A comparative study on the dose-effect of low-dose radiation based on microdosimetric analysis and single-cell sequencing technology.

The biological mechanisms triggered by low-dose exposure still need to be explored in depth. In this study, the potential mechanisms of low-dose radiation when irradiating the BEAS-2B cell lines with a Cs-137 gamma-ray source were investigated through simulations and experiments. Monolayer cell population models were constructed for simulating and analyzing distributions of nucleus-specific energy within cell populations combined with the Monte Carlo method and microdosimetric analysis. Furthermore, the 10 × Genomics single-cell sequencing technology was employed to capture the heterogeneity of individual cell responses to low-dose radiation in the same irradiated sample. The numerical uncertainties can be found both in the specific energy distribution in microdosimetry and in differential gene expressions in radiation cytogenetics. Subsequently, the distribution of nucleus-specific energy was compared with the distribution of differential gene expressions to guide the selection of differential genes bioinformatics analysis. Dose inhomogeneity is pronounced at low doses, where an increase in dose corresponds to a decrease in the dispersion of cellular-specific energy distribution. Multiple screening of differential genes by microdosimetric features and statistical analysis indicate a number of potential pathways induced by low-dose exposure. It also provides a novel perspective on the selection of sensitive biomarkers that respond to low-dose radiation.

γ-H2AX and phospho-ATM enzyme-linked immunosorbent assays as biodosimetry methods for radiation exposure assessment: a pilot study.

In the event of a radiological incident, a fast and accurate biological dosimetry (biodosimetry) method for evaluating people who have been potentially exposed to ionising radiation is crucial. Among the many biodosimetry methods available, the immunodetection of phosphorylated H2AX (γ-H2AX) stands as a promising method to be used in the triage of patients exposed to radiation. Currently, the most common way to measure γ-H2AX levels is through fluorescence microscopy. In this pilot study, we assessed the feasibility of using an enzyme-linked immunosorbent assay (ELISA) for quantifying γ-H2AX for biodosimetry purposes. Moreover, the usefulness of measuring phosphorylated ATM (pATM) levels through ELISA for biodosimetry was also evaluated. Blood samples were obtained from three male donors (38 y) and were irradiated with 60Co (0, 1, 2 and 6 Gy). Peripheral blood mononuclear cells (PBMCs) were isolated and lysed before measuring γ-H2AX, total H2AX protein and pATM using ELISA kits. The dicentric chromosome assay (DCA) using whole blood was also performed for comparison. Data from all donors at each dose were pooled before statistical analysis. The ratio of γ-H2AX/total H2AX and pATM levels increased in a radiation-dose-dependent manner. The average γ-H2AX/total H2AX ratios were 0.816 ± 0.219, 0.830 ± 0.685, 1.276 ± 1.151 and 1.606 ± 1.098, whereas the average levels of pATM were 59.359 ± 3.740, 63.366 ± 0.840, 66.273 ± 2.603 and 69.936 ± 4.439, in PBMCs exposed to 0, 1, 2 and 6 Gy, respectively. The linear-quadratic dose-response calibration curve for DCA was Y = 0.0017 (±0.0010) + 0.0251 (±0.0142) × D + 0.0342 (±0.0039) × D2  $\boldsymbol{Y}=\mathbf{0.0017}\left(\pm \mathbf{0.0010}\right)+\mathbf{0.0208}\left(\pm \mathbf{0.0218}\right)\times \boldsymbol{D}+\mathbf{0.0350}\left(\pm \mathbf{0.0050}\right)\times{\boldsymbol{D}}^{\mathbf{2}}$. Overall, despite a large variability in the ratio of γ-H2AX/total H2AX among donors, the present study revealed the suitability of using the ratio of γ-H2AX/total H2AX and pATM for biodosimetry. Still, more research with a larger group of subjects is necessary to construct a reliable calibration curve for the ratio of γ-H2AX/total H2AX and pATM levels for biodosimetry.

Muller mistakes: The linear no-threshold (LNT) dose response and US EPA's cancer risk assessment policies and practices.

