Radiobiological Research Articles

Milestones 2.0 for Competency-Based Assessment of Radiation Oncology Medical Residents

<h3>Purpose/Objective(s)</h3> Radiation Oncology Milestones 1.0 was developed in 2011 to standardize competency-based assessment of radiation oncology medical residents using the Accreditation Council of Graduate Medical Education's (ACGME) 6 core competencies. However, its implementation across programs varied because the language was too complex, the sub-competencies lacked a clear progression between levels, and there were no directions for standardized use across programs. We hypothesized that the milestones could be revised to simplify the language, clarify expectations, and describe sequential clinical skill development while providing more guidance on implementation. <h3>Materials/Methods</h3> The ACGME assembled a 9-member volunteer working group to compose Milestones 2.0 for Radiation Oncology using a modified Delphi method consisting of multiple asynchronous small-group meetings interspersed with four web-based synchronous whole-group meetings until consensus was reached for each competency. New sub-competencies retained the ordinal 5-level scale from Milestones 1.0 where level 1 reflects expectations at the beginning of the post-graduate 2-year, level 4 describes competencies expected at graduation, and level 5 describes features displayed by the top 10% of residents. Additionally, the committee composed a supplemental guide that expounds on the implementation of Milestones 2.0. <h3>Results</h3> In Milestones 2.0, all sub-competencies were simplified by limiting the criteria for each level to a maximum of three descriptors and requiring the sub-competencies to chart a clear progression of advancing resident development across levels. Research was omitted from all competencies since it did not reflect a natural progression in clinical skills. Within the core competencies, disease-site specific Patient Care sub-competencies were revised to describe patient-centric care. For Medical Knowledge, Radiation Biology and Physics were grouped into Applied Sciences and Evidence-Based Foundations of Radiation Oncology was added. The descriptions for the remaining sub-competencies were condensed. The supplemental guide includes examples of different levels of resident competence and encourages the addition of program-specific examples to create a shared model among evaluators. <h3>Conclusion</h3> Milestones 2.0 simplifies competency-based assessment of radiation oncology medical residents, emphasizes skills needed for patient care, and provides additional guidance on implementation for programs. As it is put into practice in July 2022, we will continue to identify challenges with implementation and to design improvements.

Assessment of Medical Student Research Mentorship Based on Publications in ASTRO Journals

<h3>Purpose/Objective(s)</h3> Mentored research opportunities often stimulate medical student (MS) interest in a particular field and help them to be competitive residency applicants. Many MSs pursue at least one research project during medical school. According to the Association of American Medical Colleges faculty roster there are approximately 1,800 radiation oncology (RO) faculty at US MD-granting medical schools; however, little is known about whether radiation oncologists are providing adequate research opportunities to MSs who are potentially interested in the specialty. We hypothesize that relatively few academic RO faculty mentor MSs in research, and the minority of publications in American Society for Radiation Oncology (ASTRO) journals will have MS co-authors. <h3>Materials/Methods</h3> Data for this study derived from a review of the byline and abstract of all 1,785 scientific articles (i.e., clinical, basic science, training/education) and case reports published from 2019-2021 in The International Journal of Radiation Oncology, Biology, and Physics (IJROBP), Practical Radiation Oncology (PRO), and Advances in Radiation Oncology (ARO). Review, editorial, and correspondence article types were excluded. MS authors were defined as individuals affiliated with a medical school but lacking an MD, DO, or PhD degree. The primary faculty mentor was defined as the senior (last) author. Information related to article type, methods, institution, and author position was recorded. Descriptive statistics and Chi square test were used where appropriate. <h3>Results</h3> A total of 105 of 1,785 articles (6%) included a MS author, among which 72 (69%) were clinical, 13 (11%) training/education, 12 (11%) case reports, and 8 (8%) basic science. MS authors were more common for publications in ARO (9%) than PRO (6%) or IJROBP (4%, <i>p</i> = 0.002). Thirty-eight (32%) MSs were first author, 26 (22%) second author, and 55 (46%) third author or beyond. There were 88 unique faculty mentors for these articles, with 10 mentors (11%) on 2 or more MS publications, and 57 mentors (64.7%) sharing the same institution as the MS. The median number of articles per mentor institution was 1 (interquartile range 1-2), and the mentor institutions in the upper quartile in terms of number of MS publications accounted for 53 (50.5%) of all MS publications. <h3>Conclusion</h3> Over the past 3 years, a small fraction of publications in ASTRO journals included MS authors, with mentorship disproportionately from a small number of academic faculty at select institutions. Though RO faculty may mentor MSs on projects published in other journals, efforts to more broadly encourage academic RO faculty to offer MSs research opportunities on RO-related projects may help stimulate more interest in RO, and reverse the recent trend of fewer residency applicants.

