Heavy Radiation Research Articles

Characterization of charge sharing induced by high LET heavy ions using inverter chains in a commercial bulk FinFET process

The inverter is one of the most important cell types in any standard cell library at each technology node, and it is also very important for single-event research. The distributions and cross-sections of single-event transients (SETs) and single-event multiple transients (SEMTs) were characterized using 14/16 nm bulk fin field-effect transistor (FinFET) inverters under heavy ion radiation. An inverter with double driving strength (INVX2) was used as an instantiate object to observe the SET and SEMT response. 181Ta with energies of 1891 GeV and 2000.5 MeV were used respectively in the experiments, of which the linear energy transfer (LET) values were 87.4 MeV cm2 mg−1 and 75.4 MeV cm2 mg−1. The test results indicated that: (a) the mean pulse widths of the SET and SEMT were less than 100 ps, and decreased with LET decreasing; (b) there was charge sharing between abutted INVX2 inverters placed horizontally, and the generation probability of SEMT induced by charge sharing was less than 1% even if the LET of heavy ion reached 87.4 MeV cm2 mg−1. The results were beneficial for a better understanding of SET and SEMT tolerance for inverters in FinFET technology.

Effects of heavy ions (12C6+) on malignant melanoma B16F10 cells.

BackgroundThis study aimed to investigate the effects of heavy ion (12C6+) irradiation on the proliferation, apoptosis, cell cycle, migration, and epithelial-mesenchymal transition (EMT) of B16F10 cells.MethodsThe B16F10 cells, which is a malignant melanoma cell line widely used in research, irradiated by 12C6+ and X-ray were detected by Hoechst 33342/propidium iodide double staining, Western blot, flow cytometry, and cell scratch tests to evaluate cell proliferation, expression of apoptosis-related proteins, G2/M phase arrest, cell migration, cell invasion and EMT.ResultsCompared with the same physical X-ray dose, 12C6+ could effectively inhibit the proliferation of B16F10 cells, inhibit the expression of B-cell lymphoma-2 (Bcl-2) and cellular-myelocytomatosis viral oncogene (c-Myc), and induce the expression of Bax to promote the apoptosis of B16F10 cells. After 12C6+ irradiation, the B16F10 cells exhibited G2/M phase arrest. B16F10 cells were highly sensitive to 12C6+ irradiation. Moreover, compared with X-ray, the 12C6+ irradiation significantly inhibited the migration of B16F10 cells and inhibited extracellular matrix cleavage, induced E-cadherin expression, enhanced cell adhesion, and further inhibited cell invasion, migration, and EMT.ConclusionsThe B16F10 cells were highly radiosensitive to 12C6+. Compared with X-ray, B16F10 cells irradiated by 12C6+ significantly reduced the expressions of matrix metalloproteinases to inhibit extracellular matrix cleavage and, thus, effectively inhibit cell invasion and metastasis. However, although the issue of the different therapeutic effects of heavy ion and X-ray radiotherapy on malignant melanoma was investigated and preliminary research results were obtained, several problems must be further studied.

Simulation Study of Single-Event Effects for the 4H-SiC VDMOSFET With Ultralow On-Resistance

Silicon carbide (SiC) vertical-diffused metal oxide field transistor (VDMOSFET) is an important power device for aerospace application. However, it is sensitive to heavy particles radiation in space which can cause catastrophic single-event effects (SEEs). In this article, a method of SEE hardening at a high linear energy transfer (LET) value range is studied to the 1.2 kV-rated SiC VDMOSFET by the 2-D numerical simulator SILVACO TCAD. Simulation results illustrate that, compared with the VDMOSFET which only has four buffer (FB-VDMOSFET) layers, the improved MOSFET could increase the abilities of single-event burnout (SEB) and the single-event gate rupture (SEGR) of the device effectively. At the same time, the proposed MOSFET has the lower specific ON-resistance ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${R}_{\text {on, sp}}$ </tex-math></inline-formula> ) at room temperature. As a result, the gate oxide of the FB-VDMOSFET has reached 7.5 MV/cm and the maximum temperature reached 2480 K at a voltage of 600 V and an LET value of 0.5 pC/ <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> . However, the maximum temperature of the improved VDMOSFET is 2150 K when <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${V}_{\mathrm {DS}}$ </tex-math></inline-formula> = 950 V.