This paper identifies the occurrence of six major conceptual scientific errors of Hermann Muller and describes how these errors led to the creation of the linear no-threshold (LNT) dose response historically used worldwide for cancer risk assessments for chemical carcinogens and ionizing radiation. The paper demonstrates the significant role that Muller played in the environmental movement, affecting risk assessment policies and practices that are in force even now a half century following his death. This paper lends support to contemporary research that shows significant limitations of the LNT model for cancer risk assessment.

Dependence of Induced Biological Damage on the Energy Distribution and Intensity of Clinical Intra-Operative Radiotherapy Electron Beams.

The survival fraction of epithelial HaCaT cells was analysed to assess the biological damage caused by intraoperative radiotherapy electron beams with varying energy spectra and intensities. These conditions were achieved by irradiating the cells at different depths in water using nominal 6 MeV electron beams while consistently delivering a dose of 5 Gy to the cell layer. Furthermore, a Monte Carlo simulation of the entire irradiation procedure was performed to evaluate the molecular damage in terms of molecular dissociations induced by the radiation. A significant agreement was found between the molecular damage predicted by the simulation and the damage derived from the analysis of the survival fraction. In both cases, a linear relationship was evident, indicating a clear tendency for increased damage as the averaged incident electron energy and intensity decreased for a constant absorbed dose, lowering the dose rate. This trend suggests that the radiation may have a more pronounced impact on surrounding healthy tissues than initially anticipated. However, it is crucial to conduct additional experiments with different target geometries to confirm this tendency and quantify the extent of this effect.

Assessment of uncertainties in threshold doses for tissue reactions following acute external radiation exposure.

The study aimed to estimate threshold doses and their uncertainties for some human health effects after short-term high dose-rate radiation exposure by quantile technique and the effective dose threshold technique based on distribution functions. The relative uncertainty (U) of the threshold dose was estimated using the error propagation technique. The quantile technique provided statistically significant estimates of threshold doses for acute radiation syndrome onset (0.44 ± 0.12 Gy, U = 143%) and lethality (1.84 ± 0.44 Gy, U = 117%) but relative uncertainties were high. The effective threshold dose technique provided statistically significant and more precise threshold dose estimates for acute radiation syndrome onset (0.73 ± 0.02 Gy, U = 18%) and lethality (6.83 ± 0.08 Gy, U = 36%), as well as agranulocytosis (3.51 ± 0.03 Gy, U = 16%) and vomiting onset in the prodromal period (1.54 ± 0.02 Gy, U = 16%). Threshold doses estimated for the change in the peripheral blood neutrophil and leukocyte counts during the first days after short-term high dose-rate radiation exposure were not statistically significant.

Thresholds for radiation induced mutation? The Muller-Evans debate: A turning point for cancer risk assessment.

In 1949 Robley Evans [1] published a paper in Science supporting a threshold dose response for ionizing radiation-induced mutation, contradicting comments of Hermann Muller during his 1946 Nobel Prize Lecture [2] and subsequent presentations. Evans sent a final draft [3] prior to publication to over 50 leading geneticists/radiologists, including Muller, with this correspondence being generally extremely supportive, including letters from the radiation geneticists Curt Stern, James Neel and Donald Charles. Of interest is that Muller engaged in a dispute with Evans, with Evans dismissing Muller's comments as containing "a few points of scientific interest, and many matters pertaining to personalities and prejudices." A foundation of the Evans threshold position was the study by Ernst Caspari, which was done under the direction of Curt Stern, at the University of Rochester/Manhattan Project, and for which Muller was a paid consultant, thereby having insider knowledge of the research team, results and internal debates. Muller published a series of articles after the Evans Science publication that marginalized the Caspari findings, claiming that his control group was aberrantly high, which caused his threshold conclusion to be incorrect. Internal correspondence in 1947 between Muller and Stern reveals that Muller supported the use of the Caspari control group based on consistency with his own laboratory data. This correspondence shows that Muller reversed his position three years later, soon after the Evans publication. In that same 1947 correspondence with Stern, Muller also claimed that the mutational findings of Delta Uphoff, who was replicating the Caspari study, could not be supported because of aberrantly low control group values only to reverse himself to support the LNT model. The present paper links Muller's threshold rejection/LNT supporting actions to the timing of the debate with Evans concerning Evans' use of the Caspari data to support the threshold model. It is of historical significance that the duplicitous actions of Muller were rewarded, with his newly expressed reversed views becoming generally accepted (while his previously documented contrary views were hidden/remained private). At the same time, the marginalizing of the Caspari findings greatly impacted recommendations to support LNT by major advisory committees.

