FA, Hu S, Schwadron NA, Kozarev K, Townsend LW, Kim MY. "Space radiation risk limits and Earth-Moon-Mars environmental models." Space Weather. 2010 Dec;8:S00E09. https://doi.org/10.1029/2010SW000572 , Dec-2010
Articles in Peer-reviewed Journals Hu S, Cucinotta FA. "Modelling the way Ku binds DNA." Radiation Protection Dosimetry. 2011 Feb;143(2-4):196-201. Epub 2010 Dec 31. http://dx.doi.org/10.1093/rpd/ncq519 ; PubMed PMID: 21196465 , Feb-2011
Articles in Peer-reviewed Journals Carra C, Cucinotta FA. "Binding selectivity of RecA to a single stranded DNA, a computational approach." Journal of Molecular Modeling. 2011 Jan;17(1):133-50. Epub 2010 Apr 13. PubMed PMID: 20386943 ; http://dx.doi.org/10.1007/s00894-010-0694-8 , Jan-2011
Articles in Peer-reviewed Journals Cucinotta FA, Plante I, Ponomarev AL, Kim MH. "Nuclear interactions in heavy ion transport and event-based risk models." Radiation Protection Dosimetry 2011 Feb;143(2-4):384-90. Review. Epub 2011 Jan 17. http://dx.doi.org/10.1093/rpd/ncq512 ; PubMed PMID: 21242169 , Feb-2011
Articles in Peer-reviewed Journals Kim MH, De Angelis G, Cucinotta FA. "Probabilistic assessment of radiation risk for astronauts in space missions." Acta Astronautica. 2011 Apr-May;68(7-8):747-59. http://dx.doi.org/10.1016/j.actaastro.2010.08.035 , Apr-2011
Articles in Peer-reviewed Journals Cucinotta FA, Chappell LJ. "Updates to astronaut radiation limits: radiation risks for never-smokers." Radiation Research. 2011 Jul;176(1):102-14. Epub 2011 May 16. PubMed PMID: 21574861 , Jul-2011
Articles in Peer-reviewed Journals Li Y, Cucinotta FA. "Modeling non-homologous end joining." Journal of Theoretical Biology. 2011 Aug 21;283(1):122-35. Epub 2011 May 24. http://dx.doi.org/10.1016/j.jtbi.2011.05.015 ; PubMed PMID: 21635903 , Aug-2011
Articles in Peer-reviewed Journals Hu S, Cucinotta FA. "Characterization of the radiation-damaged precursor cells in bone marrow based on modeling of the peripheral blood granulocytes response." Health Physics. 2011 Jul;101(1):67-78. http://dx.doi.org/10.1097/HP.0b013e31820dba65 ; PubMed PMID: 21617393 , Jul-2011
Articles in Peer-reviewed Journals Plante I, Ponomarev A, Cucinotta FA. "3D visualisation of the stochastic patterns of the radial dose in nano-volumes by a Monte Carlo simulation of HZE ion track structure." Radiation Protection Dosimetry. 2011 Feb;143(2-4):156-61. Epub 2011 Jan 2. http://dx.doi.org/10.1093/rpd/ncq526 ; PubMed PMID: 21199826 , Feb-2011
Articles in Peer-reviewed Journals Ponomarev A, Sundaresan A, Vazquez ME, Guida P, Kim A, Cucinotta FA. "A model of the effects of heavy ion irradiation on human tissue." Advances in Space Research 2011 Jan 4;47(1):37-48. http://dx.doi.org/10.1016/j.asr.2010.08.014 , Jan-2011
Articles in Peer-reviewed Journals Durante M, Cucinotta FA. "Physical basis of radiation protection in space travel." Reviews of Modern Physics. 2011 Oct-Dec;83(4):1245-81. http://dx.doi.org/10.1103/RevModPhys.83.1245 (Originally reported as "In press, as of August 2011.") , Oct-2011
Articles in Peer-reviewed Journals Kim MH, Qualls GD, Slaba TC, Cucinotta FA. "Comparison of organ dose and dose equivalent for human phantoms of CAM vs. MAX." Advances in Space Research. 2010 Apr 1;45(7):850-7. http://dx.doi.org/10.1016/j.asr.2009.09.027 , Apr-2010
Articles in Peer-reviewed Journals Cucinotta FA, Chappell LJ. "Non-targeted effects and the dose response for heavy ion tumor induction." Mutation Research. 2010 May 1;687(1-2):49-53. Epub 2010 Jan 18. http://dx.doi.org/10.1016/j.mrfmmm.2010.01.012 ; PubMed PMID: 20085778 , May-2010
Articles in Peer-reviewed Journals Hu S, Cucinotta FA. "A cell kinetic model of granulopoiesis under radiation exposure: extension from rodents to canines and humans." Radiation Protection Dosimetry. 2011 Feb;143(2-4):207-13. Epub 2010 Dec 31. http://dx.doi.org/10.1093/rpd/ncq520 ; PubMed PMID: 21196459 , Feb-2011
Articles in Peer-reviewed Journals Ponomarev AL, George K, Cucinotta FA. "Generalized time-dependent model of radiation-induced chromosomal aberrations in normal and repair-deficient human cells." Radiat Res. 2014 Mar;181(3):284-92. http://dx.doi.org/10.1667/RR13303.1 ; PubMed PMID: 24611656 , Mar-2014
Articles in Peer-reviewed Journals Li Y, Wang M, Carra C, Cucinotta FA. "Modularized Smad-regulated TGFß signaling pathway." Math Biosci. 2012 Dec;240(2):187-200. Epub 2012 Aug 6. http://dx.doi.org/10.1016/j.mbs.2012.07.005 ; PubMed PMID: 22892478 , Dec-2012
Articles in Peer-reviewed Journals Plante I, Cucinotta FA. "Model of the initiation of signal transduction by ligands in a cell culture: simulation of molecules near a plane membrane comprising receptors." Phys Rev E Stat Nonlin Soft Matter Phys. 2011 Nov;84(5 Pt 1):051920. PubMed PMID: 22181457 , Nov-2011
Articles in Peer-reviewed Journals Ray FA, Robinson E, McKenna M, Hada M, George K, Cucinotta F, Goodwin EH, Bedford JS, Bailey SM, Cornforth MN. "Directional genomic hybridization: inversions as a potential biodosimeter for retrospective radiation exposure." Radiat Environ Biophys. 2014 May;53(2):255-63. Epub 2014 Jan 30. http://dx.doi.org/10.1007/s00411-014-0513-1 ; PubMed PMID: 24477407 , May-2014
Articles in Peer-reviewed Journals Hu S, Cucinotta FA. "Epidermal homeostasis and radiation responses in a multiscale tissue modeling framework." Integr Biol (Camb). 2014 Jan;6(1):76-89. http://dx.doi.org/10.1039/c3ib40141c ; PubMed PMID: 24270511 , Jan-2014
Articles in Peer-reviewed Journals Smirnova OA, Hu S, Cucinotta FA. "Analysis of the lymphocytopoiesis dynamics in nonirradiated and irradiated humans: a modeling approach." Radiat Res. 2014 Mar;181(3):240-50. http://dx.doi.org/10.1667/RR13256.1 ; PubMed PMID: 24673256 , Mar-2014
Articles in Peer-reviewed Journals Hassler DM, Zeitlin C, Wimmer-Schweingruber RF, Ehresmann B, Rafkin S, Eigenbrode JL, Brinza DE, Weigle G, Böttcher S, Böhm E, Burmeister S, Guo J, Köhler J, Martin C, Reitz G, Cucinotta FA, Kim MH, Grinspoon D, Bullock MA, Posner A, Gómez-Elvira J, Vasavada A, Grotzinger JP; MSL Science Team. "Mars' surface radiation environment measured with the Mars Science Laboratory's Curiosity rover." Science. 2014 Jan 24;343(6169):1244797. http://dx.doi.org/10.1126/science.1244797 ; PubMed PMID: 24324275 , Jan-2014
Articles in Peer-reviewed Journals Posner A, Odstrcil D, MacNeice P, Rastaetter L, Zeitlin C, Heber B, Elliott H, Frahm RA, Hayes JJ, von Rosenvinge TT, Christian ER, Andrews JP, Beaujean R, Böttcher S, Brinza DE, Bullock MA, Burmeister S, Cucinotta FA, Ehresmann B, Epperly M, Grinspoon D, Guo J, Hassler DM, Kim M-H, Kohler J, Kortmann O, Martin Garcia C, Müller-Mellin R, Neal K, Rafkin SC, Reitz G, Seimetz L, Smith KD, Tyler Y, Weigle E, Wimmer-Schweingruber RF. "The Hohmann–Parker effect measured by the Mars Science Laboratory on the transfer from Earth to Mars: Consequences and opportunities." Planetary and Space Science. 2013 Dec;89(13):127-39. http://dx.doi.org/10.1016/j.pss.2013.09.013 , Dec-2013
Articles in Peer-reviewed Journals Cucinotta FA, Kim MH, Chappell LJ, Huff JL. "How safe is safe enough? Radiation risk for a human mission to Mars." PLoS One. 2013 Oct 16;8(10):e74988. eCollection 2013. http://dx.doi.org/10.1371/journal.pone.0074988 ; PubMed PMID: 24146746; PubMed Central PMCID: PMC3797711 , Oct-2013
Articles in Peer-reviewed Journals Yoshida K, Hada M, Eguchi-Kasai K, Teramura T, Cucinotta FA, Morita T. "Estimation of effects of space radiation using frozen mouse ES cells in ISS." J Radiat Res. 2014 Mar 1;55(Suppl 1):i12-i13. (Proceedings of Heavy Ion in Therapy and Space Radiation Symposium 2013, Chiba, Japan, May 15-18, 2013.) http://dx.doi.org/10.1093/jrr/rrt217 , Mar-2014
Articles in Peer-reviewed Journals Plante I, Ponomarev AL, Cucinotta FA. "Calculation of the energy deposition in nanovolumes by protons and HZE particles: geometric patterns of initial distributions of DNA repair foci." Phys Med Biol. 2013 Sep 21;58(18):6393-405. http://dx.doi.org/10.1088/0031-9155/58/18/6393 ; PubMed PMID: 23999659 , Sep-2013
Articles in Peer-reviewed Journals Plante I, Devryoe L, Cucinotta FA. "Calculations of distance distributions and probabilities of binding by ligands between parallel plane membranes comprising receptors." Computer Physics Communications. 2014 Mar;185(3):697-707. http://dx.doi.org/10.1016/j.cpc.2013.09.011 , Mar-2014
Articles in Peer-reviewed Journals Autsavapromporn N, Suzuki M, Funayama T, Usami N, Plante I, Yokota Y, Mutou Y, Ikeda H, Kobayashi K, Kobayashi Y, Uchihori Y, Hei TK, Azzam EI, Murakami T. "Gap junction communication and the propagation of bystander effects induced by microbeam irradiation in human fibroblast cultures: the impact of radiation quality." Radiat Res. 2013 Oct;180(4):367-75. Epub 2013 Aug 29. http://dx.doi.org/10.1667/RR3111.1 ; PubMed PMID: 23987132; PubMed Central PMCID: PMC4058832 , Oct-2013
Articles in Peer-reviewed Journals Sridharan DM, Roppel RD, Chan R, Wilson WC, Whalen MK, Chappell LJ, Pluth JM. "Small dose rate changes significantly affect the magnitude of cellular signaling in response to high LET exposure." J Radiat Res. 2014 Mar 1;55(Suppl 1):i75-i76. (Proceedings of Heavy Ion in Therapy and Space Radiation Symposium 2013, Chiba, Japan, May 15-18, 2013.) http://dx.doi.org/10.1093/jrr/rrt203 , Mar-2014
Articles in Peer-reviewed Journals Kim M-H, Cucinotta FA, Nounu HN, Zeitlin C, Hassler DM, Rafkin SC, Wimmer-Schweingruber RF, Ehresmann B, Brinza DE, Böttcher S, Bohm E, Burmeister S, Guo J, Kohler J, Martin C, Reitz G, Posner A, Gomez-Elvira J, Harri AM, MSL Science Team. "Comparison of Martian surface ionizing radiation measurements from MSL-RAD with Badhwar-O'Neill 2011/HZETRN model calculations." Journal of Geophysical Research Planets. 2014 Jun;119(6):1311-21. http://dx.doi.org/10.1002/2013JE004549 , Jun-2014
Articles in Peer-reviewed Journals Rafkin SC, Zeitlin C, Ehresmann B, Hassler DM, Guo J, Kohler J, Wimmer-Schweingruber RF, Gomez-Elvira J, Kahanpää H, Brinza DE, Weigle G, Böttcher S, Bohm E, Burmeister S, Martin C, Reitz G, Cucinotta FA, Kim M-H, Grinspoon D, Bullock MA, Posner A, MSL Science Team. "Diurnal variations of energetic particle radiation at the surface of Mars as observed by the Mars Science Laboratory Radiation Assessment Detector." Journal of Geophysical Research Planets. 2014 Jun;119(6):1345-58. http://dx.doi.org/10.1002/2013JE004525 , Jun-2014
Articles in Peer-reviewed Journals George KA, Hada M, Chappell L, Cucinotta FA. "Biological effectiveness of accelerated particles for the induction of chromosome damage: track structure effects." Radiat Res. 2013 Jul;180(1):25-33. http://dx.doi.org/10.1667/RR3291.1 ; 21. PubMed PMID: 23692480 , Jul-2013
Articles in Peer-reviewed Journals Hada M, Chappell LJ, Wang M, George KA, Cucinotta FA. "Induction of chromosomal aberrations at fluences of less than one HZE particle per cell nucleus." Radiat Res. 2014 Oct;182(4):368-79. http://dx.doi.org/10.1667/RR13721.1 ; PubMed PMID: 25229974 , Oct-2014
Articles in Peer-reviewed Journals Smirnova OA, Hu S, Cucinotta FA. "Dynamics of acutely irradiated skin epidermal epithelium in swine: modeling studies." Health Phys. 2014 Jul;107(1):47-59. PubMed PMID: 24849903 , Jul-2014
Articles in Peer-reviewed Journals George KA, Hada M, Cucinotta FA. "Biological effectiveness of accelerated protons for chromosome exchanges." Front Oncol. 2015 Oct 19;5:226. eCollection 2015. http://dx.doi.org/10.3389/fonc.2015.00226 ; PubMed PMID: 26539409; PubMed Central PMCID: PMC4610205 , Oct-2015
Articles in Peer-reviewed Journals Plante I, Cucinotta FA. "Simulation of the radiolysis of water using Green's functions of the diffusion equation." Radiat Prot Dosimetry. 2015 Sep;166(1-4):24-8. Epub 2015 Apr 20. http://dx.doi.org/10.1093/rpd/ncv179 ; PMID: 25897139 , Sep-2015
Articles in Peer-reviewed Journals Hada M, Saganti PB, Cucinotta FA. "Nitric oxide is involved in heavy ion-induced non-targeted effects in human fibroblasts." Int J Mol Sci. 2019 Sep 4;20(18):E4327. https://doi.org/10.3390/ijms20184327 ; PubMed PMID: 31487843 , Sep-2019
Articles in Peer-reviewed Journals Li Y, Reynolds P, O'Neill P, Cucinotta FA. "Modeling damage complexity-dependent non-homologous end-joining repair pathway." PLoS One. 2014 Feb 10;9(2):e85816. https://10.1371/journal.pone.0085816 ; PMID: 24520318; PMCID: PMC3919704 , Feb-2014
Significant Media Coverage NASA Tech Briefs. " 'Galactic Cosmic Ray Event-Based Risk Model (GERM) Code.' Article about work done by Francis A. Cucinotta of Johnson Space Center and Ianik Plante, Artem L. Ponomarev, and Myung- Hee Y. Kim of the Universities Space Research Association." NASA Tech Briefs, May 1, 2013. p. 27 (in print version). Item MSC-24760-1. http://www.techbriefs.com/component/content/article/ntb/tech-briefs/software/16350 , May-2013
Project Title:  Space Radiation Risk Assessment Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 06/01/2006  
End Date: 05/31/2011  
Task Last Updated: 12/30/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Cucinotta, Francis A Ph.D. / University of Nevada, Las Vegas 
Address:  Health Physics & Diagnostic Sciences / BHS-345 
4505 Maryland Parkway 
Las Vegas , NV 89154-3037 
Email: not available 
Phone: (702) 895-4320  
Congressional District:
Web:  
Organization Type: NASA CENTER 
Organization Name: University of Nevada, Las Vegas 
Joint Agency:  
Comments: Formerly at NASA Johnson Space Center, until summer 2013 (Ed., Oct 2013) 
Co-Investigator(s)
Affiliation: 
Pluth, Janice  LBNL 
Cornforth, Michael  U TX Medical Branch 
Ponomarev, Artem  USRA 
Kim, Myung-Hee  USRA 
Qualles, Garry  NASA Langley 
Carra, Claudio  USRA Division of Life Sciences 
Key Personnel Changes / Previous PI: Dr. Deepa Sridharan joined the project as a Post-doc at LBNL. Dr Zarana Patel left the project from USRA in Houston
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) ARS:Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs)
(2) Cancer:Risk of Radiation Carcinogenesis
(3) CNS:Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure (IRP Rev G)
(4) Degen:Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure (IRP Rev F)
Human Research Program Gaps: (1) Acute02:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict acute radiation risks in astronauts? How can human epidemiology data best support these procedures or models?
(2) Acute06:What are the most effective shielding approaches to mitigate acute radiation risks, how do we know, and implement?
(3) Acute08:How can Probabilistic risk assessment be applied to SPE risk evaluations for EVA, and combined EVA+IVA exposures?
(4) Cancer03:How can experimental models of carcinogenesis be applied to reduce the uncertainties in radiation quality effects from SPEs and GCR, including effects on tumor spectrum, burden, latency and progression (e.g., tumor aggression and metastatic potential)? (IRP Rev F)
(5) Cancer04:How can models of cancer risk be applied to reduce the uncertainties in dose-rate dependence of risks from SPEs and GCR?
(6) Cancer05:How can models of cancer risk be applied to reduce the uncertainties in individual radiation sensitivity including genetic and epigenetic factors from SPE and GCR?
(7) Cancer06:How can models of cancer risk be applied to reduce the uncertainties in the age and gender dependence of cancer risks from SPEs and GCR?
(8) Cancer07:How can systems biology approaches be used to integrate research on the molecular, cellular, and tissue mechanisms of radiation damage to improve the prediction of the risk of cancer and to evaluate the effectiveness of CMs? How can epidemiology data and scaling factors support this approach?
(9) Cancer11:What are the most effective shielding approaches to mitigate cancer risks?
(10) Cancer12:What quantitative models, numerical methods, and experimental data are needed to accurately describe the primary space radiation environment and transport through spacecraft materials and tissue to evaluate dose composition in critical organs for mission relevant radiation environments (ISS, Free-space, Lunar, or Mars)? (IRP Rev F)
(11) CBS-CNS-5:How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE? (IRP Rev F)
(12) CNS06:How can new knowledge and data from molecular, cellular, tissue and animal models of late CNS risks or clinical human data be used to estimate late CNS risks to astronauts from GCR and SPE?
(13) Degen05:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict degenerative tissue risks in astronauts? How can human epidemiology data best support these procedures or models?
Task Description: The Risk Assessment Project at Johnson Space Center is responsible for the integration of results from NASA space radiobiology research into computational models used for astronaut radiation risk assessments. The purpose of the Project is fourfold: (1) evaluate the extent to which ongoing research leads to reduction in the uncertainty of risk assessments and provide, as a metric of program progress, the number of days in space during which the radiation exposure of astronauts remains below NASA limits within a 95% confidence interval (“safe days in space”); (2) perform mission planning studies to predict the number of safe days for any mission; (3) assess the radiation risk to astronauts for ongoing missions in real time; and, (4) provide recommendations for research directions most likely to reduce risk or improve the accuracy of risk predictions.

