NASA Space Radiation Research Articles

Late Effects of 16O-Particle Radiation on Female Social and Cognitive Behavior and Hippocampal Physiology

The radiation environment in space remains a major concern for manned space exploration, as there is currently no shielding material capable of fully protecting flight crews. Additionally, there is growing concern for the social and cognitive welfare of astronauts, due to prolonged radiation exposure and confinement they will experience on a mission to Mars. In this artice, we report on the late effects of 16O-particle radiation on social and cognitive behavior and neuronal morphology in the hippocampus of adult female mice. Six-month-old mice received 16O-particle whole-body irradiation at doses of either 0.25 or 0.1 Gy (600 MeV/n; 18-33 cGy/min) at the NASA's Space Radiation Laboratory in Upton, NY. At nine months postirradiation, the animals underwent behavioral testing in the three-chamber sociability, novel object recognition and Y-maze paradigms. Exposure to 0.1 or 0.25 Gy 16O significantly impaired object memory, a 0.25 Gy dose impaired social novelty learning, but neither dosage impaired short-term spatial memory. We observed significant decreases in mushroom spine density and dendrite morphology in the dentate gyrus, cornu ammonis 3, 2 and 1 of the hippocampus, which are critical areas for object novelty and sociability processing. Our data suggest exposure to 16O modulates hippocampal pyramidal and granular neurons and induces behavioral deficits at a time point of nine months after exposure in females.

∆E/∆E Measurements of Energetic Ions Using CVD Diamond Detectors

Experimental and computational results of a ΔE/ΔE diamond detection system are presented. The ΔE/ΔE detection system was evaluated using energetic proton and iron beams striking thick polyethylene targets at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The measured data for diamond sensor A show good agreement with the Geant4 simulation. In addition, simulations have demonstrated the ability to identify hydrogen isotopes using a diamond detection system.

Late effects of 1H irradiation on hippocampal physiology

NASA’s Missions to Mars and beyond will expose flight crews to potentially dangerous levels of charged-particle radiation. Of all charged nuclei, 1H is the most abundant charged particle in both the galactic cosmic ray (GCR) and solar particle event (SPE) spectra. There are currently no functional spacecraft shielding materials that are able to mitigate the charged-particle radiation encountered in space. Recent studies have demonstrated cognitive injuries due to high-dose 1H exposures in rodents. Our study investigated the effects of 1H irradiation on neuronal morphology in the hippocampus of adult male mice. 6-month-old mice received whole-body exposure to 1H at 0.5 and 1 Gy (150 MeV/n; 0.35–0.55 Gy/min) at NASA's Space Radiation Laboratory in Upton, NY. At 9-months post-irradiation, we tested each animal's open-field exploratory performance. After sacrifice, we dissected the brains along the midsagittal plane, and then either fixed or dissected further and snap-froze them. Our data showed that exposure to 0.5 Gy or 1 Gy 1H significantly increased animals’ anxiety behavior in open-field testing. Our micromorphometric analyses revealed significant decreases in mushroom spine density and dendrite morphology in the Dentate Gyrus, Cornu Ammonis 3 and 1 of the hippocampus, and lowered expression of synaptic markers. Our data suggest 1H radiation significantly increased exploration anxiety and modulated the dendritic spine and dendrite morphology of hippocampal neurons at a dose of 0.5 or 1 Gy.

SHIELD and HZETRN comparisons of pion production cross sections

A program of comparing American (NASA) and Russian (ROSCOSMOS) space radiation transport codes has recently begun, and the first paper directly comparing the NASA and ROSCOSMOS space radiation transport codes, HZETRN and SHIELD respectively has recently appeared. The present work represents the second time that NASA and ROSCOSMOS calculations have been directly compared, and the focus here is on models of pion production cross sections used in the two transport codes mentioned above. It was found that these models are in overall moderate agreement with each other and with experimental data. Disagreements that were found are discussed.