Evolution frames the dose response for all endpoints including application to cancer risk assessment: Time for a mid-course correction.

An underappreciated perspective is that the quantitative features of the dose-response in the low dose zone are a genetically based biological characteristic with a highly conserved evolutionary basis. Failure to recognize and take this into account has been a major failing of toxicology and radiation biology, affecting regulatory agencies worldwide. The present perspective clarifies the historical foundations of this misstep and calls for a mid- course correction that replaces the public health based Precautionary Principle for risk assessment with one based on the principles of evolutionary biology.

Dose response and risk assessment: Evolutionary foundations.

The present paper indicates that the origin of the LNT concept for ionizing radiation was based on insufficient understanding of evolution, which precluded the possibility of repair of gene mutation. The denial of such repair processes had important implications, leading to a belief in a linear dose response and thus in Hermann J Muller's proclamation of a Proportionality Rule for ionizing radiation. The paper documents how the lack of repair concept dominated the radiation geneticist community to the 1960s leading to the establishment of the linear no threshold dose response (LNT) model for radiation and chemical reproductive and cancer risk assessment. Research from the late 1950s onward would establish the occurrence, generality, and efficacy of genetic and cellular repair processes. While the assumption of a lack of gene mutation repair was wrong, Muller was correct that dose-response concepts need to be founded on mechanistic understandings of evolution. Such mechanisms require the integration of constitutive and inducible adaptive and repair mechanisms that operate in the low-dose zone. This perspective reflects the comment of Dobzhansky (1973) that "nothing makes sense in biology except in light of evolution." While this is a powerful scientific dictum, it assumes a correct understanding of evolution, something that the origins of the LNT dose response lacked. Such modern mechanistic repair developments reveal that the historical foundations of LNT were flawed from the start. Nonetheless, they have been carried forward to the present time, principally by environmental health regulatory agencies that decoupled risk assessment policy from a sound evolutionary foundation.

Ethical challenges of the linear non-threshold (LNT) cancer risk assessment revolution: History, insights, and lessons to be learned.

This paper provides historical review and evaluation of the development, adoption, and advocacy of the linear non-threshold (LNT) dose response model for cancer risk assessment as applied in practices and policies worldwide. It extends previous historical assessments and provides novel insights regarding: 1) how LNT bias became institutionalized in US governmental agencies, 2) how improper editorial practices at the journal Science promoted the adoption of LNT, 3) how a Nobel Prize winning scientist unjustifiably espoused and influenced support for replacing the threshold dose response model with the LNT model, 4) how the cover-up of striking and substantial experimental cancer data by US government scientists reduced support for the threshold dose response model at a critical period of cancer risk assessment policy adoption, and 5) how these events have negatively influenced cancer risk assessment practices and environmental and public health decisions for decades. These findings are presented to illustrate how profound and recognized mistakes, biases and unethical activities, inclusive of frank scientific misconduct, converged, and should motivate regulatory agencies worldwide to critically evaluate any existing policies that apply the LNT model as well as to serve as object lessons for current and future ethical conduct of research, and the provision of ethico-legal education in and across scientific curricula and institutions.

Key historical study findings questioned in debate over threshold versus linear non-threshold for cancer risk assessment.