The four categories of risks from radiation in space are defined by the NASA Bioastronautics Roadmap (BR). They are: 1) Carcinogenesis, 2) Acute and late effects to the Central Nervous System (CNS), 3) Degenerative Tissue Effects such as heart disease and cataracts, and 4) Acute Radiation risks. The number of safe days currently predicted for an astronaut’s career is less than required by mission planning, due to the large uncertainties in risk prediction. In particular, a projection uncertainty below + or - 50% is the goal for the 1000-day Mars mission because the high level of risk will require high precision risk evaluations. The current approach used to project risk is based on epidemiology data and on phenomenological models used to derive risk prediction from them. This approach cannot lead to improvements in the accuracy of risk prediction beyond a factor of approximately 2. New approaches using molecular biology and genetics are the only viable ones for achieving the level of accuracy required by space exploration and a robust program to obtain the required data is supported by the Space Radiation Program. However, how to incorporate these data into risk prediction and assessment models is not well understood. This Project Plan describes the approaches that will be used to develop models of risk assessment based on mechanistic space radiobiology research funded by the Space Radiation Program, leading to incremental uncertainty reduction based on new experimental data, and to the development of application software to be used in the NASA operational radiation protection program. To accomplish these goals, we will establish new molecular based models of risk. The molecular pathways that are the hallmarks of genomic instability and cancer, and the perturbation of these pathways by radiation will be described using systems biology approaches and Monte-Carlo simulation. We will develop descriptive models of such pathways utilizing track structure models of biomolecular damage, and deterministic and stochastic kinetic models of dominant molecular pathways causative of BR radiation risks. These simulations will make maximum use of results from mechanistic space radiobiology, and will replace traditional hazard functions and their inherent uncertainties due to reliance on epidemiological or phenomenological approaches.

