Effects Of Low-dose Radiation Research Articles

Nrf2 and NF-қB interplay in tamoxifen-induced hepatic toxicity: A promising therapeutic approach of sildenafil and low-dose γ radiation.

Tamoxifen-induced hepatotoxicity is an inevitable side effect during breast cancer treatment. Low-dose gamma irradiation (IRR) shows many beneficial effects by stimulating various biological processes. This study evaluates the possible effect of sildenafil and low-dose gamma radiation on liver damages as new treatment strategies. Group I (control), group II: (tamoxifen), group III: (tamoxifen + Sildenafil), group IV: (tamoxifen+ irradiation) and group V: (tamoxifen +Sildenafil + irradiation). Rats were sacrificed after 5h from tamoxifen injection. Results showed that tamoxifen caused elevation in serum AST, ALT and ALP as well hepatic ROS, iNOS, MDA, Keap-1 and NF-Kb, in addition to diminution in hepatic Nrf2 and HO-1. Exposure to low-dose gamma radiation and sildenafil amended the alterations in the measured parameters in serum and tissue. Moreover, all results were confirmed by histopathological examination. In conclusion, sildenafil and low-dose gamma radiation can mitigate the toxicity induced by tamoxifen in liver tissues. Hence, this treatment could be further evaluated as a new approach for alleviating various liver disorders.

Optimal timing of a γH2AX analysis to predict cellular lethal damage in cultured tumor cell lines after exposure to diagnostic and therapeutic radiation doses.

Phosphorylated H2AX (γH2AX) is a sensitive biomarker of DNA double-strand breaks (DSBs). To assess the adverse effects of low-dose radiation (<50mGy), γH2AX levels have typically been measured in human lymphocytes within 30min of computed tomography (CT) examinations. However, in the presence of DSB repair, it remains unclear whether γH2AX levels within 30min of irradiation completely reflect biological effects. Therefore, we investigated the optimal timing of a γH2AX analysis to predict the cell-surviving fraction (SF). Three tumor cell lines were irradiated at different X-ray doses (10-4000mGy), and the relationships between SF and relative γH2AX levels were investigated 15min and 2, 6, 12 and 24h after irradiation. Data were analyzed for high-dose (0-4000mGy) and low-dose (0-500mGy) ranges. Correlations were observed between SF and the relative number of γH2AX foci/nucleus at 12h only (R2 = 0.68, P = 0.001 after high doses; R2 = 0.37, P = 0.016 after low doses). The relative intensity of γH2AX correlated with SF 15min to 12h after high doses and 2 to 12h after low doses, with the maximum R2 values being observed 2h after high doses (R2 = 0.89, P < 0.001) and 12h after low doses (R2 = 0.65, P < 0.001). Collectively, cellular lethal damage in tumor cells was more accurately estimated with residual DSBs 12h after low-dose (10-500mGy) irradiation. These results may contribute to determination of the optimal timing of biodosimetric analyses using γH2AX in future studies.

Suicide and other causes of death among Chernobyl cleanup workers from Estonia, 1986 − 2020: an update

Mortality was studied in a cohort of 4831 men from Estonia who participated in the environmental cleanup of the radioactively contaminated areas around Chernobyl in 1986–1991. Their mortality in 1986–2020 was compared with the mortality in the Estonian male population. A total of 1503 deaths were registered among the 4812 traced men. The all-cause standardized mortality ratio (SMR) was 1.04 (95% CI 0.99–1.09). All-cancer mortality was elevated (SMR 1.16, 95% CI 1.03–1.28). Radiation-related cancers were in excess (SMR 1.20, 95% CI 1.03–1.36); however, the excesses could be attributed to tobacco and alcohol consumption. For smoking-related cancers, the SMR was 1.20 (95% CI 1.06–1.35) and for alcohol-related cancers the SMR was 1.56 (95% CI 1.26–1.86). Adjusted relative risks (ARR) of all-cause mortality were increased among workers who stayed in the Chernobyl area ≥ 92 days (ARR 1.20, 95% CI 1.08–1.34), were of non-Estonian ethnicity (ARR 1.33, 95% CI 1.19–1.47) or had lower (basic or less) education (ARR 1.63, 95% CI 1.45–1.83). Suicide mortality was increased (SMR 1.31, 95% CI 1.05–1.56), most notably among men with lower education (ARR 2.24, 95% CI 1.42–3.53). Our findings provide additional evidence that unhealthy behaviors such as alcohol and smoking play an important role in shaping cancer mortality patterns among Estonian Chernobyl cleanup workers. The excess number of suicides suggests long-term psychiatric and substance use problems tied to Chernobyl-related stressors, i.e., the psychosocial impact was greater than any direct carcinogenic effect of low-dose radiation.