This paper demonstrates that the dissertation research of Ray-Chaudhuri (1939, 1944) that was used by Hermann Muller to support his radiation induced gene mutation hypothesis and linear non-threshold (LNT) dose response model during his Nobel Prize Lecture is "uninterpretable" with respect to these issues. The research failed to include essential research design information, resulting in reporting flaws that have never been previously identified. These observations are historically important because this dissertation was used to blunt powerful criticism of Muller's gene mutation research and strongly promoted his advocacy of the LNT model in radiation risk assessment.

In Vivo Quantitative Assessment of a Radiation Dose Based on Ratiometric Photoacoustic Imaging of Tumor Apoptosis.

Accurately assessing the radiation level of tumors and surrounding tissues is of great significance for the optimization of clinical therapeutic interventions as well as minimizing the radiation-induced side effects. Therefore, the development of noninvasive and sensitive biological dosimeters is vital to achieve quantitative detection of a radiation dose in a living system. Herein, as a proof of concept, we report a tumor-targeted and caspase-3-activatable NIR fluorogenic probe AcDEVD-Cy-RGD consisting of a hemicyanine fluorophore as a signal reporter, a caspase-3 specific Asp-Glu-Val-Asp (DEVD) peptide, and a cyclic Arg-Gly-Asp peptide (cRGD) for tumor targeting. Upon cleavage with activated caspase-3, this probe not only displays the lighted-up NIR fluorescence, but also ratiometric photoacoustic (PA710/PA680) signals concurrently in a caspase-3 concentration-dependent manner, allowing for sensitive and quantitative detection of caspase-3 activity through both fluorescence and PA imaging, which provides the possibility for real-time monitoring of tumor cell apoptosis in a living system. More notably, we utilized this probe to successfully realize the direct visualization of tumor response to chemo- or radiotherapy and, for the first time, achieve the accurate estimation of radiation doses imparted to the tumors. We thus believe that our current strategy would offer an attractive and valuable means for the precise assessment of locally delivered radiation doses in various clinical settings.

A hypothesis to derive the shape of the dose-response curve for teratogenic radiation effects.

Reports of adverse pregnancy outcomes after in utero exposure to very low levels of ionizing radiation are inconsistent with a threshold dose of 100 mSv for teratogenic effects in humans. In the present study, it is hypothesized that the shape of the dose-response relationship for teratogenic effects is a cumulative lognormal distribution without threshold. This hypothesis relies on the assumption that both doses and radiosensitivities in human populations exposed to ionizing radiation are random variables, modeled by lognormal density functions. Here, radiosensitivity is defined as the dose limit up to which radiation damage can be repaired by the cellular repair systems, in short, the repair capacity. Monte Carlo simulation is used to generate N pairs of individual doses and repair capacities. Radiation damage occurs whenever the dose exceeds the related repair capacity. The rate of radiation damage is the number of damages, divided by the number N of pairs. Monte Carlo simulation is conducted for a sufficient number of ascending median doses. The shape of the dose-response relationship is determined by regression of damage rates on mean dose. Regression with a cumulative lognormal distribution function yields a perfect fit to the data. Acceptance of the hypothesis means that studies of adverse health effects following in-utero exposure to low doses of ionizing radiation should not be discarded primarily because they contradict the concept of a threshold dose for teratogenic effects.

Cover up and cancer risk assessment: Prominent US scientists suppressed evidence to promote adoption of LNT.