Age as a factor in the responsiveness of the organism to the disruption of cognitive performance by exposure to HZE particles differing in linear energy transfer

Exposure to particles of high energy and charge (HZE particles) can produce decrements in cognitive performance. A series of experiments exposing rats to different HZE particles was run to evaluate whether the performance decrement was dependent on the age of the subject at the time of irradiation. Fischer 344 rats that were 2-, 11- and 15/16-months of age were exposed to 16O, 48Ti, or 4He particles at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. As previously observed following exposure to 56Fe particles, exposure to the higher LET 48Ti particles produced a disruption of cognitive performance at a lower dose in the older subjects compared to the dose needed to disrupt performance in the younger subjects. There were no age related changes in the dose needed to produce a disruption of cognitive performance following exposure to lower LET 16O or 4He particles. The threshold for the rats exposed to either 16O or 4He particles was similar at all ages. Because the 11- and 15-month old rats are more representative of the age of astronauts (45–55 years old) the present results indicate that particle LET may be a critical factor in estimating the risk of developing a cognitive deficit following exposure to space radiation on exploratory class missions.

Effects of 1H + 16O Charged Particle Irradiation on Short-Term Memory and Hippocampal Physiology in a Murine Model.

Radiation from galactic cosmic rays (GCR) poses a significant health risk for deep-space flight crews. GCR are unique in their extremely high-energy particles. With current spacecraft shielding technology, some of the predominant particles astronauts would be exposed to are 1H + 16O. Radiation has been shown to cause cognitive deficits in mice. The hippocampus plays a key role in memory and cognitive tasks; it receives information from the cortex, undergoes dendritic-dependent processing and then relays information back to the cortex. In this study, we investigated the effects of combined 1H + 16O irradiation on cognition and dendritic structures in the hippocampus of adult male mice three months postirradiation. Six-month-old male C57BL/6 mice were irradiated first with 1H (0.5 Gy, 150 MeV/n) and 1 h later with 16O (0.1 Gy, 600 MeV/n) at the NASA Space Radiation Laboratory (Upton, NY). Three months after irradiation, animals were tested for hippocampus-dependent cognitive performance using the Y-maze. Upon sacrifice, molecular and morphological assessments were performed on hippocampal tissues. During Y-maze testing, the irradiated mice failed to distinguish the novel arm, spending approximately the same amount of time in all three arms during the retention trial relative to sham-treated controls. Irradiated animals also showed changes in expression of glutamate receptor subunits and synaptic density-associated proteins. 1H + 16O radiation compromised dendritic morphology in the cornu ammonis 1 and dentate gyrus within the hippocampus. These data indicate cognitive injuries due to 1H + 16O at three months postirradiation.

High LET Carbon Ion Radiation Therapy in the Treatment of a Primary Mouse Sarcoma Model at the NASA Space Radiation Laboratory

High LET Carbon Ion Radiation Therapy in the Treatment of a Primary Mouse Sarcoma Model at the NASA Space Radiation Laboratory

Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC1638N/+ mice

Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses in excess of permissible limits with implications for colorectal carcinogenesis. Exposure to IR in outer space occurs at low doses and dose rates, and energetic heavy ions due to their high linear energy transfer (high-LET) characteristics remain a major concern for CRC risk in astronauts. Previously, we have demonstrated that intestinal tumorigenesis in a mouse model (APC1638N/+) of human colorectal cancer was significantly higher after exposure to high dose rate energetic heavy ions relative to low-LET γ radiation. The purpose of the current study was to compare intestinal tumorigenesis in APC1638N/+ mice after exposure to energetic heavy ions at high (50cGy/min) and relatively low (0.33cGy/min) dose rate. Male and female mice (6–8 weeks old) were exposed to either 10 or 50cGy of 28Si (energy: 300MeV/n; LET: 70keV/μm) or 56Fe (energy: 1000MeV/n; LET: 148keV/μm) ions at NASA Space Radiation Laboratory in Brookhaven National Laboratory. Mice (n=20 mice/group) were euthanized and intestinal and colon tumor frequency and size were counted 150days after radiation exposure. Intestinal tumorigenesis in male mice exposed to 56Fe was similar for high and low dose rate exposures. Although male mice showed a decreasing trend at low dose rate relative to high dose rate exposures, the differences in tumor frequency between the two types of exposures were not statistically significant after 28Si radiation. In female mice, intestinal tumor frequency was similar for both radiation type and dose rates tested. In both male and female mice intestinal tumor size was not different after high and low dose rate radiation exposures. Colon tumor frequency in male and female mice after high and low dose rate energetic heavy ions was also not significantly different. In conclusion, intestinal and colonic tumor frequency and size was similar irrespective of energetic heavy ion radiation dose rate suggesting that carcinogenic potential of energetic heavy ions is independent of dose rate.