Comparative study of RARP and heavy ion radiotherapy sexual functional changes for prostate cancer using the propensity score matching method

ABSTRACT Introduction We mainly perform Robotic-Assisted laparoscopic Radical Prostatectomy (RARP) and Heavy Ion Radiotherapy (HIRT) as curative treatment for prostate cancer. Several factors such as cancer control and quality of life after treatment are considered to be important, but there are few reports comparing sexual function changes before and after treatment between RARP and HIRT. Objective We performed retrospective study comparing the evaluation of sexual function after RARP and HIRT cases using the propensity score matching method. Methods 127 patients treated by RARP from 2014 to 2018 and 190 patients treated by HIRT monotherapy from 2010 to 2019 were evaluated. We evaluated Expanded Prostate Cancer Index Composite (EPIC) score before and after treatment. The EPIC was compared before, 12 months, and 24 months after treatment. Propensity score matching was performed using the age at treatment, PSA value, T stage, and pretreatment EPIC comprehensive score of sexual function as covariates. A cohort of 101 patients in each group was prepared and examined. Results The mean ± standard deviation of each of the RARP and HIRT groups were age; 65.1 ± 5.9, 65.3 ± 6.5 years, PSA value; 6.31 ± 2.07, 6.34 ± 2.46 ng / ml, pretreatment EPIC sexual function overall score; 46.4 ± 15.6, 48.2 ± 16.2. In both groups, T1N0M0 was 16%, T2N0M0 was 83%, and T3N0M0 was 1%. The total EPIC sexual function scores before, 12 months, and 24 months after treatment were 46.4, 27.9, 28.2 in the RARP group, and 48.2, 41.4 in the HIRT group, respectively. In both groups, there was a significant decrease in score after 12 months and 24 months compared to before treatment (p &amp;lt;0.05). At 12 and 24 months, the total EPIC sexual function score in the HIRT group was significantly higher than RARP group (p &amp;lt;0.001). Conclusion In prostate cancer cases adjusted by propensity score matching, the decrease in EPIC sexual function score was significantly smaller in the HIRT group than RARP group. The results of this study seemed to be useful information for decision making with patients. Disclosure Work supported by industry: no.

Role of DNA repair pathways in the recovery of a dried, radioresistant cyanobacterium exposed to high-LET radiation: implications for the habitability of Mars

AbstractIf life ever appeared on Mars and if it did refuge into sub-superficial environments when surface conditions turned too hostile, then it should have been periodically revived from the frozen, dormant state in order to repair the accumulated damage and reset the survival clock to zero for the next dormant phase. Thus, unravelling how long Earth dormant microorganisms can cope with high-LET radiation mimicking long-term irradiation is fundamental to get insights into the long-term resilience of a dormant microbial life in the Martian subsurface over geological timescales that might have taken advantage of periodically clement conditions that allowed the repair of the accumulated DNA damage. The exposure of dried cells of the radioresistant cyanobacterium Chroococcidiopsis sp. CCMEE 029 to 2 kGy of heavy-ion radiation (Fe ions) did not significantly reduce its survival, although DNA damage was accumulated. Upon rehydration, DNA lesions were repaired as suggested by the over-expression of genes involved in the repair of double strand breaks (DSBs), oxidized bases and apurinic-apyrimidinic sites. Indeed, the monitoring of repair genes upon rehydration suggested a key role of the RecF homologous recombination in repairing DSBs. While the fact that out of the eight genes of the BER system, only one was up-regulated, suggested the absence of DNA lesions generally induced by UV radiation. In conclusion, the non-significantly reduced survival of dried Chroococcidiopsis exposed to 2 kGy of Fe-ion radiation further expanded our appreciation of the resilience of a putative dormant life in the Martian subsurface. Moreover, it is also relevant when searching life on Europa and Enceladus where the radiation environment might critically affect the long-term survival of dormant, frozen life forms.

