Charged Particle Irradiation Research Articles

Energetic Radiation From Galactic Cosmic Ray Interactions With Saturn's Main Rings.

Saturn's main rings have an energetic particle and gamma ray photon radiation environment produced by ring interactions of galactic cosmic ray (GCR) protons and heavier ions penetrating the planetary dipolar magnetic field. Accurate models of this radiation environment are important for interpretation of Pioneer 11 and Cassini in situ measurements near the rings and for constraints on radiolytic contributions to neutral gas production and ice chemistry. A GEANT (GEometry ANd Tracking) based simulation is used to model flux spectra of protons, electrons, positrons, charged pions, neutrons, and gamma ray photons emitted from GCR interactions with H2O ice spheres approximating the ring material. Dependent on location in the A to D rings within the planetary magnetic field of Saturn, only GCR protons above respective energies of 20 to 72 GeV can reach the rings without being deflected away by the magnetic field. Calculated differential and integral fluxes from our simulations have good agreement with in situ Pioneer-11 measurements in selected energy channels. The charged particle and neutral radiation measurements are sensitive, respectively, to the sizes and areal mass densities of ring bodies. Computed gamma ray emission fluxes are 8% of our calculated limit for detection from the Earth by the Fermi Large Area Telescope. Addition of charged particle sensors and neutron-photon imaging spectrometers to a future Saturn Ring Observer mission would provide valuable information on the ring mass structure. The present paper provides a foundation for modeling of Pioneer 11 and Cassini radiation measurements across the main rings and future measurements of radiation from the rings.

Passive charged-particle radiation detection using pn junction in a diamond semiconductor

Utilization of a new pn junction in a high-purity diamond semiconductor enables high-fidelity detection of alpha particles under zero bias voltage, which is possible due to the high built-in electric field.

DNA Repair Deficient Chinese Hamster Ovary Cells Exhibiting Differential Sensitivity to Charged Particle Radiation under Aerobic and Hypoxic Conditions

It has been well established that hypoxia significantly increases both cellular and tumor resistance to ionizing radiation. Hypoxia associated radiation resistance has been known for some time but there has been limited success in sensitizing cells to radiation under hypoxic conditions. These studies show that, when irradiated with low linear energy transfer (LET) gamma-rays, poly (ADP-ribose), polymerase (PARP), Fanconi Anemia (FANC), and mutant Chinese Hamster Ovary (CHO) cells respond similarly to the non-homologous end joining (NHEJ) and the homologous recombination (HR) repair mutant CHO cells. Comparable results were observed in cells exposed to 13 keV/μm carbon ions. However, when irradiated with higher LET spread out Bragg peak (SOBP) carbon ions, we observed a decrease in the oxygen enhancement ratio (OER) in all the DNA of repair mutant cell lines. Interestingly, PARP mutant cells were observed as having the largest decrease in OER. Finally, these studies show a significant increase in the relative biological effectiveness (RBE) of high LET SOBP carbon and iron ions in HR and PARP mutants. There was also an increase in the RBE of NHEJ mutants when irradiated to SOBP carbon and iron ions. However, this increase was lower than in other mutant cell lines. These findings indicate that high LET radiation produces unique types of DNA damage under hypoxic conditions and PARP and HR repair pathways play a role in repairing this damage.

Abstract 5057: Exposure to highly energetic charged (hze) particle radiation is associated with higher colitis and colorectal cancer incidence in IL10-/- mice