Research Impact/Earth Benefits: Radiobiology research provides many important qualitative descriptions of biological effects of radiation on biomolecules, cells, and tissues. The Space Radiation Risk Assessment Project provides an important link that integrates qualitative experimental observations into detailed quantitative biophysical models of radiations risks. This research benefits all humans that will be exposed to ionizing radiation and supports the development of disease models in general.

Models of cancer, CNS, heart disease, acute and other risks developed by the Space Radiation Risk Assessment Project provide NASA with the ability to project risks and develop cost-effective mitigation approaches for future exploration missions.

Task Progress & Bibliography Information FY2009 
Task Progress: The translation of research findings into models of risks and their application to the discovery of new biological knowledge, space mission risk estimates, and exploration mission planning was achieved in several areas. In the period of performance a Graphical User Interface (GUI) for the Acute Radiation Risk Body Organ Dose (ARRBOD) model was developed and released as a Beta version. ARRBOD uses the BRYNTRN code to calculate organ doses from solar particle events (SPE) and to evaluate risk of prodromal effects. Efforts to integrate physics and biophysics models of space radiation into a collaborative modeling framework made great progress in the 3rd Year of performance. A stochastic physics model was developed to characterize particle beams and secondaries for experiments at the NASA Space Radiation Laboratory (NSRL). The resulting model called the GCR Event-Based Risk Model (GERMcode) is based on Monte-Carlo algorithms for forward-backward ion transport. This will allow for ray tracing techniques such as the ProE FISHBOWL tool to be seamlessly integrated into a future space version of the GERMcode. Excellent agreement between the GERMcode and NSRL data was found. A beta-version of the GERMcode GUI was released.

Cancer risk model updates were completed including: comparison of the BEIR VII, UNSCEAR and NCRP models, development of new tissue weighting factors appropriate for astronauts, preliminary recommendations of new solid cancer and leukemia specific quality factors, and new developments of dose response models for non-targeted effects for heavy ion carcinogenesis. The non-targeted effects model suggest much higher cancer risks at low doses of heavy ions than the conventional model recommended by the NCRP. New probability distribution functions (PDF) to represent the uncertainties in new and existing data sets and knowledge of radiation quality effects, dose-rate modifiers, and the dependecies of risk on age at exposure are being considered from these analyses. Heart disease risk estimates were developed using a triple detriment approach based on US population data for coronary heart disease and stroke and recent meta-analysis of excess relative risks in exposed cohorts. Values of RBEs and dose-rate modifiers for heart disease are being investigated, and suggest a wide range of possibilities for the mortality risks from heart disease with results ranging from negligible to radiation cancer risks to approaching ½ of the cancer risk of males of above age 45 y at the time of exposure. A mathematical representation of the two-hit model of Alzheimer’s disease was developed. The model can be used to estimate a shift in the age of appearance of Alzheimer’s disease based on the number of neuronal cells with radiation induced hits.