Novel Radiation-Hardened High-Speed DFF Design Based on Redundant Filter and Typical Application Analysis

A cell-level radiation hardening by design (RHBD) method based on commercial processes of single event transient (SET) and single event upset (SEU) is proposed in this paper, in which new radiation-hardened D-type flip-flops (DFFs) are designed. An application-specific integrated circuit (ASIC) of a million gates level is developed based on DFFs, and SEU and single event functional interruption (SEFI) heavy-ion radiation tests are carried out. The experimental results show that the new DFF SEU ability is increased by 63 times compared with the DICE-designed DFF, and is three orders of magnitude higher than the redundantly designed DFF. The SEFI ability of the ASIC designed by the new DFF is 2.6 times higher than the circuit hardened by the TMR design.

Generation of proton and carbon ion beam from laser ion source using hydrocarbon oil target

The supply of high-flux proton and carbon ions are required for applications such as accelerator-driven neutron sources and heavy ion radiotherapy. So far, it is shown that a laser ion sources using the target of plastics made of hydrocarbons can provide protons and carbon ions. On the other hand, due to the damage of the target by laser irradiation, it is necessary to change the laser irradiation position every time, and the number of ion supply is limited to the area of the laser target. To solve the problem of target damage, we suggest a laser target in which the surface is continuously renewed by flowing hydrocarbon oil instead of solid hydrocarbon. In this study, we demonstrated the generation of protons and carbon ions using the target made of a hydrocarbon oil for a diffusion pump.

Concept design of new compact electron cyclotron resonance ion source with permanent magnets for multi-ion radiotherapy

The multi-ion radiotherapy with dose distribution and Liner Energy Transfer optimization is being studied at QST. Helium, carbon, oxygen and neon ions are considered as ion species for multi-ion therapy. A basic experiment using these ion beams has been carried out at the HIMAC. For heavy-ion radiotherapy facility, it is desirable to operate with only one ECR ion source with permanent magnets from the viewpoint of cost and maintenance. We considered the operating method with only one ion source for multi-ion radiotherapy. Ionization gases were helium, methane, oxygen, and neon to produce He2+, C4+, O6+ and Ne7+ ions. Requirement values of beam current were 940 μA correspond to He2+, 290 μA to C4+, 330 μA to O6+, and 245 μA to Ne7+, respectively. This value was obtained from the number of particles required for the cancer treatment and the transmission efficiency of the accelerator in the HIMAC. We performed some beam tests for design of a new compact ion source with the existing 18 GHz ECR ion source (NIRS-HEC). From the results of the beam tests, we estimate the mirror magnetic field of NIRS-HEC by using POISSON/SUPERFISH code. Then, the structure of the permanent magnets for new ECR ion source is determined so that they reproduce the values of the upstream mirror peak (Binj), B minimum (Bmin) and the downstream mirror peak (Bext) at the NIRS-HEC. The magnetic field of Binj, Bmin and Bext at NIRS-HEC were 1.14 T, 0.475 T and 0.9 T, respectively.