A short Review of the ALARA Principle in Radiation Protection

Any activity involving radiation should be planned and conducted in such a way that the exposures to individuals are optimally low, taking into consideration the economic and cost aspects. This principle of optimization is called ALARA. ALARA stands for “As Low as Reasonably Achievable”. The ALARA principle states that the radiation exposures should be limited to a minimum level since the Ionizing radiation may produce biological effects in the exposed person. Background of ALARA Concept: The introduction of ALARA was a great philosophical change, as instead of working up to the permissible exposure limits, the idea was to keep exposures to levels as far below the limits as could reasonably be done, considering economic and technical factors. The linear-no-threshold (LNT) model, labeled is the basis of the ALARA protocol; if even small doses lead to slight increases in the risk of cancer than doses should be kept as low as possible. The concept of ALARA was first introduced in 1954 in the National Council on Radiation Protection &amp; Measurements (NCRP) Report, and later in International Commission on Radiological Protection (ICRP) Publication 1 where it was initially called ALAP, the acronym for As Low As Practicable (ICRP 1959b). As per Atomic Energy Regulatory Board (AERB), Govt of India, all radiation work should be carried out in a preplanned and controlled manner so that the exposure to the workers and persons in and near sites of radiation use is kept as low as reasonably achievable (ALARA) and does not exceed the recommended limits. Suitable control measures shall be employed to minimize radiation exposure so that maximum benefits are derived with minimum radiological risk. Discussion: The ALARA principle appears simple but is often misinterpreted and inappropriately applied in radiation protection. It is often interpreted as “as low as possible” without taking into consideration the balancing factors. Considering radiation shielding requirements as an example excessive unnecessary shielding with materials such as lead, steel, or concrete is a waste of global resources. This in turn can cause other damages such as chemical harm and pollution to the environment, which have proven damages to human health. It is more meaningful to make use of the wasted resources for service improvements, such as reducing the charges to patients, investing in better medical technologies, and training of staff. Conclusion: The aims of radiation protection are (i) to avoid the occurrence of deterministic effects and (ii) to limit the risk of stochastic effects. ALARA protocol has successfully limited the exposure of radiation workers to impressively low levels of dose around 1 mSv. Since significant costs are incurred to comply with ALARA and the validity of the LNT model is unclear below doses of 100 mSv, more research on the health effects of low radiation doses is necessary before alternatives to ALARA can become viable.

Low-Dose Radiation Reduces Doxorubicin-Induced Myocardial Injury Through Mitochondrial Pathways.

The use of doxorubicin (DOX) as an anthraquinone antineoplastic agent is limited due to its cardiotoxicity. Our previous study suggested that low-dose radiation (LDR) could mitigate the cardiotoxicity induced by DOX via suppressing oxidative stress and cell apoptosis. However, the molecular targets and protective mechanism of LDR are not understood. In the present study, we sought to investigate the mechanisms underlying LDR's cardioprotection. Balb/c mice were randomly divided into four groups: Control group (no treatment), DOX group, LDR group (75mGy), and LDR-72h-DOX group (LDR pretreatment followed by intraperitoneal injection of DOX). Electron microscopy, PCR, and Western blot analyses indicated that LDR pretreatment mitigated changes in mitochondrial morphology caused by DOX, upregulated activity of mitochondrial complexes, and restored ATP levels in cardiomyocytes that were decreased by DOX. Whole genome microarray and PCR analyses showed that mitochondrial-related genes were altered by LDR pretreatment. Thus, our study showed that LDR can protect cardiomyocytes against DOX through improving mitochondrial function and increasing ATP production. This research could inform DOX chemotherapy strategies and provide new insight into the molecule mechanisms underlying the cardioprotective effects of LDR.