Oncology wounds – recommendations for care based on multidisciplinary cooperation

Oncology wounds and wounds of other etiology are rare but serious complications, which significantly impair patients quality of life. Preventive and curative interventions and education of healthcare personnel and patients reduce the risk of either their occurrence or their impact and consequences. A working group of authors from professional groups (the Supportive Care Group of the Czech Society for Oncology, the Czech Society for Wound Healing, the Society for Radiation Oncology, Biology and Physics, and the Czech Nurses Association) prepared recommendations for care. A comprehensive approach to the treatment of oncological wounds, including symptomatic treatment of associated healing complications, prevention, early detection, interdisciplinary cooperation and education are essential to deal with wounds related to chemotherapy administration, radiotherapy and oncological treatment in general. The proper choice of local care products and the eventuality of active oncological treatment are important elements of care in ulcerating tumors.A basic summary of recommended interventions to prevent and treat oncology wounds in daily practice, defined based on expert societies guidelines, trials and literature data, proven practice and on the consensus opinions of the authors group members. The recommended procedures contribute to the reduction of the development, severity and consequences of oncological wounds and wounds of other etiology in oncological patients.

Development and validation of an indigenous, radiobiological model-based tumor control probability and normal tissue complication probability estimation software for routine plan evaluation in clinics.

Development and validation of a simple and convenient computational program in MATLAB environment for estimating the tumor control probability (TCP) and the normal tissue complication probability (NTCP), as a decision support system for routine plan evaluation. We developed an in-house software using MATLAB 2016b (Mathworks) for estimating TCP and NTCP named as RBMODELV1. The program contains Niemierko free equivalent uniform dose (EUD) program code provided in authors research article. For rest of radiobiological (RB) models in the software separate coding is performed. The program accepts cumulative dose-volume histogram file in (.txt) format containing two columns dose and volume. A set of two RB parameters were prepared, default and user-dependent in excel sheet named as RBDATA. We cross-validated results of RBMODELV1 software with BioSuite software for Poisson's TCP model and Lyman-Kutcher-Burman (LKB) model. A set of total 20 patient's data of head and neck site took under study and respective TCP and NTCP calculated by all the RB models and compared. This is the first study in which we tried to establish correlation between the mean doses (EUD) received by parallel structure (parotid gland and oral cavity) and predicted percentage of NTCP values. It is found that mean dose in the range of 35-40 Gy for parotid gland can result in more than 50% NTCP predicted by all four RB models. Similarly oral cavity receiving mean dose in the range of 53-58 Gy can results in more than 35% NTCP predicted by all the four models. There is <3% variation observed between TCP calculated by BioSuite and RBMODELV1 software and <4% variation observed between predicted NTCP for parotid gland and oral cavity OAR from LKB model by both the software. We created simple software RBMODELV1 which can be used as a research tool as well as decision support system.

Academic program recommendations for graduate degrees in medical physics: AAPM Report No. 365 (Revision of Report No. 197).

Academic program recommendations for graduate degrees in medical physics: AAPM Report No. 365 (Revision of Report No. 197).

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.

Validation of a High-Throughput Dicentric Chromosome Assay Using Complex Radiation Exposures.