Systems biology model developments included new molecular dynamic calculations of the Ku70/80 protein, RecA, and preliminary results for the RPA and Smad protein interactions with DNA. Computational tools to assess DNA repair foci and flow cytometry data for signal transduction phospho-proteins were developed. New flow based assays for dually staining proteins, cell population kinetics and telomere shortening were considered. A stochastic model of ligand-receptor binding to model TGFbeta activation was developed using a Green’s function approach.

A non-linear model of granulocytopoiesis following acute or chronic irradiation was compared to experimental data for several mammalian species and extended to human exposures including blood level kinetics following exposures to solar particle events. A probabilistic approach to solar particle event organ dose evaluation and shielding design was developed. These models will form the basis for ARRBOD V2.0

Bibliography Type: Description: (Last Updated: 02/11/2021) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Cucinotta FA, Kim MH, Willingham V, George KA. "Physical and biological organ dosimetry analysis for International Space Station Astronauts." Radiation Research 2008 Jul;170(1):127-38. http://dx.doi.org/10.1667/RR1330.1 ; PMID: 18582161 , Jul-2008
Articles in Peer-reviewed Journals Ponomarev AL, Costes SV, Cucinotta FA. "Stochastic properties of radiation induced DSB: DSB distributions in large scale chromatin loops, the HPRT gene and within the visible volumes of DNA repair foci." International Journal of Radiation Biology 2008 Nov;84(11):916-29. http://dx.doi.org/10.1080/09553000802499212 ; PMID: 19016140 , Nov-2008
Articles in Peer-reviewed Journals Plante I, Cucinotta FA. "Ionization and excitation cross sections for the interaction of HZE particles in liquid water and application to Monte-Carlo simulation of radiation tracks." New Journal of Physics 2008 Dec;10:125020 , 1367-74. https://inis.iaea.org/search/search.aspx?orig_q=RN:41004107 ; http://dx.doi.org/10.1088/1367-2630/10/12/125020 , Dec-2008
Articles in Peer-reviewed Journals Reitz G, Berger T, Bilski P, Facius R, Hajek M, Petrov V, Puchalska M, Zhou D, Bossler J, Akatov Y, Shurshakov V, Olko P, Ptaszkiewicz M, Bergmann R, Fugger M, Vana N, Beaujean R, Burmeister S, Bartlett D, Hager L, Pálfalvi J, Szabó J, O'Sullivan D, Kitamura H, Uchihori Y, Yasuda N, Nagamatsu A, Tawara H, Benton E, Gaza R, McKeever S, Sawakuchi G, Yukihara E, Cucinotta F, Semones E, Zapp N, Miller J, Dettmann J. "Astronaut’s organ doses inferred from measurements in a human phantom outside the International Space Station." Radiation Research 2009 Feb;171(2):225-35. http://dx.doi.org/10.1667/RR1559.1 ; PubMed PMID: 19267549 , Feb-2009
Articles in Peer-reviewed Journals Valtonen V, Nurmi P, Zheng JQ, Cucinotta FA, Wilson JW, Horneck G, Lindegren L, Melosh J, Rickman H, Mileikowsky C. "Natural transfer of viable microbes in space from planets in extra-solar systems to a planet in our solar system and vice versa." Astrophysical Journal. 2009 Jan 1;690(1):210-5. https://arxiv.org/abs/0809.0378 , Jan-2009
Articles in Peer-reviewed Journals Kim MH, Hayat MJ, Feiveson AH, Cucinotta FA. "Prediction of frequency and exposure level of solar particle events." Health Physics 2009 Jul;97(1):68-81. http://dx.doi.org/10.1097/01.HP.0000346799.65001.9c ; PubMed PMID: 19509510 , Jul-2009
Articles in Peer-reviewed Journals Hu S, Kim MH, McClellan GE, Cucinotta FA. "Modeling the acute health effects of astronauts from exposure to large solar particle events" Health Physics 2009 Apr;96(4):465-76. http://dx.doi.org/10.1097/01.HP.0000339020.92837.61 ; PubMed PMID: 19276707 , Apr-2009
Articles in Peer-reviewed Journals Kim MY, Hayat ML, Feiveson AH, Cucinotta FA. "Using high-energy proton fluence to improve risk prediction for consequences of solar particle events." Advances in Space Research 2009 Dec 15;44(12):1428-32. http://dx.doi.org/10.1016/j.asr.2009.07.028 , Dec-2009
Articles in Peer-reviewed Journals Carra C, Cucinotta FA. "Binding sites of the E. Coli DNA recombinase protein to the ssDNA: a computational study." J Biomol Struct Dyn. 2010 Feb;27(4):407-28. PubMed PMID: 19916564 , Feb-2010
Articles in Peer-reviewed Journals Plante I, Cucinotta FA. "Cross sections for the interactions of 1 eV–100 MeV electrons in liquid water and application to Monte-Carlo simulation of HZE radiation tracks." New Journal of Physics 2009 Jun;11(6):063047 , p. 1-24. https://inis.iaea.org/search/search.aspx?orig_q=RN:41041472 ; http://dx.doi.org/10.1088/1367-2630/11/6/063047 , Jun-2009
Articles in Peer-reviewed Journals Chappell LJ, Whalen MK, Gurai S, Ponomarev A, Cucinotta FA, Pluth JM. "Analysis of flow cytometry DNA damage response protein activation kinetics after exposure to X rays and high-energy iron nuclei." Radiation Research. Submitted January 2010. , Jan-2010
Articles in Peer-reviewed Journals Plante I, Cucinotta FA. "Energy deposition and relative frequency of hits of cylindrical nanovolume in medium irradiated by ions: Monte Carlo simulation of tracks structure." Radiat Environ Biophys. 2010 Mar;49(1):5-13. http://dx.doi.org/10.1007/s00411-009-0255-7 ; PMID: 19916014 (originally reported as 2009 Nov 15. [Epub ahead of print] in December 2009) , Mar-2010
Articles in Peer-reviewed Journals Cucinotta FA, Chappell LJ. "Non-targeted effects and the dose response for heavy ion tumor induction." Mutation Research. In press, January 2010. , Jan-2010
Articles in Peer-reviewed Journals Kim MH, Qualls GD, Slaba TC, Cucinotta FA. "Comparison of organ dose and dose equivalent for human phantoms of CAM vs. MAX." Advances in Space Research. In press, January 2010. , Jan-2010
Articles in Peer-reviewed Journals Ponomarev AL, Huff J, Cucinotta FA. "The analysis of the densely populated patterns of radiation-induced foci by a stochastic, Monte Carlo model of DNA double-strand breaks induction by heavy ions." Int J Radiat Biol. Submitted, December 2009. , Dec-2009
Articles in Peer-reviewed Journals Hu S, Cucinotta FA. "A cell kinetic model of granulopoiesis under radiation exposure: Extension from rodents to canines and humans." Radiation Protection Dosimetry. Submitted January 2010. , Jan-2010
NASA Technical Documents Nounu HN, Kim MY, Ponomarev AL, Cucinotta FA. "The Use of Pro/ENGINEER CAD Software and Fishbowl Toolkit in Ray-tracing Analysis." Washington, DC : NASA, 2009. NASA technical paper ; 2009-214788. NASA TP-2009-214788 , Jun-2009
Project Title:  Space Radiation Risk Assessment Reduce
Fiscal Year: FY 2008 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 06/01/2006  
End Date: 05/31/2011  
Task Last Updated: 01/18/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Cucinotta, Francis A Ph.D. / University of Nevada, Las Vegas 
Address:  Health Physics & Diagnostic Sciences / BHS-345 
4505 Maryland Parkway 
Las Vegas , NV 89154-3037 
Email: not available 
Phone: (702) 895-4320  
Congressional District:
Web:  
Organization Type: NASA CENTER 
Organization Name: University of Nevada, Las Vegas 
Joint Agency:  
Comments: Formerly at NASA Johnson Space Center, until summer 2013 (Ed., Oct 2013) 
Co-Investigator(s)
Affiliation: 
Pluth, Janice M LBNL 
Cornforth, Michael  U TX Medical Branch 
George, Kerry  Wylie Labs 
Ponomarev, Artem  USRA 
Huff, Janice  USRA 
Kim, Myung-Hee  USRA 
Qualles, Garry  NASA Langley 
Clowdsley, Martha  NASA Langley 
Key Personnel Changes / Previous PI: Dr. Nikjoo has left the Project
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) ARS:Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs)
(2) Cancer:Risk of Radiation Carcinogenesis
(3) CNS:Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure (IRP Rev G)
(4) Degen:Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure (IRP Rev F)
Human Research Program Gaps: (1) Acute02:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict acute radiation risks in astronauts? How can human epidemiology data best support these procedures or models?
(2) Acute06:What are the most effective shielding approaches to mitigate acute radiation risks, how do we know, and implement?
(3) Acute08:How can Probabilistic risk assessment be applied to SPE risk evaluations for EVA, and combined EVA+IVA exposures?
(4) Cancer03:How can experimental models of carcinogenesis be applied to reduce the uncertainties in radiation quality effects from SPEs and GCR, including effects on tumor spectrum, burden, latency and progression (e.g., tumor aggression and metastatic potential)? (IRP Rev F)
(5) Cancer04:How can models of cancer risk be applied to reduce the uncertainties in dose-rate dependence of risks from SPEs and GCR?
(6) Cancer05:How can models of cancer risk be applied to reduce the uncertainties in individual radiation sensitivity including genetic and epigenetic factors from SPE and GCR?
(7) Cancer06:How can models of cancer risk be applied to reduce the uncertainties in the age and gender dependence of cancer risks from SPEs and GCR?
(8) Cancer07:How can systems biology approaches be used to integrate research on the molecular, cellular, and tissue mechanisms of radiation damage to improve the prediction of the risk of cancer and to evaluate the effectiveness of CMs? How can epidemiology data and scaling factors support this approach?
(9) Cancer11:What are the most effective shielding approaches to mitigate cancer risks?
(10) Cancer12:What quantitative models, numerical methods, and experimental data are needed to accurately describe the primary space radiation environment and transport through spacecraft materials and tissue to evaluate dose composition in critical organs for mission relevant radiation environments (ISS, Free-space, Lunar, or Mars)? (IRP Rev F)
(11) CBS-CNS-5:How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE? (IRP Rev F)
(12) CNS06:How can new knowledge and data from molecular, cellular, tissue and animal models of late CNS risks or clinical human data be used to estimate late CNS risks to astronauts from GCR and SPE?
(13) Degen05:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict degenerative tissue risks in astronauts? How can human epidemiology data best support these procedures or models?
Task Description: The Risk Assessment Project at Johnson Space Center is responsible for the integration of results from NASA space radiobiology research into computational models used for astronaut radiation risk assessments. The purpose of the Project is fourfold: (1) evaluate the extent to which ongoing research leads to reduction in the uncertainty of risk assessments and provide, as a metric of program progress, the number of days in space during which the radiation exposure of astronauts remains below NASA limits within a 95% confidence interval (“safe days in space”); (2) perform mission planning studies to predict the number of safe days for any mission; (3) assess the radiation risk to astronauts for ongoing missions in real time; and, (4) provide recommendations for research directions most likely to reduce risk or improve the accuracy of risk predictions. The four categories of risks from radiation in space are defined by the NASA Bioastronautics Roadmap (BR). They are: 1) Carcinogenesis, 2) Acute and late effects to the Central Nervous System (CNS), 3) Degenerative Tissue Effects such as heart disease and cataracts, and 4) Acute Radiation risks. The number of safe days currently predicted for an astronaut’s career is less than required by mission planning, due to the large uncertainties in risk prediction. In particular, a projection uncertainty below + or - 50% is the goal for the 1000-day Mars mission because the high level of risk will require high precision risk evaluations. The current approach used to project risk is based on epidemiology data and on phenomenological models used to derive risk prediction from them. This approach cannot lead to improvements in the accuracy of risk prediction beyond a factor of approximately 2. New approaches using molecular biology and genetics are the only viable ones for achieving the level of accuracy required by space exploration and a robust program to obtain the required data is supported by the Space Radiation Program. However, how to incorporate these data into risk prediction and assessment models is not well understood. This Project Plan describes the approaches that will be used to develop models of risk assessment based on mechanistic space radiobiology research funded by the Space Radiation Program, leading to incremental uncertainty reduction based on new experimental data, and to the development of application software to be used in the NASA operational radiation protection program. To accomplish these goals, we will establish new molecular based models of risk. The molecular pathways that are the hallmarks of genomic instability and cancer, and the perturbation of these pathways by radiation will be described using systems biology approaches and Monte-Carlo simulation. We will develop descriptive models of such pathways utilizing track structure models of biomolecular damage, and deterministic and stochastic kinetic models of dominant molecular pathways causative of BR radiation risks. These simulations will make maximum use of results from mechanistic space radiobiology, and will replace traditional hazard functions and their inherent uncertainties due to reliance on epidemiological or phenomenological approaches.