Overview of the NASA space radiation laboratory

The NASA Space Radiation Laboratory (NSRL) is a multidisciplinary center for space radiation research funded by NASA and located at the Brookhaven National Laboratory (BNL), Upton NY. Operational since 2003, the scope of NSRL is to provide ion beams in support of the NASA Humans in Space program in radiobiology, physics and engineering to measure the risk and ameliorate the effect of radiation in space. Recently, it has also been recognized as the only facility in the U.S. currently capable of contributing to heavy ion radiotherapy research. This work contains a general overview of NSRL structure, capabilities and operation.

Validation of electromagnetic and hadronic physical processes in the interaction of a proton beam with matter: A Solar Particle Events case study with an Al slab

In the study of the effectiveness of shielding materials against radiations, one of the main steps concerns with the validation of models describing the interaction processes of the radiation of interest with the material chosen for the shielding. This paper shows the results of the validation of electromagnetic and hadronic processes with the aim to contribute to the study of protection for astronauts against the radiations due to the Solar Particle Events, in particular to the selection of the optimal material for radiation shielding. The physics case deals with the interaction of a proton beam with an aluminum slab about 20g/cm2 thick. Two specific applications, STP and DOSE, were developed by using Geant4 package. STP computes the radiations produced in the interaction and their stopping power; DOSE computes the absorbed dose from the stopping power calculated by STP. The validation process was performed in two steps. In the first one, the output of the STP code is compared to data available on NIST database; in the second one, the absorbed dose computed with DOSE is compared to the dose gathered during an experiment performed at the NASA Space Radiation Laboratory involving the bombardment of an aluminum slab with a 1GeV proton beam. The computing model has allowed us to correlate the size of the impinging beam profile to the dose measured before and after an Al slab. The sharp increase of the dose in the position right after the slab might be due to the stochastic nature of the trajectories of charged ions in matter which makes the radiation to emerge with non-zero transverse linear momentum. From the case examined here, we conclude that aluminum is not an efficient material for Solar Particle Event shielding.

SU‐C‐204‐04: Irradiation of Human Cell Lines Using Various Ions

Purpose:The purpose of this study is to investigate and quantify the biological effects of ion radiation using several human cell lines. We aim to answer the question of whether carbon ion the most ideal ion species for heavy ion radiotherapy.Methods:The cells were irradiated at different positions along the pristine Bragg peak of several ions with different atomic number. The biological effectiveness was evaluated using the clonogenic cell survival assay. Irradiation of three human lung cancer cell lines and a fibroblast cell line were undertaken using the charged particle beam at the NASA Space Radiation Laboratory at Brookhaven National Lab. Four mono‐energetic ion beams (carbon, oxygen, helium and lithium) were used to irradiate the cells. Water or media‐filled T25 flasks were lined up along the beam line so that the cell‐containing surfaces of the flasks were placed at a specific depth along the pristine Bragg curve. Four depths along the curve, representing entrance point, rising peak, peak and distal fall off, were selected to determine biological effectiveness. Gaf‐chromic films were placed between the flasks to monitor the irradiation as soon as it was finished.Results:For all ion radiations, the maximum cell killing effect occurs at either peak or distal fall off, depending on the cell lines. For instance, for the fibroblast cell line AGO1522, RBEs of 1.4, 1.2, 1.4 and 1.9 were observed at the Bragg peak for Helium, Lithium, Carbon and Oxygen ions. Comparing positions, RBEs of 0.9, 1.2, 1.4 and 1.8 were observed for carbon irradiation of AGO‐1522 cells positions corresponding to entrance, rising peak, peak and distal fall off.Conclusion:RBE values differ with position in the Bragg peak, ion species and cell line. Ions other than carbon may prove more effective in certain irradiation conditions and may contribute to optimized heavy ion therapy.