Long-term LDR exposure may induce cognitive impairments: A possible association through targeting gut microbiota-gut-brain axis

Environmental and occupational low-dose radiation (LDR) exposure may be harmful for health but the previous reports regarding effect of LDR on cognition are contradictory. Here we investigated the effect of long-term LDR exposure on cognition. In this study, male Balb/c mice’ cognitive functions were tested at 15 weeks after being exposed to 0.5 Gy LDR in 10 fractions at each dose of 0.05 Gy. The results demonstrated that long-term LDR exposure increases escape latency and the time spent in finding exits in mice compared with non LDR exposure. Meanwhile, the inflammation-related proteins including NFκB and p38 also increased. Lipopolysaccharide (LPS) increased and short-chain fatty acid (SCFA) levels decreased following long term LDR exposure. Treatment with microbiota-derived LPS and SCFAs reversed these effects in mice. Furthermore, the gut barrier integrity was damaged in a time-dependent manner with the decreased expression of intestinal epithelial-related biomarkers such as ZO-1 and occludin. Mechanistically, long after exposure to LDR, increased LPS levels may cause cognitive impairment through the regulation of Akt/mTOR signaling in the mouse hippocampus. These findings provide new insight into the clinical applications of LDR and suggest that the gut microbiota–plasma LPS and SCFAs–brain axis may underlie long-term LDR-induced cognition effects.

Effects of low-dose radiation on human blood components after in vitro exposure to gamma radiation from 137Cs radioactivity

This current study was designed to determine the effects of in vitro exposure to radioactive cesium-137 on human blood components. Whole blood samples were given a radiation dose of 0.02, 0.05, 0.1, 0.2, and 0.3 mGy of gamma radiation using a 137Cs radioactive standard source. The whole blood samples that were exposed to 0 mGy served as sham-controls. The spectrofluoroscopic technique was used to determine the autofluorescence spectrum of protein in plasma or red blood cells by using excitation wavelength and range of emission wavelengths at 280 nm and 300–550 nm, respectively. The hemolysis of red blood cells was evaluated by determination of the release of hemoglobin from the red blood cells to the supernatant. Complete blood counts were also determined in whole blood. The results showed that there was no change in the ratio of fluorescence emission intensity at 340 nm of wavelength of protein extract from irradiated whole blood or red blood cells compared to the corresponding non-irradiated control. The hemolysis value did not change in irradiated whole blood when compared to the corresponding non-irradiated group. In addition, complete blood count values in irradiated groups did not differ from non-irradiated group. These current results suggested that there were no harmful effects of the low-dose gamma radiation from radioactive 137Cs on blood components when human whole blood was exposed to gamma radiation in an in vitro condition.

Biological Effects of Low Dose and Low Dose Rate Radiation

Biological Effects of Low Dose and Low Dose Rate Radiation

LDR-adapted liver-derived cytokines have potential to induce atherosclerosis

Purpose Atherosclerosis is a lipid-driven chronic inflammatory disease that causes cardiovascular diseases (CVD). The association between radiation and atherosclerosis has already been demonstrated; however, the effects of low-dose radiation (LDR) exposure on atherosclerosis have not been reported. Our study aims to propose that LDR may cause atherosclerosis phenotypes by the upregulation of plasminogen activator inhibitor-1 (PAI-1) and downregulation of androgen receptor (AR), which are cytokines secreted from the liver. Methods Low-density lipoprotein (LDL) receptor deficient (Ldlr−/−) mice were irradiated at 50 mGy, 100 mGy, and 1000 mGy. LDR irradiated Ldlr−/− mice serum was analyzed by cytokine array and proteomics with silver staining. Oil Red O staining and BODIPY staining were performed to determine lipid accumulation in Human umbilical vein endothelial cells (HUVECs). Foam cell formation and monocyte recruitment were assessed through co-culture system with HUVECs and THP-1 cells. Results After irradiation with LDR (100 mGy) the mice showed atherosclerotic phenotypes and through analysis results, we selected regulated cytokines, PAI-1 and AR, and found that these were changed in the liver. LDR-regulated cytokines have the potential to be transported to endothelial cells and induce lipid accumulation, inflammation of monocytes, increased oxidized low-density lipoprotein (oxLDL) and foam cells formation, that were series of phenotypes lead to plaque formation in endothelial cells and induces atherosclerosis. As a further aspect of this study, testosterone undecanoate (TU) was found to pharmacologically inhibit a series of atherosclerotic phenotypes exhibited by LDR. This study suggests a role for PAI-1 and AR in regulating the development of atherosclerosis after LDR exposure. Targeting PAI-1 and AR could serve as an attractive strategy for the management of atherosclerosis following LDR exposure.

