Effects Of Low-dose Radiation Research Articles

Effect of low-dose irradiation on the properties of GO and GO membrane

Reduced graphene oxide (rGO) is supposed to have better stability and adsorption properties than graphene oxide (GO). Here, GO was controllable reduced by γ-ray irradiation at low doses of 0–10 kGy. Both physicochemical characteristics and filtration performance of GO/rGO membranes were investigated. The XPS, FTIR and UV spectra data showed that both the types and contents of the oxygen-containing functional groups changed after irradiation, but were not linearly correlated with the dose. The irradiation doses of 2 and 10 kGy were two important points, at which the largest C/O values were found. Although the types of the oxygen-containing functional groups were different, the rGO membranes at 2 and 10 kGy both showed the largest flux and the lowest rejection during the long-term filtration. The performance of the rGO membrane is highly influenced by the content rather than the types of oxygen-containing functional groups. The rGO membrane was more stable than the GO membrane at low GO load during the long-term filtration. The rejections of both dye and ions decreased along running time and adsorption was the main mechanism. Different performances were found for the long and short-term filtration. The balance of flux and rejection, as well as the long-term test should be paid more attention during the application of GO/rGO membranes.

Screening of candidate genes related to low-dose ionizing radiation based on transcriptome-proteome correlation research techniques

Objective: To identify the related genes of low-dose ionizing radiation on basis of association analysis of transcriptome and proteome data, and provide new clues for the molecular mechanism of low-dose radiation (LDR) effect. Methods: In March 2018, healthy human peripheral blood was used as materials for transcriptome sequencing and proteome analysis after exposure to radiation at 150 mGy (treatment group) and no radiation (control group) , with three samples in each group. The total RNA and protein were extracted and then correlation analysis of transcriptomic and proteomic were performed to determine LDR effect-related genes, and after that, the biological process and molecular function were analyzed. Results: A total of 486 genes and 266 proteins were identified differentially expressed between treatment group and control group, respectively. Twelve genes and related proteins were found correlated (P<0.05) . The overall correlation between quantitative protein and gene was low (rs=0.0034) , the differential gene with the same change trend was positively correlated with protein expression (rs=0.6786) , and the differential gene with the opposite change trend was negatively correlated with protein expression (rs=-0.1000) . Seven differentially expressed genes (DEGs) showed the same trend as proteins, among which FBXO7 and SNCA were up-regulated as well as ORM1, ORM2, HIST1H4J, HBZ and LYZ were down-regulated. Five DEGs showed the opposite trend as proteins, including SLC4A1, BCAM, C4B_2, KEL, TGM2 up-regulated in transcription level and down-regulated in protein expression level. These DEGs were involved in various biological processes such as immune system regulation, signal transduction, enzyme activity regulation, transmembrane transport, defense, transcription and DNA repair, which indicated their important roles in response to LDR in human peripheral blood. Conclusion: Twelve candidate genes related to LDR effect and their corresponding expressed proteins are screened by the correlation research of transcriptome and proteome data, which provides new clues for the further study of the mechanism of LDR effect.

Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts.

Until recently, radiation effects have been considered to be mainly due to nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures to ionizing radiation (IR) highly depend on activation and regulation through other molecular components of organelles that determine cell survival and proliferation capacities. As typical epigenetic-regulated organelles and central power stations of cells, mitochondria play an important pivotal role in those responses. They direct cellular metabolism, energy supply and homeostasis as well as radiation-induced signaling, cell death, and immunological responses. This review is focused on how energy, dose and quality of IR affect mitochondria-dependent epigenetic and functional control at the cellular and tissue level. Low-dose radiation effects on mitochondria appear to be associated with epigenetic and non-targeted effects involved in genomic instability and adaptive responses, whereas high-dose radiation effects (>1 Gy) concern therapeutic effects of radiation and long-term outcomes involving mitochondria-mediated innate and adaptive immune responses. Both effects depend on radiation quality. For example, the increased efficacy of high linear energy transfer particle radiotherapy, e.g., C-ion radiotherapy, relies on the reduction of anastasis, enhanced mitochondria-mediated apoptosis and immunogenic (antitumor) responses.

Dimethylaminomicheliolide Sensitizes Cancer Cells to Radiotherapy for Synergistic Combination with Immune Checkpoint Blockade.