Abstract Epidemiological data from atom-bomb survivors and from radiotherapy patients have highlight an underlying risk of colitis and colorectal cancer (CRC) after ionizing radiation-exposure. In contrast, astronauts planning to undertake deep space exploration such as mission to Mars have risk of radiation exposure from highly energetic charged (HZE) particles present in galactic cosmic radiation (GCR) and risk of colitis and CRC after HZE-exposure is yet to be determined. Therefore, animal studies are warranted to address existing uncertainties in colitis and CRC risk prediction after exposure to HZE radiation. Here we report IL10-/- mice as a suitable mouse model for assessment of colitis and CRC risk after exposure to space radiation. Male mice (n=12 mice/group) were whole-body exposed to sham-radiation, γ-rays and 28Si-ion (300 MeV/n; 70 keV/μm; 1.4 Gy). Mice were sacrificed three months after irradiation, and colon swiss-rolls sections were analyzed for colitis and CRC grade was noted in hematoxylin and eosin stained sections. Immunohistochemistry (β-catenin, Cyclin-D1, phospho-H3, iNOS, phoshoNfKβ-p65, and Cox2) was also performed to assess HZE-induced proliferative and inflammatory signaling. Further, inflammation-associated gene-expression analysis was also conducted in both radiation-induced tumor and adjoining normal tissue area. Here we report that relative to controls and γ-ray, colitis score, colon tumor incidence, size and grade was significantly higher after space (28Si-ion) radiation exposure. Higher number of phospho-H3 positive cells in 28Si-ion exposed mouse colon demonstrated increased proliferative index and in increased colon tumors of higher grade, could be due to greater activation of β-catenin and its downstream effector cyclin D1. In addition, higher accumulation of iNOS, phoshoNfKβ-p65, and Cox2 in stromal and epithelial cells after space radiation exposure clearly indicates upregulation of both immune and epithelial inflammation as drivers of colitis and CRC development. Inflammation associated protein markers and gene expression signatures were more pronounced after 28Si-ion exposure. Significant up-regulation of GATA4, ICAM1, ITGA2 and EGFR were exclusive to 28Si-ion exposed mouse colon, however PTGES and TGFβ1 were upregulated in both γ and 28Si-ion exposed mice. Overall, this study suggests that IL10-/- mouse are a suitable model to assess IR-induced colitis and CRC risk, and that space radiation carries higher risk of colitis and CRC incidence, relative to γ-rays at comparable doses. This study has implications for risk prediction in astronauts planning for deep space mission and also for cancer patients planning to undergo particle radiotherapy. Citation Format: Shubhankar Suman, Bo-Hyun Moon, Albert J. Fornace, Kamal Datta. Exposure to highly energetic charged (hze) particle radiation is associated with higher colitis and colorectal cancer incidence in IL10-/- mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5057.

Application of Crystal Elements for Charged Particle Beam Steering and Radiation Beam Generation on the U-70 Synchrotron

Works on the formation of particle and radiation beams using particle channeling and reflection in oriented crystals have been carried out at IHEP over a number of years. Comprehensive theoretical and experimental studies have led to the creation of actually operating systems on the U-70 accelerator. In particular, a slow proton beam extraction with unprecedentedly high parameters, an extraction efficiency of about 85% at a beam intensity of 1012 particles per cycle, has been realized on U-70 using particle channeling in short bent crystals. Experiments to implement the method of particle reflection in crystals for beam extraction and collimation have been carried out on U-70. At present, crystal elements are used in regular U-70 runs and provide half of the particle beams for physical experiments. We summarize the results of this unique experience in the world practice of accelerators and outline its prospects.

Transition Radiation of Charged Particle in the Modulated Anisotropic Magnetodielectric Filling of the Waveguide

Transition Radiation of Charged Particle in the Modulated Anisotropic Magnetodielectric Filling of the Waveguide

Comparing Photon and Charged Particle Therapy Using DNA Damage Biomarkers.

Treatment modalities for cancer radiation therapy have become increasingly diversified given the growing number of facilities providing proton and carbon-ion therapy in addition to the more historically accepted photon therapy. An understanding of high-LET radiobiology is critical for optimization of charged particle radiation therapy and potential DNA damage response. In this review, we present a comprehensive summary and comparison of these types of therapy monitored primarily by using DNA damage biomarkers. We focus on their relative profiles of dose distribution and mechanisms of action from the level of nucleic acid to tumor cell death.

Advantages and Limitations in the Use of Combination Therapies with Charged Particle Radiation Therapy.