Antibiotic-resistant bacteria and antibiotic resistance genes in uranium mine: Distribution and influencing factors

Both heavy metals and radiation could affect the proliferation and dissemination of emerging antibiotic resistance pollutants. As an environmental medium rich in radioactive metals, the profile of antibiotic resistance in uranium mine remains largely unknown. A uranium mine in Guangdong province, China was selected to investigate the distribution and influencing factors of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) including intracellular ARGs (iARGs), adsorbed-extracellular ARGs (aeARGs), and free extracellular ARGs (feARGs). The result indicated that sulfonamide and tetracycline ARB could be generally detected in mining area with the absolute concentrations of 7.70 × 102–5.18 × 105 colony forming unit/g. The abundances of aeARGs in mine soil were significantly higher than those of iARGs (p < 0.05), highlighting the critical contribution of aeARGs to ARGs spread. The feARGs in mine drainage and its receiving river were abundant (3.38 × 104–1.86 × 107 copies/mL). ARB, aeARGs, and iARGs may correlate with nitrogen species and heavy metals (e.g., U and Mn), and feARGs presented a significant correlation with chemical oxygen demand (p < 0.05). These findings demonstrate the occurrence of ARB and ARGs in uranium mine for the first time, thereby contributing to the assessment and control of the ecological risk of antibiotic resistance in radioactive environments.

High turnover and rescue effect of XRCC1 in response to heavy charged particle radiation

The DNA damage response is a highly orchestrated process. The involvement of the DNA damage response factors in DNA damage response depends on their biochemical reactions with each other and with chromatin. Using online live-cell imaging combined with heavy ion microbeam irradiation, we studied the response of the scaffold protein X-ray repair cross-complementary protein 1 (XRCC1) at the localized DNA damage in charged particle irradiated HT1080 cells expressing XRCC1-tagged RFP. The results showed that XRCC1 was recruited to the DNA damage with ultrafast kinetics in a poly ADP-ribose polymerase-dependent manner. The consecutive reaction model well explained the response of XRCC1 at ion hits, and we found that the XRCC1 recruitment was faster and dissociation was slower in the G2 phase than those in the G1 phase. The fractionated irradiation of the same cells resulted in accelerated dissociation at the previous damage sites, and the dissociated XRCC1 immediately recycled with a higher recruitment efficiency. Our data revealed XRCC1’s new rescue mechanism and its high turnover in DNA damage response, which benefits our understanding of the biochemical mechanism in DNA damage response.

Fixed Beamline Optimization for Intensity Modulated Carbon-Ion Therapy.

A major obstacle for the adoption of heavy ion therapy is the cost and technical difficulties to construct and maintain a rotational gantry. Many heavy ion treatment facilities instead choose to construct fixed beamlines as a compromise, which we propose to mitigate with optimized treatment couch angle. We formulate the integrated beam orientation and scanning spot optimization problem as a quadratic cost function with a group sparsity regularization term. The optimization problem is efficiently solved using fast iterative shrinkage-thresholding algorithm (FISTA). To test the method, we created the fixed beamline plans with couch rotation (FBCR) and without couch rotation (FB) for intensity modulated carbon-ion therapy (IMCT) and compared with the ideal scenario where both the couch and gantry have 360 degrees of freedom (GCR). FB, FBCR, and GCR IMCT plans were compared for ten pancreas cases. The FBCR plans show comparable PTV coverage and OAR doses for each pancreas case. In conclusion, the dosimetric limitation of fixed beams in heavy ion radiotherapy may be largely mitigated with integrated beam orientation optimization of the couch rotation.

Research Progress of Heavy Ion Radiotherapy for Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) has a high incidence and poses a serious threat to human health. However, the treatment outcomes of concurrent chemoradiotherapy for non-small-cell lung cancer are still unsatisfactory, especially for high grade lesions. As a new cancer treatment, heavy ion radiotherapy has shown promising efficacy and safety in the treatment of non-small-cell lung cancer. This article discusses the clinical progress of heavy ion radiotherapy in the treatment of non-small-cell lung cancer mainly from the different cancer stages, the different doses of heavy ion beams, and the patient’s individual factors, and explores the deficiency of heavy ion radiotherapy in the treatment of non-small-cell lung cancer and the directions of future research, in order to provide reference for the wider and better application of heavy ion radiotherapy in the future.