Radiotherapy (RT) has demonstrated synergy with immune checkpoint blockade (ICB) in preclinical models. However, its potential as an immunoadjuvant is limited by low immunogenicity at low radiation doses and immunosuppression at high radiation doses. It is hypothesized that radiosensitizers can enhance both the anticancer and immunogenic effects of low-dose radiation. Herein the authors report the antitumor immunity of combined RT and immunotherapy with dimethylaminomicheliolide (DMAMCL), a prodrug of the anti-inflammatory sesquiterpene lactone micheliolide (MCL). DMAMCL sensitized cancer cells to a single fraction of RT in vitro by inducing apoptosis and DNA double-strand breaks. DMAMCL with 5 fractions of 2 Gy focal X-ray irradiation led to significant anticancer efficacy in subcutaneous and spontaneous models of murine cancer. DMAMCL-sensitized RT upregulated programmed death-ligand 1 (PD-L1) expression in the tumors. Combination of DMAMCL-sensitized RT with anti-PD-L1 ICB significantly enhanced antitumor efficacy by increasing tumor-infiltrating CD4+ and CD8+ T cells and establishing immune memory.

Effect of Low-Dose Gamma Radiation and Lipoic Acid on High- Radiation-Dose Induced Rat Brain Injuries

AimThis work aims to investigate the possible radio-adaptive mechanisms induced by low-dose (LD) whole-body γ-irradiation alone or combined with alpha-lipoic acid (ALA) administration in modulating high-dose (HD) head irradiation–induced brain injury in rats.Materials and MethodsRats were irradiated with LD (.25 Gy) 24 hours prior HD (20 Gy), and subjected to ALA (100 mg/kg/day) 5 minutes after HD and continued for 10 days. At the end of the experiment, animals were sacrificed and brain samples were dissected for biochemical and histopathological examinations.ResultsHD irradiation-induced brain injury as manifested by elevation of oxidative stress, DNA damage, apoptotic, and inflammatory markers in brain tissue. Histological examination of brain sections showed marked alterations. However, LD alone or combined with ALA ameliorated the changes induced by HD.ConclusionUnder the present experimental conditions, LD whole-body irradiation exhibited neuroprotective activity against detrimental effects of a subsequent HD head irradiation. This effect might be due to the adaptive response induced by LD that activated the anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms in the affected animals making them able to cope with the subsequent high-dose exposure. However, the combined LD exposure and ALA supplementation produced a further modulating effect in the HD-irradiated rats.

The Adaptive Responses in Non-Small Cell Lung Cancer A549 Cell Lines Induced by Low-Dose Ionizing Radiation and the Variations of miRNA Expression.

ObjectiveTo study the effects of adaptive response in A549 cells induced by low-dose radiation and the miRNAs expression.MethodsA549 cells were irradiated with 50 mGy and 200 mGy initial doses, respectively, and then irradiated with a challenge dose 20 Gy at 6 hours interval. The biological effects and miRNA expression were detected.ResultsThe apoptosis rates of 50 mGy-20 Gy and 200 mGy-20 Gy groups were significantly lower than that of only 20 Gy irradiation group (P < .05). The percentage of G2/M phase cells of 50 mGy-20 Gy and 200 mGy-20 Gy groups was significantly decreased relative to the 20 Gy group (P < .05). One miRNA (mir-3662) was upregulated and 15 miRNAs (mir-185, mir-1908, mir-307, mir-182, mir-92a, mir-582, mi-r501, mir138-5p, mir-1260, mir-484, mir-378d, mir-193b, mir-127-3p, mir-1303, and mir-654-5p) were downregulated both in 50 mGy-20 Gy and 200 mGy-20 Gy groups than that of the 20 Gy group. Go and KEGG enrichment analysis showed that the target genes were significantly enriched in cell communication regulation, metabolic process, enzyme binding, and catalytic activity signaling pathways.ConclusionLow-dose X-ray of 50 mGy and 200 mGy radiation can induce adaptive apoptosis response prior to 20 Gy in A549 cells. Sixteen differently expressed miRNAs may play important roles in the adaptive effect of low-dose radiation.

