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At least 1,765 records · Page 98
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity

Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodium selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p < 0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity. -- Highlights: ►Cisplatin resulted in diarrhea in mice by 88%. ►i.p. selenosulfate at 9.5 μmol/kg daily for 11 days reduced diarrhea to 6%. ►i.p. selenosulfate at 19 μmol/kg daily for 55 days was not toxic. ►i.p. selenite at 19 μmol/kg daily for 55 days was lethal. ►Innocuous dose of selenosulfate greatly prevents cisplatin-induced diarrhea.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose

Hemoglobin adducts have been used as biomarkers of exposure to reactive chemicals. Glycidol, an animal carcinogen, has been reported to form N-(2,3-dihydroxy-propyl)valine adducts to hemoglobin (diHOPrVal). To support the use of these adducts as markers of glycidol exposure, we investigated the kinetics of diHOPrVal formation and its elimination in vitro and in vivo. Five groups of rats were orally administered a single dose of glycidol ranging from 0 to 75 mg/kg bw, and diHOPrVal levels were measured 24 h after administration. A dose-dependent increase in diHOPrVal levels was observed with high linearity (R{sup 2} = 0.943). Blood sampling at different time points (1, 10, 20, or 40 days) from four groups administered glycidol at 12 mg/kg bw suggested a linear decrease in diHOPrVal levels compatible with the normal turnover of rat erythrocytes (life span, 61 days), with the calculated first-order elimination rate constant (k{sub el}) indicating that the diHOPrVal adduct was chemically stable. Then, we measured the second-order rate constant (k{sub val}) for the reaction of glycidol with N-terminal valine in rat and human hemoglobin in in vitro experiments with whole blood. The k{sub val} was 6.7 ± 1.1 and 5.6 ± 1.3 (pmol/g globin per μMh) in rat and human blood, respectively, indicating no species differences. In vivo doses estimated from k{sub val} and diHOPrVal levels were in agreement with the area under the (concentration–time) curve values determined in our earlier toxicokinetic study in rats. Our results indicate that diHOPrVal is a useful biomarker for quantification of glycidol exposure and for risk assessment. - Highlight: • Glycidol-hemoglobin adduct (diHOPrVal) was characterized for exposure evaluation. • We studied the kinetics of diHOPrVal formation and elimination in vitro and in vivo. • Dose dependent formation and chemical stability were confirmed in the rat study. • In vivo dose (AUC) of glycidol could be estimated from diHOPrVal levels. • diHOPrVal is considered a useful exposure and in vivo dose marker of G.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Moon, Mars and Minds: Evaluating Parkinson’s disease mortality among U.S. radiation workers and veterans in the million person study of low-dose effects

Background: Radiation is one of the most important stressors related to missions in space beyond Earth’s orbit. Epidemiologic studies of exposed workers have reported elevated rates of Parkinson’s disease. The importance of cognitive dysfunction related to low-dose rate radiation in humans is not defined. A meta-analysis was conducted of six cohorts in the Million Person Study (MPS) of low-dose health effects to learn whether there is consistent evidence that Parkinson’s disease is associated with radiation dose to brain. Materials and methods: The MPS evaluates all causes of death among U.S. radiation workers and veterans, including Parkinson’s disease. Systematic and consistent methods are applied to study all categories of workers including medical radiation workers, industrial radiographers, nuclear power plant workers, atomic veterans, and Manhattan Projects workers at the Los Alamos National Laboratory and at Rocky Flats. Consistent methods for all cohorts are used to estimate organ-specific doses and to obtain vital status and cause of death. Results: The meta-analysis include 6 cohorts within the MPS, consisting of 517,608 workers and 17,219,001 person-years of observation. The mean dose to brain ranged from 6.9 to 47.6 mGy and the maximum dose from 0.76 to 2.7 Gy. Five of the 6 cohorts revealed positive associations with Parkinson’s disease. The overall summary estimate from the meta-analysis was statistically significant based on 1573 deaths due to Parkinson’s disease. The summary excess relative risk at 100 mGy was 0.17 (95% CI: 0.05; 0.29). Conclusions: Parkinson’s disease was positively associated with radiation in the MPS cohorts indicating the need for careful evaluation as to causality in other studies, delineation of possible mechanisms, and assessing possible implications for space travel as well as radiation protection guidance for terrestrial workers.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Repetitive Dosing of Fumed Silica Leads to Profibrogenic Effects through Unique Structure–Activity Relationships and Biopersistence in the Lung