Studies are currently underway to help provide basic and clinical evidence for combination particle beam radiation therapy, on which there are few published reports. The purpose of this article is to summarize the current status in the use of particle beams combined with other modalities. Following from experiences in x-ray radiation therapy, combination therapy with proton beams (PBT) has been attempted, and several clinical studies have reported improved survival rates for patients with non-small cell lung cancer, pancreatic cancers, esophageal cancers, and glioblastomas. Recently, basic studies combining PBT with PARP inhibitors and histone deacetylase inhibitors have also reported promising results. In the area of carbon ion therapy (CIT), there are few clinical reports on combination therapy; however, the number of basic research reports exceeds that for PBT. So far, the combined use of cytotoxic drugs with CIT yields independent additive effects. In addition, it is notable that combination therapy with CIT is effective against radioresistant cancer stem-like cells. Recent evidence also suggests that local radiation therapy can induce an effective antitumor immune response. There has been an increased use of combination immune-modulating agents and cytokines with particle beams, especially CIT. The field of radiation therapy is evolving from a strong reliance on local-regional treatment to a growing reliance on systemic immunotherapy. The combined use of anticancer agents with particle radiation therapy has a considerable potential effect. Future research in molecular targeting therapy and immunotherapy may help identify the most efficacious approach for combination therapy with protons and carbon ions.

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.

Alpha particle irradiation of bulk and exfoliated MoS2 and WS2 membranes

The properties of two-dimensional transition metal dichalcogenide (TMDC) nanosheets have been intensively studied in recent years as these compounds have emerged as promising materials for future electronic, photonic and sensor applications. Some of these applications may require the nanosheets to be exposed to radiation fields; therefore, an understanding of their interaction mechanisms with ionising radiation is required.In our experiment, we administer 1.66 MeV helium nuclei to bulk and liquid phase exfoliated MoS2 and WS2 membranes to two total absorbed doses. Raman spectroscopy shows small changes, within the spectrometer resolution, in all samples. Although small, some reproducible changes are observed such as a blueshift of the E2g1 and A1g modes in the bulk MoS2 membrane irradiated to a high total absorbed dose; these shifts are accompanied by a small broadening of both peaks. In bulk WS2 membranes, He2+ irradiation induces a blueshift and monotonic mean peak width decrease of the 2LA(M) phonon mode with increasing fluence. The structural changes associated to these peak shifts are currently unknown. Raman spectroscopy, in agreement with energy dispersive x-ray spectroscopy, shows that amorphous carbon is present in the exfoliated MoS2 and WS2 membranes after irradiation. It is suggested that this amorphous carbon could be formed by radiolytic amorphisation of residual solvent, retained within the ripplocations of the exfoliated nanosheets.Due to the morphology of the liquid phase exfoliated nanosheets, they exhibit greater radiation stability than bulk TMDCs when exposed to heavy charged particle radiation. These results differ from those previously reported for monolayer and bulk MoS2 produced by mechanical exfoliation. The relative radiation stability of the liquid phase exfoliated nanosheets is expected to arise from attenuation and dissipation of the ion beam energy by the residual solvent and the amorphous carbon subsequently produced.

TEM characterization of irradiated microstructure of Fe-9%Cr ODS and ferritic-martensitic alloys

The objective of this study is to evaluate the effects of irradiation dose and dose rate on defect cluster (i.e. dislocation loops and voids) evolution in a model Fe-9%Cr oxide dispersion strengthened steel and commercial ferritic-martensitic steels HCM12A and HT9. Complimentary irradiations using Fe2+ ions, protons, or neutrons to doses ranging from 1 to 100 displacements per atom (dpa) at 500 °C are conducted on each alloy. The irradiated microstructures are characterized using transmission electron microscopy (TEM). Dislocation loops exhibit limited growth after 1 dpa upon Fe2+ and proton irradiation, while any voids observed are small and sparse. The average size and number density of loops are statistically invariant between Fe2+, proton, and neutron irradiated specimens at otherwise fixed irradiation conditions of ∼3 dpa, 500 °C. Therefore, we conclude that higher dose rate charged particle irradiations can reproduce the neutron irradiated loop microstructure with temperature shift governed by the invariance theory; this temperature shift is ∼0 °C for the high sink strength alloys studied herein.

Targeting DNA repair with PNKP inhibition sensitizes radioresistant prostate cancer cells to high LET radiation.