TU‐H‐BRB‐05: Radiation Countermeasures and the NASA Space Radiation Program

The US government has substantial research and development activities underway for medical countermeasures that will insure the long‐term safety and survival of the country's population after unfortunate large‐scale biological, chemical and radiological and nuclear events. Preparedness includes research and development of medical countermeasures to address radiation‐induced cutaneous and internal injury from radiation and nuclear events as well as for minimizing radiation risks incurred during and after travel in space. Other important research and development efforts include the repurposing of countermeasures and development of radioprotectors and mitigators to improve the outcome of radiation treatment. Participating agencies include NIAID, BARDA, NCI, and NASA, with examples of research and development funding that includes the Centers for Medical Countermeasures against Radiation (CMCR) consortia (NIAID) and primary and sub‐contracts with commercial entities (BARDA). Each of these programs requires substantial medical and health physics effort in collaboration with biology colleagues to provide a range of radiation sources, dosimetry instrumentation and assessment methods, and animal models for specific radiation‐induced effects and injuries. Radiation countermeasure activities for government agencies will be reviewed, the importance of model development will be stressed, example radiation countermeasure research projects will be reviewed, and the roles for medical physicists will be discussed. Learning Objectives: Review US national radiation countermeasure activities. Review the roles for medical physicists in radiation countermeasures research and development. Understand specific physics challenges in radiation research that need solutions.Research for JD Bourland supported in part by: NIH/NIAID, U19 AI67798 (subcontract 131714). NIH/NCI, R01CA155293. HHSO10020130019C, BARDA/Argentum Medical LLC.; J. Bourland, Research supported in part by:NIH/NIAID, U19 AI67798 (subcontract 131714); NIH/NCI, R01CA155293; HHSO10020130019C, BARDA/Argentum Medical LLC.; P. Prasanna, Supported by the Radiation Research Program, National Cancer Institute

Use of the NASA Space Radiation Laboratory at Brookhaven National Laboratory to Conduct Charged Particle Radiobiology Studies Relevant to Ion Therapy

Although clinical studies with carbon ions have been conducted successfully in Japan and Europe, the limited radiobiological information about charged particles that are heavier than protons remains a significant impediment to exploiting the full potential of particle therapy. There is growing interest in the U.S. to build a cancer treatment facility that utilizes charged particles heavier than protons. Therefore, it is essential that additional radiobiological knowledge be obtained using state-of-the-art technologies and biological models and end points relevant to clinical outcome. Currently, most such ion radiotherapy-related research is being conducted outside the U.S. This article addresses the substantial contributions to that research that are possible at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), which is the only facility in the U.S. at this time where heavy-ion radiobiology research with the ion species and energies of interest for therapy can be done. Here, we briefly discuss the relevant facilities at NSRL and how selected charged particle biology research gaps could be addressed using those facilities.

Galactic cosmic ray simulation at the NASA Space Radiation Laboratory

Most accelerator-based space radiation experiments have been performed with single ion beams at fixed energies. However, the space radiation environment consists of a wide variety of ion species with a continuous range of energies. Due to recent developments in beam switching technology implemented at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), it is now possible to rapidly switch ion species and energies, allowing for the possibility to more realistically simulate the actual radiation environment found in space. The present paper discusses a variety of issues related to implementation of galactic cosmic ray (GCR) simulation at NSRL, especially for experiments in radiobiology. Advantages and disadvantages of different approaches to developing a GCR simulator are presented. In addition, issues common to both GCR simulation and single beam experiments are compared to issues unique to GCR simulation studies. A set of conclusions is presented as well as a discussion of the technical implementation of GCR simulation.