Contrary to the notion that the use of fumed silica in consumer products can “generally (be) regarded as safe” (GRAS), the high surface reactivity of pyrogenic silica differs from other forms of synthetic amorphous silica (SAS), including the capacity to induce membrane damage and acute proinflammatory changes in the murine lung. Additionally, the chain-like structure and reactive surface silanols also allow fumed silica to activate the NLRP3 inflammasome, leading to IL-1β production. This pathway is known to be associated with subchronic inflammation and profibrogenic effects in the lung by α-quartz and carbon nanotubes. Different from the latter materials, bolus dose instillation of 21 mg/kg fumed silica did not induce sustained IL-1β production or subchronic pulmonary effects. In contrast, the NLRP3 inflammasome pathway was continuously activated by repetitive-dose administration of 3 × 7 mg/kg fumed silica, 1 week apart. We also found that while single-dose exposure failed to induce profibrotic effects in the lung, repetitive dosing can trigger increased collagen production, even at 3 × 3 mg/kg. The change between bolus and repetitive dosing was due to a change in lung clearance, with recurrent dosing leading to fumed silica biopersistence, sustained macrophage recruitment, and activation of the NLRP3 pathway. These subchronic proinflammatory effects disappeared when less surface-reactive titanium-doped fumed silica was used for recurrent administration. Finally, these data indicate that while fumed silica may be regarded as safe for some applications, we should reconsider the GRAS label during repetitive or chronic inhalation exposure conditions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

A new platform for ultra-high dose rate radiobiological research using the BELLA PW laser proton beamline

Abstract Radiotherapy is the current standard of care for more than 50% of all cancer patients. Improvements in radiotherapy (RT) technology have increased tumor targeting and normal tissue sparing. Radiations at ultra-high dose rates required for FLASH-RT effects have sparked interest in potentially providing additional differential therapeutic benefits. We present a new experimental platform that is the first one to deliver petawatt laser-driven proton pulses of 2 MeV energy at 0.2 Hz repetition rate by means of a compact, tunable active plasma lens beamline to biological samples. Cell monolayers grown over a 10 mm diameter field were exposed to clinically relevant proton doses ranging from 7 to 35 Gy at ultra-high instantaneous dose rates of 10 7 Gy/s. Dose-dependent cell survival measurements of human normal and tumor cells exposed to LD protons showed significantly higher cell survival of normal-cells compared to tumor-cells for total doses of 7 Gy and higher, which was not observed to the same extent for X-ray reference irradiations at clinical dose rates. These findings provide preliminary evidence that compact LD proton sources enable a new and promising platform for investigating the physical, chemical and biological mechanisms underlying the FLASH effect.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2020

Subtoxic dose of lithium cobalt oxide nanosheets impacts critical molecular pathways in trout gill epithelial cells

Increasing use of nanoscale lithium cobalt oxide (LCO) particles in nanotechnologies, including catalysis and energy storage, raises concerns over their release into the environment and subsequent biological impact. Here we study the impact of LCO nanosheets on trout gill epithelial cells – model cells for environmental exposures – by global transcriptomics using RNA-Seq. We identify molecular processes impacted by subtoxic and toxic nanoparticle (NP) doses as well as dissolved Li+ and Co2+ ions. We found that the ions, at concentrations released from the toxic NP dose, did not impact cell viability and downregulated the expression of few genes following 24 h exposure, which recovered to normal levels at 48 h. In contrast, the toxic NP dose upregulated the expression of over 1000 genes at each time point, indicating the intact NPs are responsible for perturbing gene expression and toxicity. Importantly, the subtoxic NP dose, despite having no impact on cell viability, upregulated the expression of over 500 genes at 24 h, and 150 genes at 48 h. Clustering analysis showed distinct gene expression profiles induced by the toxic and subtoxic NP doses, and functional enrichment identified pathways with distinct patterns of regulations. The impacted pathways fell into four main functional categories: metabolic and energy related processes, oxygen and hypoxia related processes, membrane binding and internalization processes, and developmental processes. Together, our observations indicate that LCO NP toxicity originates from the intact NP, not the dissolved ions, and even subtoxic NP dose impacts multiple pathways critical to the normal function of the cell.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