Radiation dose and gene expression analysis of wild boar 10 years after the Fukushima Daiichi Nuclear Plant accident

The Fukushima Daiichi Nuclear Power Plant accident led to contamination with radioactive cesium in an extensive environment in Japan in 2011. We evaluated the concentration of radioactive cesium in the skeletal muscles of 22 wild boars and the expression of IFN-γ, TLR3, and CyclinG1 in the small intestine and compared them with those of wild boar samples collected from Hyogo prefecture. The average 137Cs radioactivity concentration in wild boars in the ex-evacuation zone was 470 Bq/kg. Most of samples still showed radioactivity concentration that exceeded the regulatory limit for foods, but the dose remarkably decreased compared with samples just after the accident. IFN-γ expression was significantly higher in wild boars in the ex-evacuation zone than in samples from Hyogo prefecture. TLR3 expression was also upregulated. CyclinG1 expression also tended to be high. Hence, wild boars might have received some effects of low-dose radiation, and immune cells were activated to some extent. However, pathological examination revealed no inflammatory cell infiltration or pathological damage in the small intestine of wild boars in the ex-evacuation area. Long-term monitoring would be necessary, but we consider that the living body responds appropriately to a stimulus from a contaminated environment.

Biological Effects of Low Dose Radiation (LDR) on Peri-Tumoral and Tumoral Areas with Squamous Cell Skin Cancer

<h3>Purpose/Objective(s)</h3> Low dose radiation (LDR) may have paradoxically beneficial effects via an adaptive response. We aimed to assess the adaptive response of healthy and malignant skin tissue to low doses of radiation and explore the molecular details behind the induced adaptive response. <h3>Materials/Methods</h3> We conducted a prospective, randomized pilot study (N=8) to ascertain the biological effects of integrating 0.1 Gy of LDR into standard radiotherapy sessions (2.0 Gy fractions) over the first two weeks of radiotherapy for patients 18-80 years of age (both sexes) diagnosed with squamous cell carcinoma of skin (lesions of 1 – 10 cm). Radiation treatment was done with a linear accelerator. The patients received definitive radiation for the tumor as determined by the treating physician using 2.0 Gy fractions. In addition, 0.1 Gy of LDR was integrated into the standard radiotherapy course on day 0 and day 6 over the first two weeks of treatment. Radiation delivery to healthy tissue was with a 1.5 cm margin around the tumor using a mask over the tumor. We obtained partial thickness skin biopsy samples of the tumor and peri-tumoral normal tissue before treatment from four patients (for control). An additional four patients (actively treated) were biopsied before and 24 hours after 0.1 Gy of LDR (day 0, 1 and day 6, 7). RNA was obtained from skin biopsies and processed for genetic expression (138K genes). <h3>Results</h3> The change in gene expression in healthy peri-tumoral tissues due to LDR exposure was relatively low (only 325 genes: 170 upregulated, 155 downregulated). The <i>senescence and autophagy in cancer</i> and <i>genotoxicity pathway</i> genes showed the most significant downregulation in peritumoral healthy tissue comparing days 0 and 1. The biological pathways in peritumoral healthy tissue comparing days 6 and 7 showed predominantly downregulation of genes with most pronounced downregulation seen in <i>electron transport chain in mitochondria</i> and genes involved in <i>non-alcoholic fatty liver disease</i>. In contrast to normal peritumoral tissue, the difference in gene expression in tumor tissue due to LDR exposure was significantly more pronounced (5,651 genes: 2,896 upregulated, 2,755 downregulated) The <i>allograft rejection</i> genes and <i>nuclear receptor meta-pathway</i> were the most upregulated in the tumoral tissues comparing days 0 and 1. The nuclear receptor meta-pathway were the most upregulated in the tumoral tissues on days 6 and 7. The <i>Allograft rejection pathway in skin cancer</i> was among those upregulated. <h3>Conclusion</h3> LDR had a modest effect on miRNA expression when applied to healthy peritumoral skin. Downregulated pathways predominate, and DNA repair mechanisms are stimulated by the first dose in healthy tissue. In contrast, a more pronounced effect on gene expression (as measured by miRNA profiles), including upregulation of several key relevant pathways, was induced by LDR to malignant tissue.