Reference field specification and preliminary beam selection strategy for accelerator-based GCR simulation

The galactic cosmic ray (GCR) simulator at the NASA Space Radiation Laboratory (NSRL) is intended to deliver the broad spectrum of particles and energies encountered in deep space to biological targets in a controlled laboratory setting. In this work, certain aspects of simulating the GCR environment in the laboratory are discussed. Reference field specification and beam selection strategies at NSRL are the main focus, but the analysis presented herein may be modified for other facilities and possible biological considerations. First, comparisons are made between direct simulation of the external, free space GCR field and simulation of the induced tissue field behind shielding. It is found that upper energy constraints at NSRL limit the ability to simulate the external, free space field directly (i.e. shielding placed in the beam line in front of a biological target and exposed to a free space spectrum). Second, variation in the induced tissue field associated with shielding configuration and solar activity is addressed. It is found that the observed variation is likely within the uncertainty associated with representing any GCR reference field with discrete ion beams in the laboratory, given current facility constraints. A single reference field for deep space missions is subsequently identified. Third, a preliminary approach for selecting beams at NSRL to simulate the designated reference field is presented. This approach is not a final design for the GCR simulator, but rather a single step within a broader design strategy. It is shown that the beam selection methodology is tied directly to the reference environment, allows facility constraints to be incorporated, and may be adjusted to account for additional constraints imposed by biological or animal care considerations. The major biology questions are not addressed herein but are discussed in a companion paper published in the present issue of this journal. Drawbacks of the proposed methodology are discussed and weighed against alternative simulation strategies.

The Effect of High LET Space Radiation on the Human Hematopoietic System: Preliminary Results from the First In Vivo Model

Background: The effects of spaceflight on human physiology are complex and represent a sum of many factors, the main two of which are microgravity and space radiation. The latter is composed of high-energy protons and HZE particles, along with secondary radiation produced in shielding and tissue. One major concern is short- and long-term radiation-induced injury to the hematopoietic system, one of the most radiosensitive tissues in the human body. Previous studies demonstrated functional and/or numerical changes in T and /or B-cells of crewmembers of STS-41B and STS-41D and altered myelopoiesis during STS-63 and STS-69. Although these changes reversed post return, they persisted in space and were more recently documented during a six month mission to the International Space Station. The main goal of NASA's space radiation research program is to enable human space exploration within acceptable risks and to reduce uncertainties regarding risk projections. We present the first ground based in vivo study evaluating the effects of high- and low-LET radiation on the human immune system by using a reconstituted human hematopoietic system in a humanized mouse model. We measure post-radiation depletion and repopulation kinetics, tumor formation and DNA damage.Methods: NSG mice were irradiated with 2Gy of gamma rays and injected 20 hours later with 2x105 CD34+cells isolated from cord blood. After a 12 week engraftment period, peripheral blood flow cytometry with anti-human and anti-mouse antibodies (human and mouse CD45, human CD3 and human CD19) was performed to confirm engraftment (>50% of human cells in moue blood, Figure 1). We irradiated the humanized-NSG mice (hu-NSG) with 0.2 or 0.4 Gy of 350 MeV/n28 Si-ions, which are established components of LET radiation. We measured changes in peripheral blood mononuclear cell counts (huCD45+PBMC) 7 and 30 days post irradiation to assess early effects and recovery kinetics. Multicolor flow cytometric immunophenotyping (FCI) analysis of tissue and blood samples was performed according to standard cell surface staining protocols. Conventional cytogenetic analysis was performed 5 months post radiation on enriched fractions of human HSC and progenitor cells, isolated from marrow of irradiated mice. We performed secondary transplants to transmit the genetic changes imparted by irradiation in the first animal to the secondary host system to allow further monitoring. In addition whole exome and transcriptome sequencing is underway on stem cell and progenitor (lineage negative) pools on a subset of mice.Results: To date 120 well engrafted NSG mice were irradiated with 0.2 or 0.4 Gy of 350 MeV/n28 Si-ions. No decrease versus a mild decrease of huCD45+ PBMCs was observed on day 7 in the 0.2 and 0.4 Gy radiated cohort respectively, with the latter demonstrating full recovery on day 30 compared to normal control mice (Figure 2). No lymphoproliferative or myeloproliferative disorder was noted in 46 irradiated mice using 8 color FCI analyses. Median percentage of peripheral blood mature B-cells, T cells and NK cells was 41%, 36.5% and 9% respectively. Kappa /lambda ratio, CD4/CD8 ratio and NK cell/T cell ratio were 0.9, 3.6, and 0.3 respectively. Bone marrow evaluation demonstrated 0.08% to 0.3% myeloblasts (median: 0.15%) positive for CD34 /CD117/CD33 and HLADR. Moderate monocytosis (CD64+/CD4+/HLA-DR+) was noted, ranging from 39% to 51% (median 47%). Preliminary results of cytogenetic analysis revealed diploid male and female karyotypes without abnormalities in at least 20 metaphases analyzed. Successful secondary transplants were performed in 30 mice. Results of whole exome and transcriptome sequencing are pending.Conclusions: This study shows for first time data on the effects of high -LET space type of radiation on human hematopoietic system in vivo. Preliminary results show that high-LET 350 MeV/n 28 Si radiation has relatively minor effects on peripheral blood cell counts and depletion/recovery kinetics. In addition our preliminary analysis did not demonstrate a leukemogenic effect in the short time period (months) assessed after the irradiation. The study is currently in progress and more data will be available. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Charged Particle Therapy with Mini-Segmented Beams.