Research Impact/Earth Benefits: Radiobiology research provides many important qualitative descriptions of biological effects of radiation on biomolecules, cells, and tissues. The Space Radiation Risk Assessment Project provides an important link that integrates qualitative experimental observations into detailed quantitative biophysical models of radiations risks. This research benefits all humans that will be exposed to ionizing radiation.

Models of cancer, acute and other risks developed by the Space Radiation Risk Assessment Project provide NASA with the ability to project risks and develop cost-effective mitigation approaches for future exploration missions.

Task Progress & Bibliography Information FY2008 
Task Progress: Extensive reviews of the field were made leading to the publication of Evidence Based Chapters for Cancer, CNS, Degenerative, and Acute risks to be included in the Human Research Program's Evidence Book. Also, a review of heavy ion carcinogenesis research was published in the journal, Nature Reviews Cancer.

The NASA Cancer risk projection model was further developed to estimate organ specific cancer risks. A review of NASA Space Radiation sponsored publications, or other data on RBE's for solid cancer and leukemia including surrogate markers is underway to formulate organ specific quality factors. The anatomical human geometry model, CAMERA was compared to spaceflight agreement with overall consistency of <15% found for Space Shuttle and ISS results. A new CT-based VOXEL model was compared to the CAMERA model and agreed very well (<5% difference) for GCR and hard SPE spectra. The effects of background cancer rates and survival curves were estimated through comparison of space radiation cancer risks for each of the 50 states using multiplicative and weighted multiplicative and additive risk transfer models. System biology models were developed for the ATM and TGF-beta pathways. Mechanisms that could lead to differences between signaling between low and high dose or LET were identified and will be further investigated. Of interest are the biochemical description of non-targeted effects through inter-cellular signaling. Also new computational tools to understand DNA damage repair foci and flow cytometry results with heavy ion beams were developed. Work on molecular dynamics simulations of the Ku and Rad51 proteins interacting with DNA were completed and identified likely binding regions on these proteins, and predictions of binding energies were made. ITC and FRET methods are being considered to verify computational predictions.

A Monte-Carlo track structure code, RITRACK was developed for relativistic heavy ion descriptions. The code includes the production and energy deposition of secondary electrons (delta-rays) with energies up to 10 MeV, and ions with energies from 0.1 MeV/u to 50 GeV/u. Track structure models of chromosomal aberrations using the random walk polymer models of the entire human genome were formulated and show good agreement with experiments.

Probabilistic risk assessment (PRA) tools were developed for SPE risks including the Acute radiation syndromes. A data base for energy spectra of all SPE's in the space era was developed and Hazard functions and sampling schemes formulated to consider shielding designs under PRA. This is the first PRA tool developed that considers SPE frequency of occurence, event size, and event spectral characteristics. The results will be very informative to the NASA Constellation program and the assessment of shielding approaches and mission architectures.