ALARA in practice—4 decades of radiological protection at Goesgen NPP

This paper provides an overview of results achieved through a whole set of ALARA investigations at the Goesgen Nuclear Power Plant. Doses to workers, the public and the environment have significantly dropped in recent years. Even the doses to the most exposed workers at the plant are not bigger than doses from natural background radiation. Recent reviews of epidemiological data call attention to the importance of recognising that the risk of cancer at low doses is small and might contribute only a very small, non-detectable fraction to an individual’s overall risk. Based on the global cultural change on how society is facing any kind of risk, the initial ALARA philosophy is moving more and more to a continuing expectation that optimisation is equivalent to reduction. This philosophy change is even more pronounced in the light of the ongoing discussions about the effects of low dose radiation. Multiple conservatisms in dose models and dose calculations will lead to an imbalance between radiation risks and benefits. Overweighting radiation risks from low doses causes anxiety among the public and unnecessary economic burden to nuclear facilities. In light of pressing global issues (i.e. climate change), a discussion about the meaning of the ‘R’ in ALARA is recommended.

Low-dose radiation-induced demethylation of 3β-HSD participated in the regulation of testosterone content.

The effects of low-dose radiation (LDR, ≤0.1Gy) on living organisms have been the hot areas of radiation biology but do not reach a definitive conclusion yet. So far, few studies have adequately accounted for the male reproductive system responses to LDR, particularly the regulation of testosterone content. Hence, this study was designed to evaluate the effects of LDR on Leydig cells and testicular tissue, especially the ability to synthesize testosterone. We found that less than 0.2-Gy 60 Co gamma rays did not cause significant changes in the hemogram index and the body weight; also, pathological examination did not find obvious structural alterations in testis, epididymis, and other radiation-sensitive organs. Consistently, the results from in vitro showed that only more than 0.5-Gy gamma rays could induce remarkable DNA damage, cycle arrest, and apoptosis. Notably, LDR disturbed the contents of testosterone in mice serums and culture supernatants of TM3 cells and dose dependently increased the expression of 3β-HSD. After cotreatment with trilostane (Tril), the inhibitor of 3β-HSD, increased testosterone could be partially reversed. Besides, DNA damage repair-related enzymes, including DNMT1, DNMT3B, and Sirt1, were increased in irradiated TM3 cells, accompanying by evident demethylation in the gene body of 3β-HSD. In conclusion, our results strongly suggest that LDR could induce obvious perturbation in the synthesis of testosterone without causing organic damage, during which DNA demethylation modification of 3β-HSD might play a crucial role and would be a potential target to prevent LDR-induced male reproductive damage.

Comparative analysis of physical doses and biomarker changes in subjects underwent Computed Tomography, Positron Emission Tomography-Computed Tomography, and interventional procedures

Even though the medical uses of ionizing radiation are well-acknowledged globally as vital tools for the improvement of human health, they also symbolize the major man-made sources of radiation exposure to the population. Estimation of absorbed dose and biological changes after radiation-based imaging might help to better understand the effects of low dose radiation. Because of this, we measured the Entrance Surface Dose (ESD) at different anatomical locations using Lithium tetraborate doped with manganese (Li2B4O7: Mn), recorded Dose Length Product (DLP) and Dose Area Product (DAP), analyzed Chromosomal Aberration (CA), Micronucleus (MN), gamma-H2AX (γ-H2AX), and p53ser15 proteins in the blood lymphocytes of patients (n = 267) underwent Computed Tomography (CT), Positron Emission Tomography-CT (PET/CT), and interventional procedures and healthy volunteers (n = 19). The DLP and effective doses obtained from PET/CT procedures were significantly higher (p < 0.05) when compared to CT. Fluoroscopic time and DAP were significantly higher (p < 0.05) in therapeutic compared to diagnostic interventional procedures. All the anatomical locations registered a significant amount of ESD, the ESD obtained from CT and interventional procedures were significantly (p < 0.05) higher when compared to PET/CT. Fluoroscopic time did not correlate with the ESD (eye, head, thyroid, and shoulder; R2 = 0.03). CA frequency after PET/CT was significantly higher (p < 0.001) when compared to CT and interventional procedures. MN frequency was significantly higher in 24-hs (p < 0.001) post-interventional procedure compared to 2-hs. The mean ± SD of mean fluorescence intensity of γ-H2AX and p53ser15 obtained from all subjects underwent PET/CT and interventional procedures did not show a significant difference (p > 0.05) between pre- and post-procedure. However, the relative fluorescence intensity of γ-H2AX and p53ser15 was >1 in 58.5 % and 65.8 % of subjects respectively. Large inter-individual variation and lack of correlation between physical dose and biomarkers suggest the need for robust dosimetry with a large sample size to understand the health effects of low dose radiation.