One of the fundamental attributes of proton therapy and carbon ion therapy is the ability of these charged particles to spare tissue distal to the targeted tumor. This significantly reduces normal tissue toxicity and has the potential to translate to a wider therapeutic index. Although, in general, particle therapy also reduces dose to the proximal tissues, particularly in the vicinity of the target, dose to the skin and to other very superficial tissues tends to be higher than that of megavoltage x-rays. The methods presented here, namely, “interleaved carbon minibeams” and “radiosurgery with arrays of proton and light ion minibeams,” both utilize beams segmented into arrays of parallel “minibeams” of about 0.3 mm incident-beam size. These minibeam arrays spare tissues, as demonstrated by synchrotron x-ray experiments. An additional feature of particle minibeams is their gradual broadening due to multiple Coulomb scattering as they penetrate tissues. In the case of interleaved carbon minibeams, which do not broaden much, two arrays of planar carbon minibeams that remain parallel at target depth, are aimed at the target from 90° angles and made to “interleave” at the target to produce a solid radiation field within the target. As a result, the surrounding tissues are exposed only to individual carbon minibeam arrays and are therefore spared. The method was used in four-directional geometry at the NASA Space Radiation Laboratory to ablate a 6.5-mm target in a rabbit brain at a single exposure with 40 Gy physical absorbed dose. Contrast-enhanced magnetic resonance imaging and histology 6-month later showed very focal target necrosis with nearly no damage to the surrounding brain. As for minibeams of protons and light ions, for which the minibeam broadening is substantial, measurements at MD Anderson Cancer Center in Houston, TX, USA; and Monte Carlo simulations showed that the broadening minibeams will merge with their neighbors at a certain tissue depth to produce a solid beam to treat the target. The resulting sparing of proximal normal tissue allows radiosurgical ablative treatments with smaller impact on the skin and shallow tissues. This report describes these two methods and discusses their potential clinical applications.

Calcium and lithium ion production for laser ion source.