Bibliography Type: Description: (Last Updated: 02/11/2021) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Cucinotta FA. "The NASA Space Radiation Risk Assessment Project. " Presented at COSPAR Meeting, Montreal, Canada, July 2008.

COSPAR Meeting, Montreal, Canada, July 2008. , Jul-2008

Abstracts for Journals and Proceedings Cucinotta FA, Plante I, Whalen M, Pluth JM. "Computational Methods of HZE Nuclei Induced Signal Transduction." 19th Annual NASA Space Radiation Investigators’ Workshop, Philadelphia, PA, June 30-July 2, 2008.

19th Annual NASA Space Radiation Investigators’ Workshop, Philadelphia, PA, June 30-July 2, 2008. , Jul-2008

Abstracts for Journals and Proceedings Anderson JA, Harper JV, Cucinotta FA, O’Neill P. "The repairability of DNA damage: dependence on ionization density and cell cycle." 19th Annual NASA Space Radiation Investigators’ Workshop, Philadelphia, PA, June 30-July 2, 2008.

19th Annual NASA Space Radiation Investigators’ Workshop, Philadelphia, PA, June 30-July 2, 2008. , Jul-2007

Abstracts for Journals and Proceedings Ponomarev AL, Costes SV, Huff J, Patel Z, Cucinotta FA. "A Monte Carlo Model of Heavy Ion Irradiation of Chromosomes and an Image Segmentation Algorithm in the Analysis of DNA Damage Focus Statistics." 19th Annual NASA Space Radiation Investigators’ Workshop, Philadelphia, PA, June 30-July 2, 2008.

19th Annual NASA Space Radiation Investigators’ Workshop, Philadelphia, PA, June 30-July 2, 2008. , Jul-2008

Abstracts for Journals and Proceedings Kim MY, Cucinotta FA, Qualls GD, Slaba TC. "Comparison of Organ Dose and Dose Equivalent Using Ray Tracing of Phantoms to Space Flight Phantom Torso Data." COSPAR Meeting, Montreal, Canada, July 2008.

COSPAR Meeting, Montreal, Canada, July 2008. , Jul-2008

Articles in Peer-reviewed Journals Cucinotta FA, Pluth JM, Anderson JA, Harper JV, O'Neill P. "Biochemical kinetics model of DSB repair and induction of gamma-H2AX foci by non-homologous end joining." Radiat Res. 2008 Feb;169(2):214-22. http://dx.doi.org/10.1667/RR1035.1 ; PMID: 18220463 , Feb-2008
Articles in Peer-reviewed Journals Cucinotta FA, Kim MH, Willingham V, George KA. "Physical and biological organ dosimetry analysis for International Space Station astronauts." Radiat Res. 2008 Jul;170(1):127-38. http://dx.doi.org/10.1667/RR1330.1 ; PMID: 18582161 , Jul-2008
Articles in Peer-reviewed Journals Durante M, Cucinotta FA. "Heavy ion carcinogenesis and human space exploration." Nature Reviews Cancer. 2008 Jun;8(6):465-72. http://dx.doi.org/10.1038/nrc2391 ; PMID: 18451812 , Jun-2008
Articles in Peer-reviewed Journals Ponomarev AL, Costes SV, Cucinotta FA. "Stochastic properties of radiation-induced DSB: DSB distributions in large scale chromatin loops, the HPRT gene and within the visible volumes of DNA repair foci." Int J Radiat Biol. 2008 Nov;84(11):916-29. http://dx.doi.org/10.1080/09553000802499212 ; PMID: 19016140 , Nov-2008
Project Title:  Space Radiation Risk Assessment Reduce
Fiscal Year: FY 2007 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 06/01/2006  
End Date: 05/31/2011  
Task Last Updated: 01/04/2008 
Download report in PDF pdf
Principal Investigator/Affiliation:   Cucinotta, Francis A Ph.D. / University of Nevada, Las Vegas 
Address:  Health Physics & Diagnostic Sciences / BHS-345 
4505 Maryland Parkway 
Las Vegas , NV 89154-3037 
Email: not available 
Phone: (702) 895-4320  
Congressional District:
Web:  
Organization Type: NASA CENTER 
Organization Name: University of Nevada, Las Vegas 
Joint Agency:  
Comments: Formerly at NASA Johnson Space Center, until summer 2013 (Ed., Oct 2013) 
Co-Investigator(s)
Affiliation: 
Pluth, Janice  LBNL 
Cornforth, Michael  U TX Medical Branch 
George, Kerry  Wyle Labs 
Ponomarev, Artem  USRA 
Nikjoo, Hooshang   USRA 
Huff, Janice  USRA 
Kim, Myung-Hee  USRA 
Qualles, Garry  NASA Langley 
Clowdsley, Martha  NASA Langley 
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) ARS:Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs)
(2) Cancer:Risk of Radiation Carcinogenesis
(3) CNS:Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure (IRP Rev G)
(4) Degen:Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure (IRP Rev F)
Human Research Program Gaps: (1) Acute02:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict acute radiation risks in astronauts? How can human epidemiology data best support these procedures or models?
(2) Acute06:What are the most effective shielding approaches to mitigate acute radiation risks, how do we know, and implement?
(3) Acute08:How can Probabilistic risk assessment be applied to SPE risk evaluations for EVA, and combined EVA+IVA exposures?
(4) Cancer03:How can experimental models of carcinogenesis be applied to reduce the uncertainties in radiation quality effects from SPEs and GCR, including effects on tumor spectrum, burden, latency and progression (e.g., tumor aggression and metastatic potential)? (IRP Rev F)
(5) Cancer04:How can models of cancer risk be applied to reduce the uncertainties in dose-rate dependence of risks from SPEs and GCR?
(6) Cancer05:How can models of cancer risk be applied to reduce the uncertainties in individual radiation sensitivity including genetic and epigenetic factors from SPE and GCR?
(7) Cancer06:How can models of cancer risk be applied to reduce the uncertainties in the age and gender dependence of cancer risks from SPEs and GCR?
(8) Cancer07:How can systems biology approaches be used to integrate research on the molecular, cellular, and tissue mechanisms of radiation damage to improve the prediction of the risk of cancer and to evaluate the effectiveness of CMs? How can epidemiology data and scaling factors support this approach?
(9) Cancer11:What are the most effective shielding approaches to mitigate cancer risks?
(10) Cancer12:What quantitative models, numerical methods, and experimental data are needed to accurately describe the primary space radiation environment and transport through spacecraft materials and tissue to evaluate dose composition in critical organs for mission relevant radiation environments (ISS, Free-space, Lunar, or Mars)? (IRP Rev F)
(11) CBS-CNS-5:How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE? (IRP Rev F)
(12) CNS06:How can new knowledge and data from molecular, cellular, tissue and animal models of late CNS risks or clinical human data be used to estimate late CNS risks to astronauts from GCR and SPE?
(13) Degen05:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict degenerative tissue risks in astronauts? How can human epidemiology data best support these procedures or models?
Task Description: The Risk Assessment Project at Johnson Space Center is responsible for the integration of results from NASA space radiobiology research into computational models used for astronaut radiation risk assessments. The purpose of the Project is fourfold: (1) evaluate the extent to which ongoing research leads to reduction in the uncertainty of risk assessments and provide, as a metric of program progress, the number of days in space during which the radiation exposure of astronauts remains below NASA limits within a 95% confidence interval (“safe days in space”); (2) perform mission planning studies to predict the number of safe days for any mission; (3) assess the radiation risk to astronauts for ongoing missions in real time; and, (4) provide recommendations for research directions most likely to reduce risk or improve the accuracy of risk predictions. The four categories of risks from radiation in space are defined by the NASA Bioastronautics Roadmap (BR). They are: 1) Carcinogenesis, 2) Acute and late effects to the Central Nervous System (CNS), 3) Degenerative Tissue Effects such as heart disease and cataracts, and 4) Acute Radiation risks. The number of safe days currently predicted for an astronaut’s career is less than required by mission planning, due to the large uncertainties in risk prediction. In particular, a projection uncertainty below + or - 50% is the goal for the 1000-day Mars mission because the high level of risk will require high precision risk evaluations. The current approach used to project risk is based on epidemiology data and on phenomenological models used to derive risk prediction from them. This approach cannot lead to improvements in the accuracy of risk prediction beyond a factor of approximately 2. New approaches using molecular biology and genetics are the only viable ones for achieving the level of accuracy required by space exploration and a robust program to obtain the required data is supported by the Space Radiation Program. However, how to incorporate these data into risk prediction and assessment models is not well understood. This Project Plan describes the approaches that will be used to develop models of risk assessment based on mechanistic space radiobiology research funded by the Space Radiation Program, leading to incremental uncertainty reduction based on new experimental data, and to the development of application software to be used in the NASA operational radiation protection program. To accomplish these goals, we will establish new molecular based models of risk. The molecular pathways that are the hallmarks of genomic instability and cancer, and the perturbation of these pathways by radiation will be described using systems biology approaches and Monte-Carlo simulation. We will develop descriptive models of such pathways utilizing track structure models of biomolecular damage, and deterministic and stochastic kinetic models of dominant molecular pathways causative of BR radiation risks. These simulations will make maximum use of results from mechanistic space radiobiology, and will replace traditional hazard functions and their inherent uncertainties due to reliance on epidemiological or phenomenological approaches.