Organ Dose Reconstruction Applicable for a Japanese Nuclear Worker Cohort: J-EPISODE.

An evaluation of cancer risk based on organ-absorbed dose is underway for the Japanese Epidemiological Study on Low-Dose Radiation Effects (J-EPISODE), which has analyzed health effects in association with radiation exposure evaluated with the personal dose equivalent Hp(10). Although the concept of effective dose and its operational definition of Hp(10) are widely used for radiological protection purposes, effective dose is not recommended for epidemiological evaluation. Organ-absorbed dose was instead adopted for the IARC 15-Country Collaborative study (15-Country study), the International Nuclear Workers Study (INWORKS), the Mayak worker study, and the Life Span Study (LSS) of atomic bomb survivors. The reconstruction method in J-EPISODE followed in principle the approach adopted in the 15-Country Study. As part of the approach of J-EPISODE, a conversion factor from photon dosimeter reading to air kerma was developed using dosimeter response data, which were measured by the experiment using an anthropomorphic phantom, and it was confirmed that the 15-Country study’s assumption of photon energy and geometry distribution in a work environment applied to Japanese nuclear workers. This article focuses on a method for reconstructing the conversion factor from photon dosimeter reading to organ-absorbed photon dose for a Japanese nuclear worker cohort. The model for estimating the conversion factor was defined under the assumption of a lognormal distribution from three concerned bias factors: (1) a dosimeter reading per air kerma, i.e., dosimeter response; (2) an organ-absorbed dose per air kerma; and (3) a factor relating to the differences in dose concepts and calibration practices between the roentgen dosimeter era and the present. Dosimeter response data were cited from the companion paper. Data on organ-absorbed photon dose per air kerma were estimated using a voxel phantom with the average Japanese adult male height and weight. The bias factor for the recorded dose in the roentgen era was defined, considering the backscatter radiation from the human body. The estimated values of organ-absorbed photon dose per air kerma were almost the same as those in ICRP Publication 116, revealing that the effect of differences in body size was almost negligible. The conversion factors from dosimeter reading to organ-absorbed dose were estimated by period (the roentgen era or from then), nuclear facility type (nuclear power plant or other), dosimeter type, and tissue or organ. The estimated conversion factors ranged from 0.7 to 0.9 (Gy Sv−1). The estimated cumulative organ-absorbed photon dose for the participants of J-EPISODE demonstrated that organ-absorbed dose values were approximately 0.8 times the recorded doses if neglecting dose-unit differences. J-EPISODE reconstructed an organ-absorbed dose conversion factor and will evaluate the risk of cancer mortality and morbidity using the organ-absorbed dose in the future.

Biological effects induced by doses of mammographic screening.

Mammography is the diagnostic imaging practice used in screening to detect early lesions suspected of malignancy. It uses a low energy X-ray beam in which a low dose in the order of 2-3mGy is delivered to patient breast cells. However, it has been speculated that it could lead to significant cell damage, when compared to conventional X-ray. We investigated the biological effects of low doses, with mean glandular doses (MGDs) of 2.5mGy and 2.5+2.5mGy, on mammary cells in vitro. We used the non-tumorigenic cell line (MCF-10A) and two tumor cells lines (MCF-7 and MDA-MB-231). Colony formation, apoptosis, and double-strand DNA breaks (DSBs) were quantified. The selected MGD regimens did not alter the formation of colonies by any of the cell lines. MCF-7 cells exhibited a markedly increase in apoptosis, 24h after the single-dose protocol; MCF-10A cells underwent apoptosis only after 72h, with both irradiation regimens, while MDA-MB-231 cells (highly invasive and metastatic) were not susceptible to apoptosis. The detection of γH2AX histone in the nuclei of irradiated cells showed that the double-dose resulted in increase of DSBs, especially in tumor cell lines. Although the health benefits of early breast screening remain indisputable, our future perspective is to better understand the biological basis for the effects of low dose radiation on breast cells and to investigate if and under what conditions there would be a risky situation in repeated mammography screening, in both asymptomatic and symptomatic women.