Dose-rate dependence of damage buildup in 3 C -SiC

The influence of the defect generation rate on radiation damage processes in SiC remains poorly understood. Here, we use a combination of ion channeling and transmission electron microscopy to systematically study the dose-rate dependence of damage buildup in 3C-SiC bombarded in the temperature range of 25–200 °C with 500 keV Ar ions. The results reveal a pronounced dose-rate effect, whose magnitude increases close-to-linearly with temperature. When ion dose and temperature are held constant, the dose-rate dependence of the damage level is nonlinear, with saturation at high dose rates. Electron microscopy reveals that the average size of stable defect clusters increases with increasing dose rate. These findings have important implications for understanding and predicting radiation damage in SiC.

Bayu Aji, L. B. (ORCID:0000000315573023)↗
DOE OSTI2025

Evaluation of PBR Spent Fuel Criticality and Dose Rate Compliance for Storage and Transportation

Spent tri-structural isotropic (TRISO)–based fuels have a strong track record in storage and transportation without documented incidents. This work seeks to reduce uncertainty to aid in more informed spent fuel management of TRISO-based fuels by modeling both fresh and spent pebble bed reactor (PBR) fuel and comparing the results to the regulatory standards from 10 CFR 71. SCALE was used for all modeling due to it having fast and accurate methods for handling PBR fuel modeling, as well as having an efficient method for shielding calculations in monaco with automated variance reduction using importance calculations (MAVRIC), which utilizes the consistent adjoint-driven importance sampling (CADIS) and the forward-weighted consistent adjoint-driven importance sampling (FW-CADIS) methods. KENO-VI was used for all criticality calculations, TSUNAMI was used for uncertainty quantification on k-effective, TRITON and the Oak Ridge isotope generation code (ORIGEN) were both used for depletion of the fuel, and MAVRIC was used for shielding calculations. For criticality assessments, this study focused on the requirement that the value of the neutron multiplication factor, k-effective (k-eff), would not exceed a peak value of 0.95, including uncertainty, with 95% confidence. Criticality was initially examined by modeling fresh fuel from three different designs—HTR-10 fuel, PBMR-400 fuel, and demonstration fuel representative of a TRISO-fueled modern high-temperature gas reactor (HTGR) design, henceforth referred to as Demo HTGR—and placing them into various sized containers with conditions described in 10 CFR 71 to quantify the peak k-eff state. When the peak value of 0.95 k-eff was exceeded, mitigation methods were examined in those scenarios. Burnup credit, pebble displacement in areas of strong neutron multiplication, and random pebble replacement using pebbles of various compositions and replacement fractions were examined. In summary, the criticality of PBR fuels can be well accounted for by restricting container size, taking credit for burnup, or by displacing/replacing pebbles. Uncertainty of the k-eff due to nuclear data uncertainties was recorded at ~0.6644%Δk/k, or roughly 664% mil (pcm). The nuclear data–induced uncertainty was relatively small and should not require significant modification in the design to be accounted for. Revisions to the evaluated nuclear data file values have been shown to have a larger impact than nuclear data–induced uncertainty. For dose rate aspects, U.S. Nuclear Regulatory Commission regulations require a maximum dose rate of 10 millirem per hour (mrem/h) at 2 meters. In examining the dose rate behavior of spent PBR fuel, the representative Demo HTGR fuel was modeled exclusively due to it possessing the highest target burnup of the examined fuels. Equilibrium cycle modeling methods were used to produce a higher-fidelity discharge isotopic composition than simple assumptions, such as reflected pebbles. The discharge composition was used as a source term in the fixed-source transport shielding calculations, and dose rates were calculated at 2 m for the shortest possible cooling time. The low concentration of fuel material led to dose rates that were in line with regulatory limits, despite the high burnup when compared to traditional light water reactor fuels. In conclusion, the methods employed in this study would require more work to further verify and validate and are limited to the criticality and dose rate analyses performed.