This paper reports that William Russell, Oak Ridge National Laboratory (ORNL), conducted a large-scale lifetime study from 1956 to 1959 showing that exposure of young adult male mice to a large dose of acute X-rays had no treatment effects on male and female offspring concerning longevity or the frequency, severity, or age distribution of neoplasms and other diseases. Despite the scientific, societal and crucial timing significance of the study, Russell did not publish the findings for almost 35 years, nor did he inform governmental advisory committees, thereby significantly biasing decisions made during this period which supported the adoption of LNT for risk assessment. Of further significance, Arthur Upton, an ORNL colleague of Russell during this study and later Director of the US National Cancer Institute (NCI), was also fully knowledgeable of this study, its findings and its negative impact on the acceptance of LNT. Upton later worked along with Russell to publish these data (i.e., Cosgrove et al., 1993) to dispute the case-specific claim that children developed cancer because of the radiation exposure of their fathers as workers at the Sellafield nuclear plant. Thus, while Russell's data were available, but were not used to challenge the key radiation and leukemia paper of Edward B. Lewis, (1957) when LNT was being adopted by regulatory agencies, they were used in a major trial in the United Kingdom (UK) for the client (i.e., British Nuclear Fuels Plc) that hired Upton. While the duplicity of Russell's and Upton's actions is striking, the key finding of the present paper is that Russell and Upton intentionally orchestrated and sustained an LNT cover up during the key period of LNT adoption by regulatory agencies, thereby showing an overwhelming bias to enhance the adoption of LNT.

Application of 233 nm far-UVC LEDs for eradication of MRSA and MSSA and risk assessment on skin models.

A newly developed UVC LED source with an emission wavelength of 233 nm was proved on bactericidal efficacy and skin tolerability. The bactericidal efficacy was qualitatively analysed using blood agar test. Subsequently, quantitative analyses were performed on germ carrier tests using the MRSA strain DSM11822, the MSSA strain DSM799, S. epidermidis DSM1798 with various soil loads. Additionally, the compatibility of the germicidal radiation doses on excised human skin and reconstructed human epidermis was proved. Cell viability, DNA damage and production of radicals were assessed in comparison to typical UVC radiation from discharge lamps (222 nm, 254 nm) and UVB (280-380 nm) radiation for clinical assessment. At a dose of 40 mJ/cm2, the 233 nm light source reduced the viable microorganisms by a log10 reduction (LR) of 5 log10 levels if no soil load was present. Mucin and protein containing soil loads diminished the effect to an LR of 1.5-3.3. A salt solution representing artificial sweat (pH 8.4) had only minor effects on the reduction. The viability of the skin models was not reduced and the DNA damage was far below the damage evoked by 0.1 UVB minimal erythema dose, which can be regarded as safe. Furthermore, the induced damage vanished after 24 h. Irradiation on four consecutive days also did not evoke DNA damage. The radical formation was far lower than 20 min outdoor visible light would cause, which is classified as low radical load and can be compensated by the antioxidant defence system.

Dose-dependent Transmissibility of Chromosome Aberrations at First Mitosis after Exposure to Gamma Rays. I. Modeling and Implications Related to Risk Assessment.

The relationship between certain chromosomal aberration (CA) types and cell lethality is well established. On that basis we used multi-fluor in situ hybridization (mFISH) to tally the number of mitotic human lymphocytes exposed to graded doses of gamma rays that carried either lethal or nonlethal CA types. Despite the fact that a number of nonlethal complex exchanges were observed, the cells containing them were seldom deemed viable, due to coincident lethal chromosome damage. We considered two model variants for describing the dose responses. The first assumes independent linear-quadratic (LQ) dose response shapes for the yields of both lethal and nonlethal CAs. The second (simplified) variant assumes that the mean number of nonlethal CAs per cell is proportional to the mean number of lethal CAs per cell, meaning that the shapes and magnitudes of both aberration types differ only by a multiplicative proportionality constant. Using these models allowed us to assemble dose response curves for the frequency of aberration-bearing cells that would be expected to survive. This took the form of a joint probability distribution for cells containing ≥1 nonlethal CAs but having zero lethal CAs. The simplified second model variant turned out to be marginally better supported than the first, and the joint probability distribution based on this model yielded a crescent-shaped dose response reminiscent of those observed for mutagenesis and transformation for cells "at risk" (i.e. not corrected for survival). Among the implications of these findings is the suggestion that similarly shaped curves form the basis for deriving metrics associated with radiation risk models.

Environmental and industrial developments in radiation cataractogenesis.