Validation of biodosimetry assays is routinely performed using primarily orthovoltage irradiators at a conventional dose rate of approximately 1 Gy/min. However, incidental/ accidental exposures caused by nuclear weapons can be more complex. The aim of this work was to simulate the DNA damage effects mimicking those caused by the detonation of a several kilotons improvised nuclear device (IND). For this, we modeled complex exposures to: 1. a mixed (photons + IND-neutrons) field and 2. different dose rates that may come from the blast, nuclear fallout, or ground deposition of radionuclides (ground shine). Additionally, we assessed whether myeloid cytokines affect the precision of radiation dose estimation by modulating the frequency of dicentric chromosomes. To mimic different exposure scenarios, several irradiation systems were used. In a mixed field study, human blood samples were exposed to a photon field enriched with neutrons (ranging from 10% to 37%) from a source that mimics Hiroshima's A-bomb's energy spectrum (0.2-9 MeV). Using statistical analysis, we assessed whether photons and neutrons act in an additive or synergistic way to form dicentrics. For the dose rates study, human blood was exposed to photons or electrons at dose rates ranging from low (where the dose was spread over 32 h) to extremely high (where the dose was delivered in a fraction of a microsecond). Potential effects of cytokine treatment on biodosimetry dose predictions were analyzed in irradiated blood subjected to Neupogen or Neulasta for 24 or 48 h at the concentration recommended to forestall manifestation of an acute radiation syndrome in bomb survivors. All measurements were performed using a robotic station, the Rapid Automated Biodosimetry Tool II, programmed to culture lymphocytes and score dicentrics in multiwell plates (the RABiT-II DCA). In agreement with classical concepts of radiation biology, the RABiT-II DCA calibration curves suggested that the frequency of dicentrics depends on the type of radiation and is modulated by changes in the dose rate. The resulting dose-response curves suggested an intermediate dicentric yields and additive effects of photons and IND-neutrons in the mixed field. At ultra-high dose rate (600 Gy/s), affected lymphocytes exhibited significantly fewer dicentrics (P < 0.004, t test). In contrast, we did not find the dose-response modification effects of radiomitigators on the yields of dicentrics (Bonferroni corrected P > 0.006, ANOVA test). This result suggests no bias in the dose predictions should be expected after emergency cytokine treatment initiated up to 48 h prior to blood collection for dicentric analysis.

Sterility of Cydia pomonella by X ray irradiation as an alternative to gamma radiation for the sterile insect technique.

The codling moth Cydia pomonella is a major pest of global significance impacting pome fruits and walnuts. It threatens the apple industry in the Loess Plateau and Bohai Bay in China. Sterile insect technique (SIT) could overcome the limitations set by environmentally compatible area-wide integrated pest management (AW-IPM) approaches such as mating disruption and attract-kill that are difficult to suppress in a high-density pest population, as well as the development of insecticide resistance. In this study, we investigated the effects of X-ray irradiation (183, 366, 549 Gy) on the fecundity and fertility of a laboratory strain of C. pomonella, using a newly developed irradiator, to evaluate the possibility of X-rays as a replacement for Cobalt60 (60Co-γ) and the expanded future role of this approach in codling moth control. Results show that the 8th-day is the optimal age for irradiation of male pupae. The fecundity decreased significantly as the dosage of radiation increased. The mating ratio and mating number were not influenced. However, treated females were sub-sterile at a radiation dose of 183 Gy (20.93%), and were almost 100% sterile at a radiation dose of 366 Gy or higher. Although exposure to a radiation dose of 366 Gy resulted in a significant reduction in the mating competitiveness of male moths, our radiation biology results suggest that this new generation of X-ray irradiator has potential applications in SIT programs for future codling moth control.

Responses of hematopoietic cells after ionizing-irradiation in anemic adult medaka (Oryzias latipes)