Research Impact/Earth Benefits: Radiobiology research provides many important qualitative descriptions of biological effects of radiation on biomolecules, cells, and tissues. The Space Radiation Risk Assessment Project provides an important link that integrates qualitative experimental observations into detailed quantitative biophysical models of radiations risks. This research benefits all humans that will be exposed to ionizing radiation.

Models of cancer, acute and other risks developed by the Space Radiation Risk Assessment Project provide NASA with the ability to project risks and develop cost-effective mitigation approaches for future exploration missions.

Task Progress & Bibliography Information FY2007 
Task Progress: The NASA cancer risk projection model was updated with new excess relative risks and excess additive risk coefficients recommended by the BEIR VII report and in recent publications from the RERF in Hiroshima. The age at exposure dependence of cancer risks is a critical factor in these newer models, and displays a much slower change with age than the models described in NCRP Report No. 132. A cancer incidence data base was developed and a publication is in preparation. Uncertainty analysis for the new Dose and dose-rate reduction effectiveness factors (DDREF) and age dependence of cancer risks are being updated for the NASA model.

Progress was made in developing systems biology models of the double strand break repair (DSB). In mammalian cells there are two mechanisms of DNA double strand break repair: Non-homologous end-joining (NHEJ) and homologous recombination (HR). The error-prone NHEJ is the main mechanism in resting cells and the G1 phase of the cell cycle. A systems biology model (Cucinotta et al., in press) of the NHEJ pathway was developed and used to make quantitative descriptions of the gamma-H2AX foci and DSB rejoining experiments. The model includes a kinetics description of several DNA repair proteins including the Ku70/80 hetero-dimer, the catalytic sub-unit of the DNA-PK repair complex denoted DNA-PKcs, and the Ligase-IV/XRCC4 complex. The regulation of DNA-PKcs by autophosphorylation for simple and complex DSB was described. The model is being extended to consider the radiation quality dependence of the relative fraction of simple and complex DSB, rejoining and associated repair defects, and the kinetics of various radiation induced foci (RIF). In further work, the addition of ATM and the MRN complex to the model was achieved and the role of processing of damaged ends by the Artemis and WRN proteins are being modeled

For biophysical understanding of sub-tissue structures a description of cell size and shape, and geometry of multiple cell lineages is needed. A “tissue box” model (Ponomarev and Cucinotta, 2006) was developed to represent heterogeneous tissue architecture and to score HZE tracks and nuclear reactions in 2D and 3D tissues. Accurate segmentation of imaging data from 2D or 3D from a variety of imaging methodologies is possible. The tissue box model will be applied to represent experimental models used by SRP funded investigators. Nuclear reactions were shown to be rare in a small tissue sample (<100 cubic-micron), however the possibility of a large imparted dose at such sites is a continuing concern.

A random walk polymer model of whole chromosomes was extended to include description of all human chromosomes within a typical cellular volume and to predict the role of DNA loops and attachment points on the spatial distributions of DSB (Ponomarev and Cucinotta, 2006) To overcome the background DSB inherent in experimental methodologies a subtraction technique was formulated and applied to several data sets in collaboration with the Tufts U. NSCOR (PI. L. Hlatky) (Ponomarev et al., 2007). Also these models were used in an imaging approach to study DNA repair foci (Costes et al., 2007) in collaboration with the LBNL NSCOR (PI. M. Barcellos-Hoff). A more detailed model of DNA damage and mutation using Monte-Carlo scoring of energy deposition in atomistic models of DNA and chromosomes is also under development (Nikjoo et al. 2007).

Work on the transmission of specific chromosomal aberrations in subsequent cell cycles was initiated using basic cytogenetic theories. A modeling project to predict the initial yield of terminal and interstitial deletions was begun. Differences between normal cells and specific DNA repair defects are also under study and the role of longer times for open breaks in ATM and MRN deficient cells will be studied to consider the increases in overall and specific types of aberrations and the potential impacts on transmission frequencies.

New statistical models of the probability of SPE frequency and size were developed using our data base of historical SPE and solar cycles (Kim et al., 2006, 2007). The model was extended back to the 15th century for the >30 MeV proton fluences using ice-core data on nitrate concentrations normalized to modern events as reported by McCracken and collaborators. The time dependence of dose-rate for the 30 largest SPE’s was also evaluated. These studies indicate that acute radiation risks will only occur with a realistic probability under EVA conditions, and therefore the focus of acute risk models should be on the so-called prodromal risks (nausea, vomiting, fatigue, etc.) that may occur during EVA in deep-space or on the lunar surface. The DoD based, RIPD model was adapted for a description of risks from SPE. A computer code of the model was developed ab-initio at JSC. This model uses a logistic scale to assign performance degradation probabilities and time-courses for the acute risks. Using the BRYNTRN code and initial estimates of RBEs from the scientific literature, application of the model to the 1972 SPE for EVA conditions was made. (Hu et al., 2007 and in preparation). Work in collaboration with Dr. Smirnova of Moscow State U. was begun to study the probabilities of mortality from one or more, large SPE’s, including the role of an adaptive response due to simulation of granulocytes by a first SPE, leading to protection against a second SPE within the ensuing next few months.