Hormetic effects of low-dose gamma rays in soybean seeds and seedlings: A detection technique using optical sensors

The use of radiation technology in agriculture has increased remarkably in recent years. The stimulating effect of low-dose gamma rays, known as hormesis, improves the adaptive response of living organisms to more severe challenges. Different areas of agriculture such as plant physiology, crop breeding and seed biology demand accurate methods for real-time diagnosis of the ionizing radiation effect on biological systems. However, traditional measures are still calculated from slow, laborious and destructive techniques, which depend on human vision. Here, we present two robust optical sensors based on multispectral and fluorescence imaging approaches for rapid and non-destructive detection of the hormetic effects of low-dose gamma radiation in soybean seeds and seedings. Multispectral images were acquired from seeds treated with gamma radiation (0, 12, 16 and 20 Gy), and the reflectance, autofluorescence, texture and color features were extracted from images. Next, a chlorophyll fluorescence-based technique was applied to measure the minimal level of fluorescence (F0), maximum fluorescence (FM), average chlorophyll a fluorescence and quantum yield of photosystem II (FV/FM) in seedlings grown from irradiated and non-irradiated seeds. Using a reflectance technology, the seedlings were also evaluated for anthocyanin, chlorophyll a and normalized difference vegetation index (NDVI). Results showed that multispectral and fluorescence-based techniques provide useful information on the hormetic effects of gamma rays in soybean seeds and seedlings, which are invisible to the naked eye. Our findings provide a better understanding of the link between spectral and fluorescence parameters and the hormetic effect of low-dose gamma rays. From a practical point of view, such optical sensors can provide markers for fast, non-destructive and reliable identification of the best gamma-ray doses to stimulate soybean growth parameters. However, we strongly support in-depth studies of the dose–response relationship in seeds with different initial physiological potential from different soybean genotypes.

Young Chinese people's radiological beliefs significantly associated with their opinions on nuclear power

Previous studies suggest a significant correlation between risk perception and acceptance of nuclear power, but opinions of people with different perceived radiological risk seemed not captured. A national online survey was conducted to learn about the correlation between young Chinese people's beliefs about radiation and their opinions about nuclear power. Correlation between the proximity to a nuclear facility and beliefs about radiation is found. Gender and occupation are not revealed as statistically influential. In addition, the analyses suggest that respondents' perceptions of radiological risk are significantly associated with perception of and support for nuclear power. Even though most respondents supported inland nuclear power plants, fear of radiation is likely to result in a more serious NIMBY syndrome. Most respondents overstated the effect of low-dose radiation, worried about a negative impact of radioactive materials released from a nuclear power plant, and wanted to know more about radiation protection and emergency procedures. It implies that many nuclear issues were driven by fear of radiation, and perception of radiological risk appears a critical factor to mitigate worries and implement radiation protection and emergency procedures.

COVID-19-Associated Pneumonia: Radiobiological Insights.

The evolution of SARS-CoV-2 pneumonia to acute respiratory distress syndrome is linked to a virus-induced “cytokine storm”, associated with systemic inflammation, coagulopathies, endothelial damage, thrombo-inflammation, immune system deregulation and disruption of angiotensin converting enzyme signaling pathways. To date, the most promising therapeutic approaches in COVID-19 pandemic are linked to the development of vaccines. However, the fight against COVID-19 pandemic in the short and mid-term cannot only rely on vaccines strategies, in particular given the growing proportion of more contagious and more lethal variants among exposed population (the English, South African and Brazilian variants). As long as collective immunity is still not acquired, some patients will have severe forms of the disease. Therapeutic perspectives also rely on the implementation of strategies for the prevention of secondary complications resulting from vascular endothelial damage and from immune system deregulation, which contributes to acute respiratory distress and potentially to long term irreversible tissue damage. While the anti-inflammatory effects of low dose irradiation have been exploited for a long time in the clinics, few recent physiopathological and experimental data suggested the possibility to modulate the inflammatory storm related to COVID-19 pulmonary infection by exposing patients to ionizing radiation at very low doses. Despite level of evidence is only preliminary, these preclinical findings open therapeutic perspectives and are discussed in this article.