Effect of low-dose radiation on thyroid function and the gut microbiota.

BACKGROUNDThe thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition.AIMTo investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice.METHODSPeripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation.RESULTSWe found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair.CONCLUSIONLDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose.

DNA damage induced by radiation exposure from cardiac catheterization – an analysis in patients and operators

Abstract Background The biological effects of low-dose radiation from cardiac imaging or intervention remain largely unknown. This study aimed to evaluate the effects of ionized radiation from cardiac catheterization on genomic DNA integrity and inflammatory cytokines in patients and operators. Methods Peripheral mononuclear cells (MNCs) were isolated from patients (n=52) and operators (n=35) before and after coronary angiography and/or percutaneous coronary intervention. Expression of gammaH2AX, a marker for DNA double-strand breaks, was measured by immunofluorescence. Dicentric chromosomes (DICs), a form of chromosome aberrations, were assayed using a fluorescent in situ hybridization technique. Results In the patient MNCs, the numbers of gammaH2AX foci and DICs increased after cardiac catheterization by 101±75% and 28±99%, respectively (P&amp;lt;0.05 for both). The mRNA expressions of interleukin (IL)-1α, IL-1β, leukemia inhibitory factor (LIF) and caspase-1 were significantly increased by radiation exposure from cardiac catheterization. The increase in IL-1β was significantly correlated with that of gammaH2AX, but not with dose area product. In the operators, neither gammaH2AX foci nor DICs level was changed, but IL-1β mRNA was significantly increased. Protein expression of IkappaBα was significantly decreased in both groups. Conclusions DNA damage was increased in the MNCs of patients, but not of operators, who underwent cardiac catheterization. Inflammatory cytokines were increased both in the patients and operators, presumably through activation of NF-kappaB. Further efforts to reduce radiation exposure from cardiac catheterization are necessary both for patients and operators. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grants-in-Aid for Scientific Research (KAKENHI)

Low Dose and Non-Targeted Radiation Effects in Environmental Protection and Medicine-A New Model Focusing on Electromagnetic Signaling.

The role of signalling in initiating and perpetuating effects triggered by deposition of ionising radiation energy in parts of a system is very clear. Less clear are the very early steps involved in converting energy to chemical and biological effects in non-targeted parts of the system. The paper aims to present a new model, which could aid our understanding of the role of low dose effects in determining ultimate disease outcomes. We propose a key role for electromagnetic signals resulting from physico-chemical processes such as excitation decay, and acoustic waves. These lead to the initiation of damage response pathways such as elevation of reactive oxygen species and membrane associated changes in key ion channels. Critically, these signalling pathways allow coordination of responses across system levels. For example, depending on how these perturbations are transduced, adverse or beneficial outcomes may predominate. We suggest that by appreciating the importance of signalling and communication between multiple levels of organisation, a unified theory could emerge. This would allow the development of models incorporating time, space and system level to position data in appropriate areas of a multidimensional domain. We propose the use of the term “infosome” to capture the nature of radiation-induced communication systems which include physical as well as chemical signals. We have named our model “the variable response model” or “VRM” which allows for multiple outcomes following exposure to low doses or to signals from low dose irradiated cells, tissues or organisms. We suggest that the use of both dose and infosome in radiation protection might open up new conceptual avenues that could allow intrinsic uncertainty to be embraced within a holistic protection framework.

A Risk Comparison of Non-cancer Mortality between Lifestyle, Socioeconomic Status, and Radiation among Japanese Nuclear Workers (J-EPISODE).