Purpose Hematopoietic tissues of vertebrates are highly radiation sensitive and the effects of ionizing radiation on the hematopoiesis have been studied in mammals and teleosts for decades. In this study, radiation responses in the kidney, the main hematopoietic organ in teleosts, were investigated in Japanese medaka (Oryzias latipes), which has been a model animal and a large body of knowledge has been accumulated in radiation biology. Methods Kidney, the main hematopoietic tissue of adult medaka fish, was locally irradiated using proton and carbon ion beams irradiation system of Takasaki Ion Accelerator for Advanced Radiation Application (TIARA), QST, and the effects on peripheral blood cells and histology of the kidney were investigated. Results When only kidneys were locally irradiated with proton or carbon ion beam (15 Gy), the hematopoietic cells in the irradiated kidney and cell density in the peripheral blood decreased 7 days after the irradiation in the same manner as after the whole-body irradiation with γ-rays (15 Gy). These results demonstrate that direct irradiation of the hematopoietic cells in the kidney induced cell death and/or cell cycle arrest and stopped the supply of erythroid cells. Then, the cell density in the peripheral blood recovered to the control level within 4 days and 7 days after the γ-ray and proton beam irradiation (15 Gy), respectively, while the cell density in the peripheral blood did not recover after the carbon ion beam irradiation (15 Gy). The hematopoietic cells in the irradiated kidneys temporarily decreased and recovered to the control level within 21 days after the γ-ray or proton beam irradiation (15 Gy), while it did not recover after the carbon ion beam irradiation (15 Gy). In contrast, the recovery of the cell density in the peripheral blood delayed when anemic medaka were irradiated 1 day after the administration of phenylhydrazine. With and without γ-ray irradiation, a large number of hematopoietic cells was still proliferating in the kidney 7 days after the anemia induction. Conclusions The results obtained strongly suggest that the hematopoietic stem cells in medaka kidney prioritize to proliferate and increase peripheral blood cells to eliminate anemia, even when they are damaged by high-dose irradiation.

A comparative analysis of powder ENDOR spectra of aromatic and aliphatic radicals by exact and 1st order simulation

Exact and perturbation methods were employed in simulations of powder ENDOR spectra to obtain the anisotropic hyperfine ( hfc ) and nuclear quadrupole ( nqc ) coupling constants of certain organic radicals of interest in fundamental research and in applications in radiation research, surface chemistry and biophysics. The principal hfc values of the ring protons and methyl substituents for several aromatic cations trapped in disordered matrices might be more accurate than those previously reported using regular EPR. Only one of the earlier assignments of the naphthalene cation spectrum was in acceptable agreement with the simulations. The proton couplings at the β-position of alkyl radicals were deduced by simulations while the spectrum due to α-couplings with appreciable anisotropy was weak. Accurate simulation of the 14 N (I = 1) spectra in bio-radicals was obtained by adjustment of the relative orientation of the principal hfc and nuclear quadrupole coupling ( nqc ) tensors as well as the principal values. Adjustment of the excitation width parameter employed in the software was also required in a few cases to improve the agreement with the experimental spectra. The hfc patterns due to matrix nuclei ( 1 H and 7 Li) around the radicals of X-irradiated samples were simulated to elucidate the nature of the trapping sites in materials used for EPR dosimetry. ENDOR simulation programs known to us are presented in an Appendix. The performance of the ENDORF2 program used in previous works was examined by comparison with exact treatment. Input and output examples, source and executable codes used in this work can be downloaded at https://github.com/EndorF2/Simulation .

Modeling the Lunar Radiation Environment: A Comparison Among FLUKA, Geant4, HETC‐HEDS, MCNP6, and PHITS

AbstractRadiation transport codes have been an increasingly important tool for studying the space radiation environment, which includes high‐energy and high‐nuclear‐charge particles. The unique advantage of transport models lies in covering a wider range of particles, energies, and angles than would be attainable in a laboratory or measurable by an instrument. However, since there are several transport codes developed by different teams that have contributed heavily to the literature, differences are expected between such codes. In this work, we use five such radiation transport codes (FLUctuating KAscade, GEometry ANd Tracking, High‐Energy Transport Code‐Human Exploration and Development in Space, Monte Carlo N‐Particle, and Particle and Heavy Ion Transport code System) to study the radiation environment near the Moon, specifically the lunar “albedo” radiation, which is the radiation emitted by the lunar surface through interactions with incident galactic cosmic rays and solar energetic particles. The primary goal of this paper is to provide a general characterization of the lunar albedo radiation and to find the areas where the modeled transport codes agree and disagree by using almost identical input parameters. The results of this work show overall good agreement between the codes. However, some areas of discrepancies exist that are reported herein. Thus, this paper equips the space weather and radiation biology communities with a comparison between popular radiation transport models applied to lunar albedo radiation. The overall agreement and, in some cases, discrepancies between these transport codes provide fundamental insight necessary for assessing code reliability and identifying where further study and improvements are needed to advance our understanding of lunar albedo radiation.