High linear energy transfer (LET) radiation or heavy ion such as carbon ion radiation is used as a method for advanced radiotherapy in the treatment of cancer. It has many advantages over the conventional photon based radiotherapy using Co-60 gamma or high energy X-rays from a Linear Accelerator. However, charged particle therapy is very costly. One way to reduce the cost as well as irradiation effects on normal cells is to reduce the dose of radiation by enhancing the radiation sensitivity through the use of a radiomodulator. PNKP (polynucleotide kinase/phosphatase) is an enzyme which plays important role in the non-homologous end joining (NHEJ) DNA repair pathway. It is expected that inhibition of PNKP activity may enhance the efficacy of the charged particle irradiation in the radioresistant prostate cancer cell line PC-3. To test this hypothesis, we investigated cellular radiosensitivity by clonogenic cell survival assay in PC-3 cells.12Carbon ion beam of62 MeVenergy (equivalent 5.16 MeV/nucleon) and with an entrance LET of 287 kev/μm was used for the present study. Apoptotic parameters such as nuclear fragmentation and caspase-3 activity were measured by DAPI staining, nuclear ladder assay and colorimetric caspase-3method. Cell cycle arrest was determined by FACS analysis. Cell death was enhanced when carbon ion irradiation is combined with PNKPi (PNKP inhibitor) to treat cells as compared to that seen for PNKPi untreated cells. A low concentration (10μM) of PNKPi effectively radiosensitized the PC-3 cells in terms of reduction of dose in achieving the same survival fraction. PC-3 cells underwent significant apoptosis and cell cycle arrest too was enhanced at G2/M phase when carbon ion irradiation was combined with PNKPi treatment. Our findings suggest that combined treatment of carbon ion irradiation and PNKP inhibition could enhance cellular radiosensitivity in a radioresistant prostate cancer cell line PC-3. The synergistic effect of PNKPi and carbon ion irradiation could be used as a promising method for carbon-ion therapy in radioresistant cells.

Single event transients monitoring and diagnostic in FPGA

Analysis of single event transients (SETs) generated in field programmable gate arrays (FPGA) under heavy charged particles (HCP) irradiation and SET suppression methods is performed. The circuit for FPGA SET detection is designed for transients generated both inside FPGA and outside at package pin level. SET registration inside FPGA is carried out as an event when logical cell is switched. The SET control schematic circuit efficiency has been comparatively verified using heavy ion accelerator and picosecond focused laser source. SET in FPGA experimental results are presented and discussed.

Channeling in Bent Crystallites: A New Method to Enhance the Radiation Shielding Efficiency*

A new method is proposed here aiming at designing a shielding wall with the efficiency significantly higher than that of traditional designs. This new design arises from the idea of using channeling in multilayered shielding wall structure, each layer composed of bent crystallites distributed in a way that each layer covers a small section of 2π angular range of which wall is exposed. Part of the incident charged particles will get channeled in bent crystallites in each layer. Bending of channeled particles in bent crystallites will change their directions in the wall increasing their path lengths in the wall which would enhance its shielding efficiency for charged particle radiations. Proposed design is useful for radiation shielding in fission power plants, future fusion reactors and air travel.

Charged particles radiation measurements with Liulin-MO dosimeter of FREND instrument aboard ExoMars Trace Gas Orbiter during the transit and in high elliptic Mars orbit

ExoMars is a joint ESA—Rosscosmos program for investigating Mars. Two missions are foreseen within this program: one consisting of the Trace Gas Orbiter (TGO), that carries scientific instruments for the detection of trace gases in the Martian atmosphere and for the location of their source regions, plus an Entry, Descent and landing demonstrator Module (EDM), launched on March 14, 2016; and the other, featuring a rover and a surface platform, with a launch date of 2020. On October 19, 2016 TGO was inserted into high elliptic Mars’ orbit. The dosimetric telescope Liulin-MO for measuring the radiation environment onboard the ExoMars 2016 TGO is a module of the Fine Resolution Epithermal Neutron Detector (FREND). Here we present first results from measurements of the charged particle fluxes, dose rates, Linear Energy Transfer (LET) spectra and estimation of dose equivalent rates in the interplanetary space during the cruise of TGO to Mars and first results from dosimetric measurements in high elliptic Mars’ orbit. A comparison is made with the dose rates obtained by RAD instrument onboard Mars Science Laboratory during the cruise to Mars in 2011–2012 and with the Galactic Cosmic Rays (GCR) count rates provided by other particle detectors currently in space. The average measured dose rate in Si from GCR during the transit to Mars for the period April 22–September 15, 2016 is 372 ± 37 µGy d−1 and 390 ± 39 µGy d−1 in two perpendicular directions. The dose equivalent rate from GCR for the same time period is about 2 ± 0.3 mSv d−1. This is in good agreement with RAD results for radiation dose rate in Si from GCR in the interplanetary space, taking into account the different solar activity during the measurements of both instruments. About 10% increase of the dose rate, and 15% increase of the dose equivalent rate for 10.5 months flight is observed. It is due to the increase of Liulin-MO particle fluxes for that period and corresponds to the overall GCR intensity increase during the declining phase of the solar activity. Data show that during the cruise to Mars and back (6 months in each direction), taken during the declining of solar activity, the crewmembers of future manned flights to Mars will accumulate at least 60% of the total dose limit for the cosmonaut's/astronaut's career in case their shielding conditions are close to the average shielding of Liulin-MO detectors—about 10 g cm−2. The dosimetric measurements in high elliptic Mars’ orbit demonstrate strong dependence of the GCR fluxes near the TGO pericenter on satellite's field of view shadowed by Mars.