Many epidemiological studies have been conducted to investigate the health effects of low-dose radiation. Most of these investigations have focused on cancer, and fewer studies have examined non-cancer topics than cancer subjects. The purpose of this study is to compare the relative risks of non-cancer mortality from low-dose radiation with lifestyle factors (such as smoking habits) and socioeconomic status (such as years of education). The cohort consisted of 43,692 males who responded to a lifestyle questionnaire survey conducted from 2003 to 2004 among nuclear workers in Japan. Missing questionnaire data were imputed by multiple imputation, each variable was categorized, and the relative risks for the reference group were calculated using Poisson regression. The total number of observed person-years was 300,000, and the mean age and dose were 55.2 y and 24.5 mSv (10-y lagged dose), respectively. For many of the causes of death in this analysis, significantly high risks existed for lifestyle differences, such as smoking, alcohol consumption, frequency of medical examination, breakfast intake, sleep, and BMI, but few for socioeconomic status. Radiation showed no significantly high risks. Taken together, the risk of non-cancer mortality from low-dose radiation is likely smaller than that from lifestyle factors.

Protective effect of low-dose radiation on doxorubicin-induced brain injury in mice

BackgroundTo investigate the protective effect of low-dose radiation (LDR) on brain injury in mice induced by doxorubicin (DOX). MethodsSixty female BALB/C mice were randomly divided into the control (CTR) group, low-dose radiation (LDR) group, doxorubicin treatment (DOX) group and low-dose radiation before doxorubicin treatment (COM) group. After 72 h of exposure to 75 mGy, the mice were intraperitoneally injected with 7.5 mg/kg of doxorubicin and sacrificed 5 days later. Neuron-specific enolase (NSE), lactate dehydrogenase (LDH), adenosine triphosphate (ATP), neurotransmitters, inflammatory mediators, apoptosis- and oxidative stress-related mediators as well as mitochondrial dysfunction were examined. ResultsCompared to the DOX group, the concentrations of DA, 5-HT, EPI and GABA in the COM group were significantly decreased, and the number of TUNEL-positive cells was decreased. In addition, the expression of proapoptotic proteins was downregulated in the COM group compared to the DOX group. Low-dose radiation in advance reduced reactive oxygen species and activated the SOD antioxidant defense system as indicated by significantly reduced GSH expression, increased GSSG expression, increased GPx expression and activation of the Nrf2 redox pathway. After low-dose radiation, the expression levels of ATP5f1, NDUFV1 and CYC1 were close to normal, and the mitochondrial respiratory control rate (RCR) and activity of respiratory chain complex enzymes also tended to be normal. Low-dose radiation upregulated the expression levels of IL-2 and IL-4 but downregulated the expression levels of IL-10 and TGF-β. ConclusionLDR has a protective effect on brain injury in mice treated with DOX. The mechanism is related to LDR alleviating mitochondrial dysfunction and oxidative stress, which promotes the production of antioxidant damage proteins, thus exerting an adaptive protective effect on cells.

High-throughput screening strategies for space-based radiation countermeasure discovery

As humanity begins to venture further into space, approaches to better protect astronauts from the hazards found in space need to be developed. One particular hazard of concern is the complex radiation that is ever present in deep space. Currently, it is unlikely enough spacecraft shielding could be launched that would provide adequate protection to astronauts during long-duration missions such as a journey to Mars and back. In an effort to identify other means of protection, prophylactic radioprotective drugs have been proposed as a potential means to reduce the biological damage caused by this radiation. Unfortunately, few radioprotectors have been approved by the FDA for usage and for those that have been developed, they protect normal cells/tissues from acute, high levels of radiation exposure such as that from oncology radiation treatments. To date, essentially no radioprotectors have been developed that specifically counteract the effects of chronic low-dose rate space radiation. This review highlights how high-throughput screening (HTS) methodologies could be implemented to identify such a radioprotective agent. Several potential target, pathway, and phenotypic assays are discussed along with potential challenges towards screening for radioprotectors. Utilizing HTS strategies such as the ones proposed here have the potential to identify new chemical scaffolds that can be developed into efficacious radioprotectors that are specifically designed to protect astronauts during deep space journeys. The overarching goal of this review is to elicit broader interest in applying drug discovery techniques, specifically HTS towards the identification of radiation countermeasures designed to be efficacious towards the biological insults likely to be encountered by astronauts on long duration voyages.