DNA Damage Detection after Chronic Exposure and Radio-adaptive Response of Naturally Occurring Radioactive Materials (NORM)

The objective of this study was to understand the effect of chronic low-dose radiation that induces in vivo radio-adaptive response. The animals were exposed chronically to natural radioactive materials (NORM) for one and two months which correspond to 10 &20 mSv which are comparable to the reality of areas with high background natural radiation (HBNR). Radioactivity assessment of samples was done using a high purity germanium -ray spectrometer. We conduct the study to understand the radio-adaptive response by exposure the experimental animals to challenge dose 2 Gy after continuous exposure to 10 & 20 mSv. Comet assay was performed in addition to some of antioxidant enzymes concentrations (superoxide dismutase (SOD), catalyze enzyme (CAT), reduced and oxidized glutathione (GSH). Chronic exposure to 10 and 20 mSv showed DNA damage as a high elevation in comet assay, parameters. Also the results of the present work showed a low production of antioxidant enzymes CAT, SOD & GSH in both chronic exposure (10 & 20 mSv and challange dose 2 Gy). The exposure to 20 mSv before 2Gy gamma rays resulted in an enhancement of antioxidant enzymes accompanied with decreasing in free radical which is represents as an adaptive response. . It can be said that for low radiation doses, which are less than 100 mSv, their effects differ from high doses, so that it can be said that the body has an adaptive response and the application of the linear non-threshold model must be reviewed for these doses.

АНАЛИЗ ЭФФЕКТОВ НИЗКИХ ДОЗ РАДИАЦИИ НА МЕЗЕНХИМАЛЬНЫЕ СТВОЛОВЫЕ КЛЕТКИ ЧЕЛОВЕКА

Purpose: The aim of the study was to study the effect of low X-ray doses on human mesenchymal stem cells (MSCs) in long-term cultivation in vitro.&#x0D; Material and methods: MSCs of the mucosal gum tissue of human were used. Cells were irradiated using an RUST-M1 X-ray unit (Russia) at doses of 50, 80, 100, 250 and 1000 mGy (dose rate40 mGy/min) and then cultivated according to standard methods. Immunological characteristics and viability of MSCs were evaluated on a FACSCanto II flow cytometer (Becton Dickinson CA, USA) for early and late passengers. Proliferative activity (PA) was evaluated using an xCelligence real-time cell analyzer (ACEA Biosciencs, Inc.).&#x0D; Results: It was shown that the proliferative activity (PA) of MSCs of the mucosal gum tissue which were irradiated at dose 50 mGy is comparable with the control group in long-term cultivation while doses of 100 and 250 mGy showed a decrease of PA. Also non-irradiated MSCs showed a significant decrease of the PA during cultivation in a conditioned medium from cells that received dose of 1000 mGy and an increase of PA during cultivation in a conditioned medium of cells that received doses of 50, 100 and 250 mGy. The cells were previously irradiated at dose 250 mGy showed adaptive response during cultivation in conditioned medium from cells that received dose of 1000 mGy.&#x0D; Сonclusion: The assessment of the effects of low radiation doses was focused on the bystander effect in the presented study. It was noted after adding conditioned media from irradiated cells to previously irradiated and non-irradiated MSCs. The bystander effects for low and high doses are different and their biological meaning requires further study. The phenomenon of adaptive response was shown after addition conditioned media from cells irradiated at dose 1000 mGy to pre-irradiated MSCs received a dose of 250 mGy. The obtained result leads to the conclusion that the effects of low doses can be positive. Thus, the results of study mainly correspond to the threshold nonlinear concept, according to which the effect is not proportional to the received radiation dose.

Low dose gamma irradiation attenuates cyclophosphamide-induced cardiotoxicity in rats: role of NF-κB signaling pathway

Purpose Cyclophosphamide (Cyp) is one of the most commonly used, wide spectrum chemotherapeutic agents. Cyp has multi-organ toxicities that are dose limiting, thus it’s mostly used in chemotherapeutic combinations. Radiation is well known as a hazardous sort of energy, recent studies are interested in studying the beneficial therapeutic effects of low-dose gamma radiation. This study examined the protective effect of two different doses/dose-rates of irradiation either alone or combined with telmisartan against Cyp-induced cardiotoxicity. Materials and methods Rats were divided into seven groups; (1): Control, (2): Cyp, (3–4): 0.05 Gy low dose rate (LDR) irradiation, 0.25 Gy high dose rate (HDR) irradiation, respectively, prior to Cyp dose, (5–7): telmisartan either alone or with 0.05 Gy LDR-irradiation or 0.25 Gy HDR-irradiation, respectively, prior to Cyp dose. The current investigation studied the effect of Cyp alone or combined with different treatment regimens on serum cTn-I and LDH, nuclear factor-κB (NF-κB) pathway (p65/IκB/IKK-α/IKK-ß) in the myocardium. Pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were assessed in addition to histopathological examination of the heart. Results Low-dose irradiation attenuated cardiac enzymes, pro-inflammatory cytokines, NF-κB content, and histology, in both low and HDRs. Furthermore, the combination of low-dose irradiation with telmisartan (an angiotensin-II receptor type-1 blocker and a known cardio-protective drug) offered the best histological results. Conclusions Low-dose irradiation-induced amelioration is partially but not completely through canonical activation of NF-κB, and may have another atypical pathway. While telmisartan probably ameliorates NF-κB totally through canonical pathway.