11 - NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2018

Dosimetry and uncertainty approaches for the million person study of low-dose radiation health effects: overview of the recommendations in NCRP Report No. 178

Purpose: Scientific Committee 6–9 was established by the National Council on Radiation Protection and Measurements (NCRP), charged to provide guidance in the derivation of organ doses and their uncertainty, and produced a report, NCRP Report No. 178, Deriving Organ Doses and their Uncertainty for Epidemiologic Studies with a focus on the Million Person Study of Low-Dose Radiation Health Effects (MPS). This review summarizes the conclusions and recommendations of NCRP Report No. 178, with a concentration on and overview of the dosimetry and uncertainty approaches for the cohorts in the MPS, along with guidelines regarding the essential approaches used to estimate organ doses and their uncertainties (from external and internal sources) within the framework of an epidemiologic study. Conclusions: The success of the MPS is tied to the validity of the dose reconstruction approaches to provide realistic estimates of organ-specific radiation absorbed doses that are as accurate and precise as possible and to properly evaluate their accompanying uncertainties. Further, the dosimetry aspects for the MPS are challenging in that they address diverse exposure scenarios for diverse occupational groups being studied over a period of up to 70 y. Specific dosimetric reconstruction issues differ among the varied exposed populations that are considered: atomic veterans, U.S. Department of Energy workers exposed to both penetrating radiation and intakes of radionuclides, nuclear power plant workers, medical radiation workers, and industrial radiographers. While a major source of radiation exposure to the study population comes from external gamma- or x-ray sources, for some of the study groups, there is also a meaningful component of radionuclide intakes that requires internal radiation dosimetry assessments.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

Dose rate effects in the radiation damage of the plastic scintillators of the CMS hadron endcap calorimeter

We present measurements of the reduction of light output by plastic scintillators irradiated in the CMS detector during the 8 TeV run of the Large Hadron Collider and show that they indicate a strong dose rate effect. The damage for a given dose is larger for lower dose rate exposures. The results agree with previous measurements of dose rate effects, but are stronger due to the very low dose rates probed. Here, we show that the scaling with dose rate is consistent with that expected from diffusion effects.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2020

Coefficients for Estimating Prenatal Dose in Pregnant Workers from Acute Intakes

Inhalation and ingestion dose coefficients for the embryo and fetus from intakes of radionuclides by the mother are provided in the International Commission on Radiological Protection (ICRP) Publication 88 for intake of each of 74 radionuclides. To address the many other possible radionuclides to which workers may be exposed, effective dose coefficients were developed for the embryo/fetus for all additional radionuclides addressed in ICRP Publication 107 with half-life of 10 min or more. The general approach was to use the estimated dose to the mother’s uterus during pregnancy as a scalable proxy for the dose to the embryo/fetus. The set of scaling factors used in the study was derived from analyses of the relationships of the dose to the mother’s uterus and the effective dose to the embryo/fetus for the ~400 cases (considering two intake modes and multiple forms of many of the radionuclides) addressed in Publication 88.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2023

The Effects of Gamma Ray Integrated Dose on a Commercial 65-nm SRAM Device

Here this work shows that the static random access memory (SRAM) error rate for a commercial 65-nm device in a dose rate environment can be highly dependent upon the integrated dose (dose rate × pulse duration). While the typical metric for such testing is dose rate upset (DRU) level in rad(Si)/s, a series of dose rate experiments at Little Mountain Test Facility (LMTF) shows dependence on the integrated dose. The error rate is also found to be dependent on the core voltage, and the preradiation value of the bits. We believe that these effects are explained by a well charge depletion caused by gamma ray photocurrent.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2014

SU-E-T-340: Use of Intensity Modulated Proton Therapy (IMPT) for Reducing the Dose to Cochlea in Craniospinal Irradiation (CSI) of Pediatric Patients

Purpose: To evaluate use of intensity modulated proton therapy (IMPT) and number of beams for sparing cochlea in treatment of whole brain for pediatric medulloblastoma patients. Methods: In our institution, craniospinal irradiation patients are treated in supine position on our proton gantries using pencil beam scanning with each beam uniformly covering the target volume (SFUD). Each treatment plan consists of two opposed lateral whole brain fields and one or two spinal fields. For sparing the cochlea for the whole brain treatment, we created three different plans using IMPT for five pediatric patients. The first plan consisted of two lateral fields, the second two lateral fields and a superior-inferior field, and the third two lateral fields and two superior oblique fields. Optimization was performed with heavy weights applied to the eye, lens and cochlea while maintaining a dose prescription of 36 Gy to the whole brain. Results: IMPT plans reduce the dose to the cochlea. Increasing the number of treatment fields was found to lower the average dose to the cochlea: 15.0, 14.5 and 12.5 Gy for the two-field, three-field, and four-field plans respectively. The D95 for the two-field plan was 98.2%, compared to 100.0% for both the three-field and four-field plan. Coverage in the mid-brain was noticeably better in the three- and four-field plans, with more dose conformality surrounding the cochlea. Conclusion: IMPT plans for CSI and the whole brain irradiations are capable of sparing cochlea and reduce the dose considerably without compromising treating brain tissues. The reduction in average dose increases with three and four field plans as compared to traditional two lateral beam plans.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-F-BRD-06: Robust Dose Calculation in Intensity Modulated Proton Therapy