P-473 Low radiation affects follicle count in sheep ovaries

Abstract Study question What is the effect of low dose radiation on follicle count in sheep ovaries? Summary answer Even low dose radiation has a negative impact on the follicle count in sheep ovaries. What is known already Radiotherapy is a corner stone of state-of-the-art cancer treatment, especially in young cancer patients. Survival rates are constantly rising, resulting in long-term survivors with potential child wish. High doses of radiation lead to a permanent damage to the ovaries. Little is known about the damage after low dose radiation to the ovaries including both follicles and stroma. Study design, size, duration Prospective ongoing study, including n = 41 sheeps and 942 ovarian punches (Ø 3mm). So far, n = 12 sheep and n = 120 punches were analysed between April 2020 and January 2022. After finishing the experiments with sheep ovarian tissue, we will continue with a mouse model and human ovarian tissue. Participants/materials, setting, methods 942 cortex punches out of a total of n = 41 sheep were obtained and cryopreserved. After thawing the punches were radiated with a dose of 0.0, 0.5, or 9.0 Gy using a cesium 137 radionuklide source (GSR C1, GammaService Medical GmbH). The punches were fixed in formalin, embedded in paraffin, cut into serial sections of 3-5 µm and stained with Hematoxylin and Eosin for follicle counting as well as Caspase 3 and Ki67. Main results and the role of chance Follicle loss was already observed after low dose radiation (0.5 Gy). Mean follicle count after 0 Gy, 0.5 Gy, and 9 Gy were 7.5, 2.3 and 1.8, respectively. While after 0 Gy, no signs of degeneration were visible, after radiation with 9 Gy follicles showed strong signs of degeneration including disorganization of granulosa cells, pyknosis and stromal irregularities. Limitations, reasons for caution Limitations of our study include the pilot character and therefore small sample size. The presented data only display part of the overall project including also an in-vivo mouse model. Wider implications of the findings As even low dose radiation seems to damage ovarian follicles, further in-vivo studies are needed to confirm these results. Moreover, fertility preservation methods need to be offered consequently to young cancer patients receiving radiotherapy. Trial registration number 25

Understanding the harm of low-dose computed tomography radiation to the body (Review).

Computed tomography (CT) is a modern examination method whose radiation characteristics vary depending on the population groups, the part of the body being examined, and other implementation conditions. The use of CT has become increasingly widespread. However, there is a growing concern regarding the harm caused by CT radiation. The opinions regarding whether low-dose CT can induce cancer differ. It is necessary to consider the research population, radiation characteristics, and different parts of the body being exposed to radiation before the application of radiation to ensure the knowledge used is scientifically sound and reasonable. Therefore, different studies have different opinions on whether low-dose CT induces cancer, and not all physicians are aware of this. The present review article aimed to impart relevant insights and a correct understanding of the hazardous effects of low-dose CT radiation on the human body and help physicians reduce unnecessary CT radiation exposure.

Complex housing partially mitigates low dose radiation-induced changes in brain and behavior in rats

In recent years, much effort has been focused on developing new strategies for the prevention and mitigation of adverse radiation effects on healthy tissues and organs, including the brain. The brain is very sensitive to radiation effects, albeit as it is highly plastic. Hence, deleterious radiation effects may be potentially reversible. Because radiation exposure affects dendritic space, reduces the brain's ability to produce new neurons, and alters behavior, mitigation efforts should focus on restoring these parameters. To that effect, environmental enrichment through complex housing (CH) and exercise may provide a plausible avenue for exploration of protection from brain irradiation. CH is a much broader concept than exercise alone, and constitutes exposure of animals to positive physical and social stimulation that is superior to their routine housing and care conditions. We hypothesized that CHs may lessen harmful neuroanatomical and behavioural effects of low dose radiation exposure. We analyzed and compared cerebral morphology in animals exposed to low dose head, bystander (liver), and scatter irradiation on rats housed in either the environmental enrichment condos or standard housing. Enriched condo conditions ameliorated radiation-induced neuroanatomical changes. Moreover, irradiated animals that were kept in enriched CH condos displayed fewer radiation-induced behavioural deficits than those housed in standard conditions. Animal model-based environmental enrichment strategies, such as CH, are excellent surrogate models for occupational and exercise therapy in humans, and consequently have significant translational possibility. Our study may thus serve as a roadmap for the development of new, easy, safe and cost-effective methods to prevent and mitigate low-dose radiation effects on the brain.