Accelerating space radiation countermeasure development through drug repurposing

The discovery of safe and effective radiation countermeasures (MCM) for long-duration spaceflight is challenging due to the complexity of the space radiation biology and high safety requirements. There are few if any clinically-validated molecular targets for this use case, and preclinical models have several known limitations. These challenges make the evaluation of existing FDA-approved drugs for this indication, or drug repurposing, an attractive strategy to accelerate space radiation countermeasure development. Drug repurposing offers several advantages over de novo drug discovery including established manufacturing methods, human clinical safety data, and well-understood dosing and pharmacokinetic considerations. There are limitations working with a fixed set of possible candidate compounds, but some properties of repurposed drugs can be tailored for well-defined new indications through reformulation and development of drug combinations. Drug repurposing is thus an attractive strategy for mitigating the high risks and costs of drug development and delivering new countermeasures to protect human from space radiation in long-term missions.

Abstract SY43-02: Adapting clinical radiation therapy to immune checkpoint blockade

Abstract Focal radiation therapy has demonstrated to elicit inflammatory and immune responses that contribute to cancer immunosurveillance, but may also have unwanted systemic effects. The application of ionizing radiation to cancer, which is the basis for the field of radiation oncology, has evolved to define and exploit the therapeutic window between radiation cytocidal effects in tumors versus those in normal tissue. The original standardization of specific dose-fractionation regimens reflected the results of decades of empirical experience to find the best balance between local control of the irradiated cancer and the mitigation of risk for acute and late sequelae in the exposed normal tissues. More than a century of research in radiation biology has elucidated how radiation damage recruits a classical inflammation response, activates pathways to repair tissues through scavenging of cellular debris and canonical wound repair mechanisms that aim at recovering tissue integrity. Intrinsic to this process is a robust dampening of immunogenic signals, common to those associated with wound repair, to prevent triggering of auto-immune rejections of inflamed tissues. At the same time, radiation has proimmunogenic effects, that recruit both the innate arm of the immune system (acute induction of IFN pathways) and the adaptive arm, through radiation-induced neoepitopes and enhanced cross presentation. Strategies to uncouple these opposite effects are the focus of research efforts in multiple radiation biology laboratories, worldwide. The emergence of modern cancer immunotherapy offers the opportunity to further dissect such strategies. Recent evidence suggest a new role for focal radiotherapy, to partnering and synergize with immune checkpoint blockade (ICB). Evidence is emerging both preclinically and in the clinical setting that optimal integration of radiotherapy with the available immune modifiers might require changes in standard radiation oncology practices. Variables like the type of treatment fields, the inclusion of draining nodal stations, the degree of exposure of circulating immune cells, the type of dose-fractionation and the timing of radiotherapy during ICB all can affect the success of immunoradiotherapy combinations. Hence, defining the parameters for adapting classic radiation therapy to best integrate with ICB remains a fundamental area of investigation, as it is integral to a successful partnership with immunotherapy. Citation Format: Silvia C. Formenti. Adapting clinical radiation therapy to immune checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY43-02.

Cell Fate following Irradiation of MDA-MB-231 and MCF-7 Breast Cancer Cells Pre-Exposed to the Tetrahydroisoquinoline Sulfamate Microtubule Disruptor STX3451.

A tetrahydroisoquinoline (THIQ) core is able to mimic the A and B rings of 2-methoxyestradiol (2ME2), an endogenous estrogen metabolite that demonstrates promising anticancer properties primarily by disrupting microtubule dynamic instability parameters, but has very poor pharmaceutical properties that can be improved by sulfamoylation. The non-steroidal THIQ-based microtubule disruptor 2-(3-bromo-4,5-dimethoxybenzyl)-7-methoxy-6-sulfamoyloxy-1,2,3,4-tetrahydroisoquinoline (STX3451), with enhanced pharmacokinetic and pharmacodynamic profiles, was explored for the first time in radiation biology. We investigated whether 24 h pre-treatment with STX3451 could pre-sensitize MCF-7 and MDA-MB-231 breast cancer cells to radiation. This regimen showed a clear increase in cytotoxicity compared to the individual modalities, results that were contiguous in spectrophotometric analysis, flow cytometric quantification of apoptosis induction, clonogenic studies and microscopy techniques. Drug pre-treatment increased radiation-induced DNA damage, with statistically more double-strand (ds) DNA breaks demonstrated. The latter could be due to the induction of a radiation-sensitive metaphase block or the increased levels of reactive oxygen species, both evident after compound exposure. STX3451 pre-exposure may also delay DNA repair mechanisms, as the DNA damage response element ataxia telangiectasia mutated (ATM) was depressed. These in vitro findings may translate into in vivo models, with the ultimate aim of reducing both radiation and drug doses for maximal clinical effect with minimal adverse effects.