Low doses of oxygen ion irradiation cause long-term damage to bone marrow hematopoietic progenitor and stem cells in mice.

During deep space missions, astronauts will be exposed to low doses of charged particle irradiation. The long-term health effects of these exposures are largely unknown. We previously showed that low doses of oxygen ion (16O) irradiation induced acute damage to the hematopoietic system, including hematopoietic progenitor and stem cells in a mouse model. However, the chronic effects of low dose 16O irradiation remain undefined. In the current study, we investigated the long-term effects of low dose 16O irradiation on the mouse hematopoietic system. Male C57BL/6J mice were exposed to 0.05 Gy, 0.1 Gy, 0.25 Gy and 1.0 Gy whole body 16O (600 MeV/n) irradiation. The effects of 16O irradiation on bone marrow (BM) hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) were examined three months after the exposure. The results showed that the frequencies and numbers of BM HPCs and HSCs were significantly reduced in 0.1 Gy, 0.25 Gy and 1.0 Gy irradiated mice compared to 0.05 Gy irradiated and non-irradiated mice. Exposure of mice to low dose 16O irradiation also significantly reduced the clongenic function of BM HPCs determined by the colony-forming unit assay. The functional defect of irradiated HSCs was detected by cobblestone area-forming cell assay after exposure of mice to 0.1 Gy, 0.25 Gy and 1.0 Gy of 16O irradiation, while it was not seen at three months after 0.5 Gy and 1.0 Gy of γ-ray irradiation. These adverse effects of 16O irradiation on HSCs coincided with an increased intracellular production of reactive oxygen species (ROS). However, there were comparable levels of cellular apoptosis and DNA damage between irradiated and non-irradiated HPCs and HSCs. These data suggest that exposure to low doses of 16O irradiation induces long-term hematopoietic injury, primarily via increased ROS production in HSCs.

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.

The heavy metal oxide glasses within the WO3-MoO3-TeO2 system to investigate the shielding properties of radiation applications

A new series of heavy metal oxide (HMO) glasses in the 10WO3-xMoO3-(90-x)TeO2, x = 10–40 mol% system have been developed using melt quenching technique to investigate their potentiality for radiation shielding applications. Gamma attenuation parameters such as mass attenuation coefficient (MAC) and half value layer (HVL) were measured in a good transmission geometry. The MACs were then used to calculate effective atomic number (Zeff). A HPGe detector was used to detect gamma rays of energies 81 keV, 276 keV, 303 keV, 356 keV and 384 keV emitted through a 133Ba radioactive source. MACs, HVLs and Zeffs were also calculated in a continuous energy region. One more relevant gamma shielding parameter, the buildup factor was also estimated for the glass samples in a continuous energy region at different penetration depths. Moreover, the developed glasses were investigated with respect to their shielding ability against fast neutron and charged particle radiation in the light of the calculated ranges for electron, proton and alpha particle interactions and macroscopic removal cross sections for fast neutrons. The results were compared with ordinary concrete and a lead (Pb) based glass sample wherever possible. It was concluded that the 10WO3-10MoO3-80TeO2 glass sample showed excellent shielding properties when compared to other glasses as well as concrete and Pb-based shielding glass.