The effect of Laves phase on heavy-ion radiation response of Nb-containing FeCrAl alloy for accident-tolerant fuel cladding

As a promising candidate material for the accident tolerant fuel cladding in light water reactors, the Nb-containing FeCrAl alloy has shown outstanding out-of-pile service performance due to the Laves phase precipitation. In this work, the radiation response in FeCrAl alloys with gradient Nb content under heavy ion radiation has been investigated. The focus is on the effect of the Laves phase on irradiation-induced defects and hardening. We found that the phase boundary between the matrix and Laves phase can play a critical role in capturing radiation defects, as verified by in-situ heavy-ion radiation experiments and molecular dynamic simulations. Additionally, the evolution of Laves phase under radiation is analyzed. Radiation-induced amorphization and segregations observed at high radiation doses will deepen the fundamental understanding of the stability of Laves phases in the radiation environment.

Impacts of heavy metal, high temperature, and UV radiation exposures on Bellis perennis L. (common daisy): Comparison of phenolic constituents and antioxidant potential (enzymatic and non-enzymatic)

Bellis perennis L., common daisy, is a beneficial medicinal plant used in folk medicine to treat skin diseases, wounds, sore throats, common colds, inflammation, and rheumatism. The objective of this study was to determine the effect of 4 different abiotic stress applications [mercury chloride (HgCl2), copper sulfate (CuSO4), high temperature (45 °C) and ultraviolet radiation (UV)] on individual phenolic constituents, non-enzymatic antioxidant activities (free radical scavenging activity, total phenol-flavonoid content, and proline level), and enzymatic antioxidant activities [superoxide dismutase (SOD) and catalases (CAT)] in common daisy callus cultures. Quantification of the 21 phenolic substances was performed using LC-ESI-MS/MS analysis and all applied stress applications increased specific phenolic constituents comparing with control (no exposure to any stress). Heavy metal stresses (HgCl2 and CuSO4) and high temperature application enhanced the quantity of the selected phenolic substances more than UV-radiation stress. The most noticeable increased quantities were observed with high temperature stress in p-coumaric acid (51.74-fold), and with CuSO4 stress in luteolin (17.76-fold) and apigenin (15.62-fold). Chlorogenic acid was the most prevalent phenolic compound in all tested callus extract including control. Although the first highest total phenol content was obtained with HgCl2 exposure and then followed by high temperature stress, the first highest total flavonoid content was obtained with high temperature stress and then UV radiation. The antioxidant capacity was significantly enhanced (2.11 fold increase) with CuSO4 stress application. Stress-related enzymatic antioxidant activity (SOD and CAT) was elevated the most with HgCl2 stress. Similarly, the highest proline content was obtained with HgCl2 treatment. These findings showed the ability of the phenolic compounds to protect common daisy against harmful heavy metals, high temperature and UV-radiation stresses. The adaptation of the callus under abiotic stress conditions developed here may be useful for the production of optimized phenolic compounds of common daisy and the exploitation of other medicinal species of interest.

Structure and radiation response of anion excess bixbyite Gd2Ce2O7

The crystal structure analysis of ${\mathrm{Gd}}_{2}{\mathrm{Ce}}_{2}{\mathrm{O}}_{7}$ reveals that it crystallizes in a bixbyite-type symmetry ($I{2}_{1}3$). Analysis of the structure suggests a randomly occupied cation sublattice with infinite correlation length associated with long-range ordered anion sublattice with half of the vacant sites of an ideal bixbyite filled, hence the name anion-excess bixbyite. Ion irradiation experiments and quantitative x-ray diffraction analysis were used to study the separate response of the anion sublattice to swift heavy ion radiation. Analysis of anion and cation correlation lengths as a function of fluence shows that the topological disorder on the anion sublattice grows faster than that on the cation sublattice. The microstructural response at increasing radiation fluences leads to a decrease of the strain after an initial increase, while the variance of the strain increases following the increase of the microdomain wall density. This particular behavior seems responsible for the exceptional radiation resistance of this system that does not display any significant amorphization, even at the highest fluence.