Electron flash-RT program in clinical setting for human translation.

e13596 Background: A FLASH-RT program was established at Dartmouth-Hitchcock Medical Center in minimally-modified clinical setting by joint efforts of biomedical engineering, radiation oncology, radiation biology and medical physics teams. Various projects on dosimetry, chemical sensing, molecular profiling, software/hardware development, and translational studies have been conducted. The aim is to share logistical considerations and experience on running a FLASH-RT program to support institution-wide academic activities with an ultimate goal of treating human patients with FLASH-RT in 2022. Methods: A linac was converted in the clinical setting by qualified engineers to deliver an ultra-high dose rate (UHDR) electron beam. Routine safety and dosimetry checks were done by physicists for every reversible conversion. Long-term record-keeping and retrospective surveys were carried out to demonstrate the feasibility, safety, stability and accuracy of this dual-purpose (FLASH and conventional RT) approach. Comprehensive failure mode and effects analysis (FMEA) has been completed to systematically evaluate safety related considerations. A treatment planning system (TPS) has been developed in Varian Eclipse to facilitated comparative studies. The FLASH-capable linac has been utilized as shared resource to support institution-wide academic activities as well as normal clinical treatments. Results: With its safety (no accident or FLASH-related malfunction), flexibility (&gt; 100 conversions in 2 years), reliability (̃6000 hours in flash mode and ̃5x105 Gy accumulative dose delivered at isocenter) and accuracy (̃5% conversion-to-conversion variations) demonstrated by commissioning, long-term user experience and comprehensive FMEA analysis, the FLASH-RT platform has been actively utilized for researches in six major categories 1) FLASH beam dosimetry; 2) real-time beam delivery monitoring and control; 3) oximetry and chemical sensing; 4) preclinical/translational small/large animal treatment with tumor control and normal tissue complication endpoints, 5) treatment plan and delivery optimization; 6) the design of phase I/II trials. Key findings in each category will be reported. Conclusions: A FLASH-RT program in clinical setting is established at Dartmouth with joint efforts, promoting collaborative projects to advance FLASH-RT to clinical treatment. The system has been reliably utilized for over two years for mechanistic as well as translational studies and support a phase I/II trial treating cutaneous lymphoma with eFLASH-RT.

Clinical Trial in a Dish for Space Radiation Countermeasure Discovery

NASA aims to return humans to the moon within the next five years and to land humans on Mars in a few decades. Space radiation exposure represents a major challenge to astronauts’ health during long-duration missions, as it is linked to increased risks of cancer, cardiovascular dysfunctions, central nervous system (CNS) impairment, and other negative outcomes. Characterization of radiation health effects and developing corresponding countermeasures are high priorities for the preparation of long duration space travel. Due to limitations of animal and cell models, the development of novel physiologically relevant radiation models is needed to better predict these individual risks and bridge gaps between preclinical testing and clinical trials in drug development. “Clinical Trial in a Dish” (CTiD) is now possible with the use of human induced pluripotent stem cells (hiPSCs), offering a powerful tool for drug safety or efficacy testing using patient-specific cell models. Here we review the development and applications of CTiD for space radiation biology and countermeasure studies, focusing on progress made in the past decade.