Calcium and lithium ion beams are required by NASA Space Radiation Laboratory at Brookhaven National Laboratory to simulate the effects of cosmic radiation. To identify the difficulties in providing such highly reactive materials as laser targets, both species were experimentally tested. Plate shaped lithium and calcium targets were fabricated to create ablation plasmas with a 6 ns 1064 nm neodymium-doped yttrium aluminum garnet laser. We found significant oxygen contamination in both the Ca and Li high charge state beams due to the rapid oxidation of the surfaces. A large spot size, low power density laser was used to create low charge state beams without scanning the targets. The low charge state Ca beam did not have any apparent oxygen contamination, showing the potential to clean the target entirely of oxide with a low power beam once in the chamber. The Li target was clearly still oxidizing in the chamber after each low power shot. To measure the rate of oxidation, we shot the low power laser at the target repeatedly at 10 s, 30 s, 60 s, and 120 s interval lengths, showing a linear relation between the interval time and the amount of oxygen in the beam.

Issues for Simulation of Galactic Cosmic Ray Exposures for Radiobiological Research at Ground-Based Accelerators.

For radiobiology research on the health risks of galactic cosmic rays (GCR) ground-based accelerators have been used with mono-energetic beams of single high charge, Z and energy, E (HZE) particles. In this paper, we consider the pros and cons of a GCR reference field at a particle accelerator. At the NASA Space Radiation Laboratory (NSRL), we have proposed a GCR simulator, which implements a new rapid switching mode and higher energy beam extraction to 1.5 GeV/u, in order to integrate multiple ions into a single simulation within hours or longer for chronic exposures. After considering the GCR environment and energy limitations of NSRL, we performed extensive simulation studies using the stochastic transport code, GERMcode (GCR Event Risk Model) to define a GCR reference field using 9 HZE particle beam–energy combinations each with a unique absorber thickness to provide fragmentation and 10 or more energies of proton and 4He beams. The reference field is shown to well represent the charge dependence of GCR dose in several energy bins behind shielding compared to a simulated GCR environment. However, a more significant challenge for space radiobiology research is to consider chronic GCR exposure of up to 3 years in relation to simulations with animal models of human risks. We discuss issues in approaches to map important biological time scales in experimental models using ground-based simulation, with extended exposure of up to a few weeks using chronic or fractionation exposures. A kinetics model of HZE particle hit probabilities suggests that experimental simulations of several weeks will be needed to avoid high fluence rate artifacts, which places limitations on the experiments to be performed. Ultimately risk estimates are limited by theoretical understanding, and focus on improving knowledge of mechanisms and development of experimental models to improve this understanding should remain the highest priority for space radiobiology research.

SU‐E‐T‐526: Irradiation of Human Cell Lines Using Carbon Ions: Real Time Dosimetry Using Gaf‐Chromic Film

Purpose:The purpose of this study is to investigate and quantify several factors affecting biological effects of carbon ions such as cell type, dose, energy and position where the cells are irradiated along the pristine Bragg curve.Methods:Experiments to quantify clonogenic cell survival in three human lung cancer cell lines and a fibroblast cell line were performed at the NASA Space Radiation Laboratory, BNL, Upton, USA. A system of water or media‐filled T25 flasks lined up along the beam axis was designed so that the cell‐containing surfaces of the flasks were placed at specific depths along the Bragg curve. Gaf‐chromic films were placed between the flasks to monitor the dose distribution in the sample as soon as the irradiation was finished. Additional studies were conducted at four selected depths along the Bragg curve to obtain full cell survival dose response curves for the four cell lines.Results:The percent depth dose of the beams was determined using an ionization chamber and showed that the physical Bragg peak is at 22.5 cm water depth. However, the clonogenic cell survival data indicated that the maximum cell killing occurred at 21.5 cm. Gaf‐chromic films revealed some inhomogeneity in the dose distribution on the flasks near the peak, presumably due to lack of scattering from the sides of the flasks, which might account for the differences. Depending on the cell line and radiation dose, the maximum cell killing (i.e., the greatest RBE) is at the 21.5 (the peak) or 24 cm (distal fall off) depth.Conclusion:There is a difference in biological effect along the Bragg curve of a carbon ion beam, indicating an elevated RBE at or beyond the end of the range. Gaf‐chromic films are proven to be effective in monitoring the 2D irradiation pattern to the flasks.Research supported by NIH/NCI through grant no. R21 CA182259.