Evaluation of the Saline-Alkaline Tolerance of Rice (Oryza sativa L.) Mutants Induced by Heavy-Ion Beam Mutagenesis.

Simple SummarySoil salinization is one of the important obstacles restricting agricultural development. Cultivating new varieties of saline–alkaline-tolerant rice can increase the yield of rice. It is possible to minimize breeding costs and shorten the breeding period through heavy ion beam irradiation mutation breeding. Our research evaluated and screened saline–alkaline-tolerant rice mutants induced by heavy ion beams. The results show that heavy ion beam radiation is an effective method for breeding new saline–alkaline-tolerant rice cultivars, and the selected mutant lines have excellent production performance under saline–alkaline stress. Our research results provide new theoretical and practical insights that can be used to help develop new saline–alkaline-tolerant rice cultivars.Soil salinity is a widespread and important abiotic factor impeding rice production by adversely affecting seed germination, seedling growth, and plant productivity. In this study, the rice cultivar TH899 was treated with 200 Gy of heavy-ion beam irradiation, and 89 mutant lines with stable phenotypes were selected using the pedigree method based on continuous assessment over six years. The seed germination performance of these mutants was tested under different saline–alkaline concentrations. Five highly tolerant lines were further evaluated in a series of experiments at the seedling stage and in the field. During the seedling stage, the reduction of seedling length, root length, fresh weight, and dry weight were dramatically lower in these five mutants than those in TH899 under saline–alkali stress. The K+/Na+ ratio was higher in these five mutants than in TH899. In the field experiment, the grain yield of mutant lines was higher than that of TH899. In addition, the grain yield of mutant line M89 was higher than that of the local cultivar in actual production. These mutant lines are expected to increase grain yield in soda saline–alkaline regions in northeast China.

Experimental investigation on heavy duty engine radiator using cerium oxide nano fluid

The goal of this work is to improve the heat transfer capacity of vehicle radiators by adding cerium oxide-based nanofluid, as well as to compare the performance analysis of radiators employing nanofluid with base fluid. By increasing heat transmission, this enhances heat transfer performance and engine efficiency of the radiator. Nanofluids are made by combining 3:2 water and ethylene glycol with 1% cerium oxide nanoparticles. This analysis has been performed in three distinct nanoparticle concentrations: 1%, 1.5%, and 2% by volume with different flow rate of 0.04, 0.05, 0.06, 0.07 and 0.08 kg/s. These modifications potentially increased the heat transfer rate by around 20% above the fluid (water). As a result, this demonstrates the usage of nanofluid in habitation of base fluid in boosting heat transfer rate by 6.2%, which aids in overall radiator performance enhancement. The experimental results showed a maximum enhancement of the “Nu” Nusselt numberby 13.39 percent with an inlet temperature of 60 °C, 2% Ceo2 nanomaterials, and a mass flow rate of 0.09 kg/s. The maximum increase in heat transfer rate is 6.2% with an inlet temperature of 60 °C, 2% Ceo2 nanoparticles, and a mass flow rate of 0.09 kg/s.

Reactive Oxygen Species (ROS): Key Components in Cancer Therapies.

Reactive Oxygen Species (ROS) refers to the highly reactive substances which contain oxygen radicals. Hypochlorous acid, peroxides, superoxide, singlet oxygen, alpha-oxygen, and hydroxyl radicals are the major examples of ROS. Generally, the reduction of oxygen (O2) in molecular form produces superoxide (•O2 -) anion. ROS are produced during a variety of biochemical reactions within the cell organelles, such as endoplasmic reticulum, mitochondria, and peroxisome. Naturally, ROS are also formed as a byproduct of the normal metabolism of oxygen. The production of ROS can be induced by various factors such as heavy metals, tobacco, smoke, drugs, xenobiotics, pollutants, and radiation. From various experimental studies, it is reported that ROS acts as either a tumor-suppressing or a tumor-promoting agent. The elevated level of ROS can arrest the growth of tumors through the persistent increase in cell cycle inhibition. The increased level of ROS can induce apoptosis by both intrinsic and extrinsic pathways. ROS is considered to be a tumor-suppressing agent as the production of ROS is due to the use of most of the chemotherapeutic agents in order to activate cell death. The cytotoxic effect of ROS provides impetus towards apoptosis, but in higher levels, ROS can cause initiation of malignancy that leads to uncontrolled cell death in cancer cells. In contrast, some species of ROS can influence various activities at the cellular level, including cell proliferation. This review highlights the genesis of ROS within cells by various routes and their role in cancer therapies.