PURPOSE: This review discusses recent developments in our understanding of biological and physiological mechanisms underlying radiation cataractogenesis. The areas discussed include effects of low-dose exposures to the lens including potential relevance of non-targeted effects, the development of new personal-protective equipment (PPE) and standards in clinical and nuclear settings motivated by the updated ICRP recommendations to mitigate exposures to the lens of the eye. The review also looks at evidence from the field linking cataracts in birds and mammals to low dose exposures. CONCLUSIONS: The review suggests that there is evidence that cataractogenesis is not a tissue reaction (deterministic effect) but rather is a low dose effect which shows a saturable dose response relationship similar to that seen for non-targeted effects in general. The review concludes that new research is needed to determine the dose response relationship in environmental studies where field data are contradictory and lab studies confined to rodent models for human exposure studies.

Quantitative Bias Analysis of the Association between Occupational Radiation Exposure and Ischemic Heart Disease Mortality in UK Nuclear Workers.

The scientific question of whether protracted low-dose or low-dose-rate exposure to external radiation is causally related to the risk of circulatory disease continues to be an important issue for radiation protection. Previous analyses of a matched case-control dataset nested in a large cohort of UK nuclear fuel cycle workers indicated that there was little evidence that observed associations between external radiation dose and ischemic heart disease (IHD) mortality risk [OR = 1.35 (95% CI: 0.99-1.84) for 15-year-lagged exposure] could alternatively be explained by confounding from pre-employment tobacco smoking, BMI or blood pressure, or from socioeconomic status or occupational exposure to excessive noise or shiftwork. To improve causal inference about the observed external radiation dose and IHD mortality association, we estimated the potential magnitude and direction of non-random errors, incorporated sensitivity analyses and simulated bias effects under plausible scenarios. We conducted quantitative bias analyses of plausible scenarios based on 1,000 Monte Carlo samples to explore the impact of exposure measurement error, missing information on tobacco smoking, and unmeasured confounding, and assessed whether observed associations were reliant on the inclusion of specific matched pairs using bootstrapping with 10% of matched pairs randomly excluded in 1,000 samples. We further explored the plausibility that having been monitored for internal exposure, which was an important confounding factor in the case-control analysis for which models were adjusted, was indeed a confounding factor or whether it might have been the result of some form of selection bias. Consistent with the broader epidemiological evidence-base, these analyses provide further evidence that the dose-response association between cumulative external radiation exposure and IHD mortality is non-linear in that it has a linear shape plateauing at an excess risk of 43% (95% CI: 7-92%) on reaching 390 mSv. Analyses of plausible scenarios of patterns of missing data for tobacco smoking at start of employment indicated that this resulted in relatively little bias towards the null in the original analysis. An unmeasured confounder would have had to have been highly correlated (rp > 0.60) with cumulative external radiation dose to importantly bias observed associations. The confounding effect of "having been monitored for internal dose" was unlikely to have been a true confounder in a biological sense, but instead may have been some unknown factor related to differences over time and between sites in selection criteria for internal monitoring, possibly resulting in collider bias. Plausible patterns of exposure measurement error negatively biased associations regardless of the modeled scenario, but did not importantly change the shape of the observed dose-response associations. These analyses provide additional support for the hypothesis that the observed association between external radiation exposure and IHD mortality may be causal.

Impact of low-dose computed tomography for lung cancer screening on lung cancer surgical volume: The urgent need in health workforce education and training.

ABSTRACT: This study aimed to investigate the time trend variation in the surgical volume and prognostic outcome of patients with lung cancer after the gradual prolonged implementation of a low-dose computed tomography (LDCT) lung cancer screening program.Using the hospital-based cancer registry data on number of patients with lung cancer and deaths from 2008 to 2017, we conducted a retrospective study using a hospital-based cohort to investigate the relationship between changes in lung cancer surgical volume, the proportion of lung-sparing surgery, and prolonged prognostic outcomes after the gradual implementation of the LDCT lung cancer screening program in recent years.From 2008 to 2017, 3251 patients were diagnosed with lung cancer according to the hospital-based cancer registry. The 5-year mortality rate decreased gradually from 83.54% to 69.44% between 2008 and 2017. The volume of total lung cancer surgical procedures and proportion of lung-sparing surgery performed gradually increased significantly from 2008 to 2017, especially from 2014 to 2017 after implementation of a large volume of LDCT lung cancer screening examinations. In conclusion, our real-world data suggest that there will be an increase in cases of operable early-stage lung cancers, which in turn will increase the surgical volume and proportion of lung-sparing surgery, after the gradual implementation of the LDCT lung cancer screening program in recent years. These findings suggest the importance of a successful national policy regarding LDCT screening programs, regulation of shortage of thoracic surgeons, thoracic radiologist workforce training positions, and education programs.