Radiation-Induced Bone Toxicity

Normal bone is commonly irradiated during radiation therapy (RT). The true impact of focal radiation on bone tissue remains unclear. The goal of this paper is to present the current understanding of radiation effects on the bone as it pertains to clinically observed radiation side effects. An increased risk of local fracture has been associated with RT-induced bone loss in the pelvis, vertebrae, and ribs. This bone loss appears to occur early after and/or during treatment, which suggests that reactive remodeling of the bone via osteoclast activity is a primary contributor to bone loss and fractures. Several reports have quantified the structural and histological changes observed after bone irradiation. These include changes in bone density and cortical thickness, as well as alterations in both the number and activity of the cells responsible for bone turnover that arise from hematopoietic and mesenchymal lineages: namely, osteoclasts and osteoblasts. All of these changes likely play an important role in the increased risk of fracture reported with RT. However, more research is needed to fully understand the mechanisms of bone damage and its relationship to modifiable factors such as beam energy, dose, photon or charged particle radiation, linear energy transfer (LET), fractionation, and field size.

High Linear Energy Transfer Particle Irradiation Leads to Increased Expression of In Vitro Markers of Immunogenic Cell Death

Radiotherapy (RT) fosters a form of tumor cell death that results in dendritic cell activation, effector T-cell cross priming/tumor trafficking, and the formation of a tumor cell/T-cell immune response. This type of immunogenicity is comprised of the release of immune modulating signals, which include the release of high mobility group box 1 (HMGB1), ATP, and the translocation of calreticulin to the cell surface. Previous studies have demonstrated a positive correlation between markers of immunogenic cell death (ICD) and radiation dose with X-rays. Less is known about the effect of higher energies using charged particle irradiation and ICD. In this study, we explore whether varying linear energy transfer (LET) greater than 60 keV/μm with helium ion irradiation would impact immunogenicity in tumor cells as measured by levels of calreticulin translocation, ATP release, and HMGB1 release. Reporter cell lines designed to detect ATP luminescence (RLUs), red fluorescence protein tagged HMGB1 (relative fluorescent units [RFUs]), and cell surface calreticulin (percentage of calreticulin positive cells [%CRT+]) were derived from TSA (murine mammary carcinoma; syngeneic to BALB/c mice) cells. Prior to irradiation, the cells were seeded on six micron thick Mylar attached to 1.5 cm metal rings. The cells were then irradiated at the Radiological Research Accelerator Facility (RARAF) through a Track Segment Charged-Particle Irradiator. ATP and HMGB1 levels were measured 72 hours after RT and calreticulin was measured 24 hours after RT. Various doses of 250kV X-rays and LETs of helium ions were delivered and levels of these tumor ICD markers were determined. For ATP measurements, when compared to non-irradiated controls, cells irradiated with 5 and 20 Gy X-rays and with 5 Gy 65, 80, 110, and 160 keV/μm helium ions resulted in RLU fold-changes of 1.00 ± 0.05 (non-irradiated), 2.33 ± 0.08, 3.27 ± 0.19, 3.24 ± 0.10, 3.99 ± 0.33, 4.12 ± 0.32, and 2.91 ± 0.16 respectively. For HMGB1 measurements, when compared to controls, cells irradiated with 5 and 20 Gy X-rays and with 5 Gy 65, 80, 110, and 160 keV/μm helium ions resulted in RFU fold-changes of 1.00 ± 0.02 (non-irradiated), 1.43 ± 0.03, 1.72 ± 0.03, 1.97 ± 0.06, 1.64 ± 0.03, 1.61 ± 0.04, and 1.51 ± 0.03, respectively. For calreticulin measurements, when compared to controls, cells irradiated with 5 and 20 Gy X-rays and with 5 Gy 65, 80, 110, and 160 keV/μm helium ions resulted in %CRT+ fold-changes of 1.00 ± 0.12 (non-irradiated), 2.32 ± 0.15, 3.07 ± 0.32, 3.16 ± 0.17, 3.01 ± 0.12, 2.74 ± 0.39, and 1.61 ± 0.15, respectively. Immunogenicity of tumor cells as measured by immune cell death signals increases with high LET ion irradiation when compared to low LET X-ray irradiation at the same dose. These marker levels appear to decrease at LETs greater than 110 keV/μm. Further investigation is warranted on the effects of high LET charged particle irradiation on the tumor immune response.