SOLLID - a single centre study to develop methods to investigate the effects of low radiation doses within nuclear medicine, to enable multicentre epidemiological investigations.

There is continuing debate concerning the risks of secondary malignancies from low levels of radiation exposure. The current model used for radiation protection is predicated on the assumption that even very low levels of exposure may entail risk. This has profound implications for medical procedures involving ionising radiation as radiation doses must be carefully monitored, and for diagnostic procedures are minimised as far as possible. This incurs considerable expense. The SOLLID study (ClinicalTrials.gov Identifier: NCT03580161) aims to develop the methodology to enable a large-scale epidemiological investigation of the effect of radiopharmaceutical administrations to patients undergoing diagnostic nuclear medicine procedures. Patients will undergo a series of scans in addition to that acquired as standard of care to enable the radiation doses delivered to healthy organs to be accurately calculated. Detailed analysis will be performed to determine the uncertainty in the radiation dose calculations as a function of the number and type of scans acquired. It is intended that this will inform a subsequent long-term multicentre epidemiological study that would address the question definitively. Secondary aims of the study are to evaluate the range of absorbed doses that are delivered from diagnostic nuclear medicine procedures and to use current risk models to ascertain the relative risks from these administrations.

Low Radiation Environment Switches the Overgrowth-Induced Cell Apoptosis Toward Autophagy

Low radiation doses can affect and modulate cell responses to various stress stimuli, resulting in perturbations leading to resistance or sensitivity to damage. To explore possible mechanisms taking place at an environmental radiation exposure, we set-up twin biological models, one growing in a low radiation environment (LRE) laboratory at the Gran Sasso National Laboratory, and one growing in a reference radiation environment (RRE) laboratory at the Italian National Health Institute (Istituto Superiore di Sanità, ISS). Studies were performed on pKZ1 A11 mouse hybridoma cells, which are derived from the pKZ1 transgenic mouse model used to study the effects of low dose radiation, and focused on the analysis of cellular/molecular end-points, such as proliferation and expression of key proteins involved in stress response, apoptosis, and autophagy. Cells cultured up to 4 weeks in LRE showed no significant differences in proliferation rate compared to cells cultured in RRE. However, caspase-3 activation and PARP1 cleavage were observed in cells entering to an overgrowth state in RRE, indicating a triggering of apoptosis due to growth-stress conditions. Notably, in LRE conditions, cells responded to growth stress by switching toward autophagy. Interestingly, autophagic signaling induced by overgrowth in LRE correlated with activation of p53. Finally, the gamma component of environmental radiation did not significantly influence these biological responses since cells grown in LRE either in incubators with or without an iron shield did not modify their responses. Overall, in vitro data presented here suggest the hypothesis that environmental radiation contributes to the development and maintenance of balance and defense response in organisms.

Long-term exposure to low doses of ionizing radiation and COVID-19 pandemic: oncohematological aspects.

For more than 35years after Chornobyl catastrophe, about 5million people in Ukraine, Republic of Belarus and Russian Federation inhabit the territories that are residually contaminated with long-lived radionuclides such as 137Cs, 90Sr. The previous studies of the Reference Laboratory operating at RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology allowed specifying the effects of the protracted low dose irradiation on the state of the hematopoietic and lymphoid tissues resulting in the increased proportion of the B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma and acute myeloid leukemia among the patients referred from the contaminated areas of Ukraine. Since the beginning of 2020, these effects of radiation were superimposed by the factors associated with COVID-19pandemic. SARS-CoV-2infection is associated with the significant impact on hematopoiesis and immune system. Particular attention should be given to the role of such combined burden in the development of the immunodeficiency-associated lymphoid neoplasms. The extensive studies of the combined effects of low dose irradiation and COVID-19within the large affected populations could be made a priority in future endeavors of epidemiologists and oncohematologists.