Purpose: Commissioning data for intensity modulated proton therapy (IMPT) must be post-processed by fits to ad-hoc functions to derive the dose calculation kernel parameters in a treatment planning system (TPS). Whether from experimental measurement or Monte Carlo simulation, the limited and noisy nature of such data makes this task very challenging. We present a method to improve the modeling of the lateral dose distribution of clinical energy proton beams in water to commission an in-house IMPT dose calculation engine. Methods: A linear sum of three Gaussian distribution functions was fitted to the lateral dose data in logarithmic scale. Starting values of fitting solutions were determined from the Generalized Highland Approximation. We exhaustively optimized the combinations of data weights with upper bounds of the fitting solutions to minimize confidence intervals of the fitting solutions while maintaining the coefficient of determination (R{sup 2}). Results: Across all energies, average confidence bounds improved 72.88% [Max: 88.28%, Min: 55.05%] for small angle coulomb scattering, 114.25% [409.13%, 66.72%,] for nuclear scattering, and 68.66% [141.09%, 33.27%] for large angle coulomb scattering, while the coefficients of determination of the fits (R{sup 2}) remained comparable. On average R {sup 2} only changed 0.18% and were very close to 1 (approx. 0.999). Wilcoxon signed rank tests comparing unweighted/unbounded fits with weighted/bounded fits averaged 0.0146 (Max: 0.177, Min: 7.05×10−{sup 7}) for small angle Coulomb, 0.0903 (0.945, 7.05×10−{sup 7}) for nuclear, and 0.254 (0.871, 1.86×10−{sup 6}) for large angle Coulomb scattering. This allows rejection of the null hypothesis for small angle Coulomb scattering at the 0.015 level and nuclear interaction at the 0.1 level. Conclusion: Optimal weights assigned to IMPT lateral dose data minimized fitting to stochastic noise in the tail region. Optimizing the upper bounds of fitting parameters improved the robustness of fitting solutions. Both led to a more physically meaningful dose calculation kernel for the TPS. NIH/NCI K25CA168984, Eagles Cancer Research Career Development, The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, Mayo ASU Seed Grant, and The Kemper Marley Foundation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-361: Dose Enhancement Due to Nanoparticle Addition in Skin Radiotherapy: A Monte Carlo Study Using Kilovoltage Photon Beams

Purpose: This study investigated the dose enhancement due to addition of nanoparticles with different types and concentrations in skin radiotherapy using kilovoltage photon beams. Methods: An inhomogeneous water phantom (15×15×10 cm{sup 3}) having the skin target layer (0.5–5 mm), added with different concentrations (3–40 mg/ml) of nanoparticles (Au, Pt, I, Ag and Fe{sub 2}O{sub 3}), was irradiated by the 105 and 220 kVp photon beams produced by a Gulmay D3225 Orthovoltage unit. The circular cone of 5-cm diameter and source-to-surface distance of 20 cm were used. Doses in the skin target layer with and without adding the nanoparticles were calculated using Monte Carlo simulation (the EGSnrc code) through the macroscopic approach. Dose enhancement ratio (DER), defined as the ratio of dose at the target with nanoparticle addition to the dose without addition, was calculated for each type and concentration of nanoparticle in different target thickness. Results: For Au nanoparticle, DER dependence on target thickness for the 220 kVp photon beams was not significant. However, DER for Au nanoparticle was found decreasing with an increase of target thickness when the nanoparticle concentration was increased from 18 to 40 mg/ml using the 105 kVp photon beams. For nanoparticle concentration of 40 mg/ml, DER variation with target thickness was not significant for the 220 kVp photon beams, but DEF was found decreasing with the target thickness when lower energy of photon beam (105 kVp) was used. DEF was found increasing with an increase of nanoparticle concentration. The higher the DEF increasing rate, the higher the atomic number of the nanoparticle except I and Ag for the same target thickness. Conclusion: It is concluded that nanoparticle addition can result in dose enhancement in kilovoltage skin radiotherapy. Moreover, the DER is related to the photon beam energy, target thickness, atomic number and concentration of nanoparticles.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