Total body proton and heavy-ion irradiation causes cellular senescence and promotes pro-osteoclastogenic activity in mouse bone marrow

Low-LET photon radiation-induced persistent alterations in bone marrow (BM) cells are well documented in total-body irradiated (TBI) rodents and also among radiotherapy patients. However, the late effects of protons and high-LET heavy-ion radiation on BM cells and its implications in osteoclastogenesis are not fully understood. Therefore, C57BL6/J female mice (8 weeks; n = 10/group) were irradiated to sham, and 1 Gy of the proton (0.22 keV/μm), or high-LET 56Fe-ions (148 keV/μm) and at 60 d post-exposure, mice were sacrificed and femur sections were obtained for histological, cellular and molecular analysis. Cell proliferation (PCNA), cell death (active caspase-3), senescence (p16), osteoclast (RANK), osteoblast (OPG), osteoblast progenitor (c-Kit), and osteoclastogenesis-associated secretory factors (like RANKL) were assessed using immunostaining. While no change in cell proliferation and apoptosis between control and irradiated groups was noted, the number of BM megakaryocytes was significantly reduced in irradiated mice at 60 d post-exposure. A remarkable increase in p16 positive cells indicated a persistent increase in cell senescence, whereas increased RANKL/OPG ratio, reductions in the number of osteoblast progenitor cells, and osteocalcin provided clear evidence that exposure to both proton and 56Fe-ions promotes pro-osteoclastogenic activity in BM. Among irradiated groups, 56Fe-induced alterations in the BM cellularity and osteoclastogenesis were significantly greater than the protons that demonstrated a radiation quality-dependent effect. This study has implications in understanding the role of IR-induced late changes in the BM cells and its involvement in bone degeneration among deep-space astronauts, and also in patients undergoing proton or heavy-ion radiotherapy.

Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity.

The deep space environment contains many risks to astronauts during space missions, such as galactic cosmic rays (GCRs) comprised of naturally occurring heavy ions. Heavy ion radiation is increasingly being used in cancer therapy, including novel regimens involving carbon therapy. Previous investigations involving simulated space radiation have indicated a host of detrimental cognitive and behavioral effects. Therefore, there is an increasing need to counteract these deleterious effects of heavy ion radiation. Here, we assessed the ability of amifostine to mitigate cognitive injury induced by simulated GCRs in C57Bl/6J male and female mice. Six-month-old mice received an intraperitoneal injection of saline, 107 mg/kg, or 214 mg/kg of amifostine 1 h prior to exposure to a simplified five-ion radiation (protons, 28Si, 4He, 16O, and 56Fe) at 500 mGy or sham radiation. Mice were behaviorally tested 2–3 months later. Male mice that received saline and radiation exposure failed to show novel object recognition, which was reversed by both doses of amifostine. Conversely, female mice that received saline and radiation exposure displayed intact object recognition, but those that received amifostine prior to radiation did not. Amifostine and radiation also had distinct effects on males and females in the open field, with amifostine affecting distance moved over time in both sexes, and radiation affecting time spent in the center in females only. Whole-brain analysis of cFos immunoreactivity in male mice indicated that amifostine and radiation altered regional connectivity in areas involved in novel object recognition. These data support that amifostine has potential as a countermeasure against cognitive injury following proton and heavy ion irradiation in males.