Dose Coefficient Calculation for Use in Dosimetry Assessment of a Fission-Based Weapon.

In the event of a fission-based weapon or improvised nuclear device (IND) detonation, dose coefficients can be harnessed to provide dose assessments for defense, emergency preparedness, and consequence management, as well as to prospectively inform the assessment of radiation biomarkers and development of medical prophylaxis countermeasures for defense and homeland security stakeholders and decision-makers. Although dose coefficients have previously been calculated for this group, they would apply specifically to the studied population, the 1945 Japanese cohort, after which their anthropomorphic computational phantoms were modeled. For this reason, applications to other populations may be limited, and instead, an assessment of a more standardized population is desired. We employed a series of computational human phantoms representing international reference individuals: UF/NCI voxel phantom series containing newborn, 1-, 5-, 10-, 15-, and 35-year-old males and females. Irradiation of the phantoms was simulated using the Monte Carlo N-Particle transport code to determine organ dose coefficients under four idealized irradiation geometries at three distances from the detonation hypocenter at Hiroshima and Nagasaki using DS02 free-in-air prompt neutron and photon fluence spectra. Through these simulations, age-specific dose coefficients were determined for individual organs. Various articulated PIMAL stylized phantoms were simulated as well to estimate the effect of body posture on dose coefficients and determine the effect of posture on dosimetric estimation and reconstruction. Results additionally demonstrate that 137Cs and the Watt fission spectra are not ideal general surrogate sources for fission weapons, which may be considered for experimental testing of medical countermeasures. Supplementary data provided tabulates the compilation of organ dose-rate coefficients in this study.

Monte Carlo-based calculation of nano-scale dose enhancement factor and relative biological effectiveness in using different nanoparticles as a radiosensitizer.

INTRODUCTION: Nowadays, some nanoparticles (NPs) are known and used as radiosensitizers in radiotherapy and radiobiology, due to their desired biological, physical, and chemical effects on cells. This study aimed to evaluate and compare the dose enhancement factor (DEF) and the biological effectiveness of some common NPs through EGSnrc and MCDS Monte Carlo (MC) simulation codes. MATERIALS AND METHODS: To evaluate considered NPs' DEF, a single NP with 50 nm diameter was simulated at the center of concentric spheres. NP irradiations were done with 30, 60, and 100 keV photon energies. The secondary electron spectra were scored at the surface of considered NPs, and the dose values were scored at surrounding water-filled spherical shells which were distributed up to 4000 nm from the NP surface. The electron spectra were used in the MCDS code to obtain different initial DNA damages for the calculation of enhanced relative biological effectiveness (eRBE). RESULTS: By decreasing the photon energy, an increment of DEF was seen for all studied NPs. The maximum DEF at 30, 60, and 100 keV photon energies were respectively related to silver (Ag), gadolinium (Gd), and bismuth (Bi) NPs. The maximum double-strand break (DSB) related (eRBEDSB) values for the 30 keV photon belonged to Ag, while BiNPs showed the maximum values at other photon energies. The minimum eRBEDSB values were also related to iron (Fe) NPs at the entire range of studied photon energies. CONCLUSIONS: The compared nanoscale physical and biological results of our study can be helpful in the selection of optimum NP as a radiosensitizer in future radiobiological studies. Bi, gold (Au), Ag, and platinum (Pt) NPs had great potential, respectively, as radiosensitizers relative to the other studied NPs.