False Indications of Dose-Response Nonlinearity in Large Epidemiologic Cancer Radiation Cohort Studies; A Simulation Exercise

This study explores the likely prevalence of false indications of dose-response nonlinearity in large epidemiologic cancer radiation cohort studies (A-bomb survivors, INWORKS, Techa River). Reasons: Increasing numbers of tests of nonlinearity are being made in studies. Hypothesized nonlinear dose-response models have been justified to policy makers by analyses that rely in part on isolated findings that could be statistical fluctuations. After removing dose nonlinearity (linearization) by adjusting person-years of observation at each dose category, indications of nonlinearity, necessarily false, were counted in 5,000 randomized replications of six datasets. The average frequency of any false positive for five indicators of nonlinearity tested against a linear null was roughly 25% in Monte Carlo simulations per study, consistent with binomial calculations, increasing to ~50% within 6 studies assessed. Comparable frequencies were found using Akaike's information criterion (AIC) for model selection or multi-model averaging. False above-zero threshold doses were found more than 50% of the time, averaging to 0.05 Gy, consistent with findings in the 6 studies. Such bias, uncorrected, could distort meta-analyses of multiple studies, because meta-analyses can incorporate high P value findings. AIC-based correction for the extra threshold parameter lowered these false occurrences to 8 to 19%. Given the simulation rates, the possibility of false positives might be noted when isolated findings of nonlinearity are discussed in a regulatory context. When reporting a threshold dose with a P value > 0.05, it would be informative to note the expected high false prevalence rate due to bias.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

A Novel Platform for Evaluating Dose Rate Effects on Oxidative Damage to Peptides: Toward a High-Throughput Method to Characterize the Mechanisms Underlying the FLASH Effect

High dose rate radiation has gained considerable interest recently as a possible avenue for increasing the therapeutic window in cancer radiation treatment. The sparing of healthy tissue at high dose rates relative to conventional dose rates, while maintaining tumor control, has been termed the FLASH effect. Although the effect has been validated in animal models using multiple radiation sources, it is not yet well understood. Here, in this work, we demonstrate a new experimental platform for quantifying oxidative damage to protein sidechains in solution as a function of radiation dose rate and oxygen availability using liquid chromatography mass spectrometry. Using this reductionist approach, we show that for both X-ray and electron sources, isolated peptides in solution are oxidatively modified to different extents as a function of both dose rate and oxygen availability. Our method provides an experimental platform for exploring the parameter space of the dose rate effect on oxidative changes to proteins in solution.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

Neurogenic Effects of Low-Dose Whole-Body HZE (Fe) Ion and Gamma Irradiation

Understanding the dose-toxicity profile of radiation is critical when evaluating potential health risks associated with natural and man-made sources in our environment. This study was done to evaluate the effects of low-dose whole-body high-energy charged (HZE) iron (Fe) ions and low-energy gamma exposure on proliferation and differentiation of adult-born neurons within the dentate gyrus of the hippocampus, cells deemed to play a critical role in memory regulation. To determine the dose-response characteristics of the brain to whole-body Fe-ion vs. gamma-radiation exposure, C57BL/6J mice were irradiated with 1 GeV/n Fe ions or a static 137 Cs source (0.662 MeV) at doses ranging from 0 to 300 cGy. The neurogenesis was analyzed at 48 h and one month postirradiation. These experiments revealed that whole-body exposure to either Fe ions or gamma radiation leads to: 1. An acute decrease in cell division within the dentate gyrus of the hippocampus, detected at doses as low as 30 and 100 cGy for Fe ions and gamma radiation, respectively; and 2. A reduction in newly differentiated neurons (DCX immunoreactivity) at one month postirradiation, with significant decreases detected at doses as low as 100 cGy for both Fe ions and gamma rays. The data presented here contribute to our understanding of brain responses to whole-body Fe ions and gamma rays and may help inform health-risk evaluations related to systemic exposure during a medical or radiologic/nuclear event or as a result of prolonged space travel.

61 RADIATION PROTECTION AND DOSIMETRY↗