The interaction of oxidative stress with MAPK, PI3/AKT, NF-κB, and DNA damage kinases influences the fate of γ-radiation-induced bystander cells

Oxidative stress is associated with the induction of a plethora of effects on cellular macromolecules and signaling cascades. The onset of oxidative imbalance characterizes irradiated cells. The present study investigates the effects of ionizing radiation on oxidative stress induction in bystander cells and their interactions with critical cell signaling mediators. The effect of irradiated cell-conditioned medium (ICCM) from γ-irradiated hepatocellular carcinoma (HepG2) cells were studied in bystander HepG2 and normal liver (BRL-3A) cells at early (1 h, 2 h) and later (24 h) time points post-irradiation. Although ROS generation and lipid peroxidation showed the highest effects in both bystander cell groups at the early time points, antioxidant enzymes superoxide dismutase and catalase showed the lowest activity. Oxidative stress was persistent up to 24 h, but the highest level was seen in 1 h ICCM treated 8By cells. Although the levels of all pro-survival signaling factors (p-PI3K, p-Akt, p-p38MAPK, p-JNK, and p-NFκB) increased in bystander HepG2 cells, they showed a significant decrease in bystander BRL-3A cells. JAK2-STAT3 activation, however, was reduced only in BRL-3A cells, with no effect in HepG2 cells. However, in both bystander cell groups, activation of DNA damage sensors ATM, ATR, and cell cycle inhibitor p21 increased. Elevated ROS levels down-regulated the activation of PI3K, Akt, JNK, and NF-κB in BRL-3A cells but enhanced the activation of ATM and p21. In contrast, in HepG2 cells, increased ROS level elevated the activation of PI3K, JNK, p38MAPK, NF-κB with no effect on p-ATM or p21. ROS differentially influenced the interactions between the signaling mediators in the bystander cells. p-ATR levels, although increased in both bystander cell groups, showed no association with other factors. ICCM from the same HepG2 cells differently affected signaling factors in two groups of cells, highlighting the critical significance of the study in the field of radiation biology.

Advances in Radiation Oncology: Current Status and Future Directions in India.

Radiation therapy is one of the core components of the comprehensive cancer care. Several new advancements in the radiation physics, radiation biology, and technical upgradation have led us in to a new era of radiation oncology. The access to quality radiation therapy treatment however remains a concern, and this mini-review emphasizes on these issues and also focuses on the future directions for radiation oncology in India.

Establishing bilateral modulation of radiation induced redox damage via biocatalytic single atom engineering at Au clusters

Modulation of radiation biological process at atomic and molecular level is closely related to biocatalytic process, redox biology and multisystem inflammation. Thus, it is necessary to clarify the exact relationship between the biocatalytic process and radiation biology, and further establish the corresponding intrinsic mechanism. In this work, we employed a serial of single atom substitutional gold clusters, which show different biocatalytic activity and selectivity for radiation induced redox modulation. The single atomic Er-substituted Au clusters show the highest antioxidant activity, and clearance rate to reactive oxygen and nitrogen species (RONS), such as peroxynitrite (ONOO−), nitric oxide (NO) and hydroxyl radicals (OH). Meanwhile, single atomic Cu- or Pt-substituted Au clusters exhibit excellent catalase-like (CAT-like) activity. Moreover, the single atomic Pt-substituted Au clusters also show the best ability to oxidate H2O molecules to OH−. Biological experiments show that Er-substituted Au clusters have good radioreduction ability, which can increase the survival rate of irradiated mice from 40% to 90%. On the contrary, Au clusters substituted by Cu or Pt have the effect of promoting radioxidation, reducing the survival rate of mice to 30% and 0%. These results suggest that antioxidant capacity, RONS scavenging ability and reducibility are closely related to radioreduction, while CAT-like activity and oxidativeness promote radioxidation.

Radiobiology of Select Radionuclides in Hanford Site Tank Waste.

There are several important radionuclides involved in the "clean-up" or environmental isolation of nuclear waste contained in US Department of Energy Hanford Site underground waste tanks that drive many of the decisions associated with this activity. To make proper human health risk analyses and ensure that the most appropriate decisions are made, it is important to understand the radiation biology and the human health risk associated with these radionuclides. This manuscript provides some basic radiological science, in particular radiation biology, for some of these radionuclides, i.e., 3 H, 90 Sr, 137 Cs, 99 Tc, 129 I, and the alpha emitters 239, 240 Pu, 233,234,235,238 U, and 241 Am. These radionuclides were selected based on their designation as "constituents of potential concern," historical significance, or potential impact on human health risk. In addition to the radiobiology of these select radionuclides, this manuscript provides brief discussions of the estimated cost of planned management of Hanford tank waste and a comparison with releases into the Techa River from activities associated with the Mayak Production Association. A set of summary conclusions of the potential human health risks associated with these radionuclides is given.