Bibliography Type: Description: (Last Updated: 02/11/2021) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Cucinotta FA, Durante M. "Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings." Lancet Oncol. 2006 May;7(5):431-5. PMID: 16648048 , May-2006
Articles in Peer-reviewed Journals Ponomarev AL, Cucinotta FA. "Chromatin loops are responsible for higher counts of small DNA fragments induced by high-LET radiation, while chromosomal domains do not affect the fragment sizes." Int J Radiat Biol. 2006 Apr;82(4):293-305. PMID: 16690597 , Apr-2006
Articles in Peer-reviewed Journals Kim M-HY, George KA, Cucinotta FA. "Evaluation of skin cancer risks from lunar and Mars missions. " Advances in Space Research 2006;37(9):1798-803. http://dx.doi.org/10.1016/j.asr.2006.03.032 , Aug-2006
Articles in Peer-reviewed Journals Cucinotta FA, Kim M-HY, Ren L. "Evaluating shielding effectiveness for reducing space radiation cancer risks." Radiation Measurements 2006 Oct-Nov;41(9-10):1173-85. http://dx.doi.org/10.1016/j.radmeas.2006.03.011 , Nov-2006
Articles in Peer-reviewed Journals Cucinotta FA, Wilson JW, Saganti P, Hu X, Kim M-HY, Cleghorn T, Zeitlin C, Tripathi RK. "Isotopic dependence of GCR fluence behind shielding." Radiation Measurements 2006 Oct-Nov;41(9-10):1235-49. http://dx.doi.org/10.1016/j.radmeas.2006.03.012 , Nov-2006
Articles in Peer-reviewed Journals Ponomarev AL, Belli M, Hahnfeldt PJ, Hlatky L, Sachs RK, Cucinotta FA. "A robust procedure for removing background damage in assays of radiation-induced DNA fragment distributions." Radiat Res. 2006 Dec;166(6):908-16. PMID: 17149980 , Dec-2006
Articles in Peer-reviewed Journals Cucinotta FA, Kim MH, Schneider SI, Hassler DM. "Description of light ion production cross sections and fluxes on the Mars surface using the QMSFRG model." Radiat Environ Biophys. 2007 Jun;46(2):101-6. PMID: 17342547 , Jun-2007
Articles in Peer-reviewed Journals George K, Cucinotta FA. "The influence of shielding on the biological effectiveness of accelerated particles for the induction of chromosome damage." Advances in Space Research, 2007;39(6):1076-81. http://dx.doi.org/10.1016/j.asr.2007.01.004 , Aug-2007
Articles in Peer-reviewed Journals Costes SV, Ponomarev A, Chen JL, Nguyen D, Cucinotta FA, Barcellos-Hoff MH. "Image-based modeling reveals dynamic redistribution of DNA damage into nuclear sub-domains." PLoS Comput Biol. 2007 Aug;3(8):e155. PMID: 17676951 , Aug-2007
Articles in Peer-reviewed Journals Kim MH, Cucinotta FA, Wilson JW. "A temporal forecast of radiation environments for future space exploration missions." Radiat Environ Biophys. 2007 Jun;46(2):95-100. PMID: 17165049 , Jun-2007
Articles in Peer-reviewed Journals Kim M-HY, Cucinotta FA, Wilson JW. "Mean occurrence frequency and temporal risk analysis of solar particle events." Radiation Measurements 2006 Oct-Nov;41(9-10):1115-22. http://dx.doi.org/10.1016/j.radmeas.2005.11.006 , Nov-2006
Articles in Peer-reviewed Journals Ponomarev AL, Cucinotta FA. "Nuclear fragmentation and the number of particle tracks in tissue." Radiat Prot Dosimetry. 2006;122(1-4):354-61. PMID: 17261538 , Jul-2006
Articles in Peer-reviewed Journals Nikjoo H, Uehara S, Emfietzoglou D, Cucinotta FA. "Track-structure codes in radiation research. A review." Radiation Measurements 2006 Oct-Nov;41(9-10):1052-74. http://dx.doi.org/10.1016/j.radmeas.2006.02.001 , Nov-2006
Project Title:  Space Radiation Risk Assessment Reduce
Fiscal Year: FY 2006 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 06/01/2006  
End Date: 05/31/2011  
Task Last Updated: 10/11/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   Cucinotta, Francis A Ph.D. / University of Nevada, Las Vegas 
Address:  Health Physics & Diagnostic Sciences / BHS-345 
4505 Maryland Parkway 
Las Vegas , NV 89154-3037 
Email: not available 
Phone: (702) 895-4320  
Congressional District:
Web:  
Organization Type: NASA CENTER 
Organization Name: University of Nevada, Las Vegas 
Joint Agency:  
Comments: Formerly at NASA Johnson Space Center, until summer 2013 (Ed., Oct 2013) 
Co-Investigator(s)
Affiliation: 
Pluth, Janice  LBNL 
Cornforth, Michael  U TX Medical Branch 
George, Kerry  Wyle Labs 
Ponomarev, Artem  USRA 
Nikjoo, Hooshang   USRA 
Huff, Janice  USRA 
Kim, Myung-Hee  USRA 
Qualles, Garry  NASA Langley 
Clowdsley, Martha  NASA Langley 
Project Information: 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: Directed Research 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) ARS:Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs)
(2) Cancer:Risk of Radiation Carcinogenesis
(3) CNS:Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure (IRP Rev G)
(4) Degen:Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure (IRP Rev F)
Human Research Program Gaps: (1) Acute02:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict acute radiation risks in astronauts? How can human epidemiology data best support these procedures or models?
(2) Acute06:What are the most effective shielding approaches to mitigate acute radiation risks, how do we know, and implement?
(3) Acute08:How can Probabilistic risk assessment be applied to SPE risk evaluations for EVA, and combined EVA+IVA exposures?
(4) Cancer03:How can experimental models of carcinogenesis be applied to reduce the uncertainties in radiation quality effects from SPEs and GCR, including effects on tumor spectrum, burden, latency and progression (e.g., tumor aggression and metastatic potential)? (IRP Rev F)
(5) Cancer04:How can models of cancer risk be applied to reduce the uncertainties in dose-rate dependence of risks from SPEs and GCR?
(6) Cancer05:How can models of cancer risk be applied to reduce the uncertainties in individual radiation sensitivity including genetic and epigenetic factors from SPE and GCR?
(7) Cancer06:How can models of cancer risk be applied to reduce the uncertainties in the age and gender dependence of cancer risks from SPEs and GCR?
(8) Cancer07:How can systems biology approaches be used to integrate research on the molecular, cellular, and tissue mechanisms of radiation damage to improve the prediction of the risk of cancer and to evaluate the effectiveness of CMs? How can epidemiology data and scaling factors support this approach?
(9) Cancer11:What are the most effective shielding approaches to mitigate cancer risks?
(10) Cancer12:What quantitative models, numerical methods, and experimental data are needed to accurately describe the primary space radiation environment and transport through spacecraft materials and tissue to evaluate dose composition in critical organs for mission relevant radiation environments (ISS, Free-space, Lunar, or Mars)? (IRP Rev F)
(11) CBS-CNS-5:How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE? (IRP Rev F)
(12) CNS06:How can new knowledge and data from molecular, cellular, tissue and animal models of late CNS risks or clinical human data be used to estimate late CNS risks to astronauts from GCR and SPE?
(13) Degen05:What quantitative procedures or theoretical models are needed to extrapolate molecular, cellular, or animal results to predict degenerative tissue risks in astronauts? How can human epidemiology data best support these procedures or models?
Task Description: The Risk Assessment Project at Johnson Space Center is responsible for the integration of results from NASA space radiobiology research into computational models used for astronaut radiation risk assessments. The purpose of the Project is fourfold: (1) evaluate the extent to which ongoing research leads to reduction in the uncertainty of risk assessments and provide, as a metric of program progress, the number of days in space during which the radiation exposure of astronauts remains below NASA limits within a 95% confidence interval (“safe days in space”); (2) perform mission planning studies to predict the number of safe days for any mission; (3) assess the radiation risk to astronauts for ongoing missions in real time; and, (4) provide recommendations for research directions most likely to reduce risk or improve the accuracy of risk predictions. The four categories of risks from radiation in space are defined by the NASA Bioastronautics Roadmap (BR). They are: 1) Carcinogenesis, 2) Acute and late effects to the Central Nervous System (CNS), 3) Degenerative Tissue Effects such as heart disease and cataracts, and 4) Acute Radiation risks. The number of safe days currently predicted for an astronaut’s career is less than required by mission planning, due to the large uncertainties in risk prediction. In particular, a projection uncertainty below + or - 50% is the goal for the 1000-day Mars mission because the high level of risk will require high precision risk evaluations. The current approach used to project risk is based on epidemiology data and on phenomenological models used to derive risk prediction from them. This approach cannot lead to improvements in the accuracy of risk prediction beyond a factor of approximately 2. New approaches using molecular biology and genetics are the only viable ones for achieving the level of accuracy required by space exploration and a robust program to obtain the required data is supported by the Space Radiation Program. However, how to incorporate these data into risk prediction and assessment models is not well understood. This Project Plan describes the approaches that will be used to develop models of risk assessment based on mechanistic space radiobiology research funded by the Space Radiation Program, leading to incremental uncertainty reduction based on new experimental data, and to the development of application software to be used in the NASA operational radiation protection program. To accomplish these goals, we will establish new molecular based models of risk. The molecular pathways that are the hallmarks of genomic instability and cancer, and the perturbation of these pathways by radiation will be described using systems biology approaches and Monte-Carlo simulation. We will develop descriptive models of such pathways utilizing track structure models of biomolecular damage, and deterministic and stochastic kinetic models of dominant molecular pathways causative of BR radiation risks. These simulations will make maximum use of results from mechanistic space radiobiology, and will replace traditional hazard functions and their inherent uncertainties due to reliance on epidemiological or phenomenological approaches.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2006 
Task Progress: New task for FY2006.

Bibliography Type: Description: (Last Updated: 02/11/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2006