Effects Of Low-dose Radiation Research Articles

DNA Damage Induced by Radiation Exposure from Cardiac Catheterization

Almost 40% of medical radiation exposure is related to cardiac imaging or intervention. However, the biological effects of low-dose radiation from medical imaging 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.Peripheral mononuclear cells (MNCs) were isolated from patients (n = 51) and operators (n = 35) before and after coronary angiography and/or percutaneous coronary intervention. The expression of γH2AX, 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.In the patient MNCs, the numbers of γH2AX foci and DICs increased after cardiac catheterization by 4.5 ± 9.4-fold and 71 ± 122%, respectively (P < 0.05 for both). The mRNA expressions of interleukin (IL)-1α, IL-1β, leukemia inhibitory factor, and caspase-1 were significantly increased by radiation exposure from cardiac catheterization. The increase in IL-1β was significantly correlated with that of γH2AX, but not with the dose area product. In the operators, neither γH2AX foci nor the DIC level was changed, but IL-1β mRNA was significantly increased. The protein expression of IκBα was significantly decreased in both groups.DNA damage was increased in the MNCs of patients, but not of operators, who underwent cardiac catheterization. Inflammatory cytokines were increased in both the patients and operators, presumably through NF-κB activation. Further efforts to reduce radiation exposure from cardiac catheterization are necessary for both patients and operators.

Genome-Wide RNA Sequencing Analysis in Human Dermal Fibroblasts Exposed to Low-Dose Ultraviolet A Radiation.

Ultraviolet A (UVA) radiation can pass through the epidermis and reach the dermal skin layer, contributing to photoaging, DNA damage, and photocarcinogenesis in dermal fibroblasts. High-dose UVA exposure induces erythema, whereas low-dose, long-term UVA exposure causes skin damage and cell senescence. Biomarkers for evaluating damage caused by low-dose UVA in fibroblasts are lacking, making it difficult to develop therapeutic agents for skin aging and aging-associated diseases. We performed RNA-sequencing to investigate gene and pathway alterations in low-dose UVA-irradiated human skin-derived NB1RGB primary fibroblasts. Differentially expressed genes were identified and subjected to Gene Ontology and reactome pathway analysis, which revealed enrichment in genes in the senescence-associated secretory phenotype, apoptosis, respiratory electron transport, and transcriptional regulation by tumor suppressor p53 pathways. Insulin-like growth factor binding protein 7 (IGFBP7) showed the lowest p-value in RNA-sequencing analysis and was associated with the senescence-associated secretory phenotype. Protein–protein interaction analysis revealed that Fos proto-oncogene had a high-confidence network with IGFBP7 as transcription factor of the IGFBP7 gene among SASP hit genes, which were validated using RT-qPCR. Because of their high sensitivity to low-dose UVA radiation, Fos and IGFBP7 show potential as biomarkers for evaluating the effect of low-dose UVA radiation on dermal fibroblasts.

Unlaid Eggs: Ovarian Damage after Low-Dose Radiation.

The total body irradiation of lymphomas and co-irradiation in the treatment of adjacent solid tumors can lead to a reduced ovarian function, premature ovarian insufficiency, and menopause. A small number of studies has assessed the radiation-induced damage of primordial follicles in animal models and humans. Studies are emerging that evaluate radiation-induced damage to the surrounding ovarian tissue including stromal and immune cells. We reviewed basic laboratory work to assess the current state of knowledge and to establish an experimental setting for further studies in animals and humans. The experimental approaches were mostly performed using mouse models. Most studies relied on single doses as high as 1 Gy, which is considered to cause severe damage to the ovary. Changes in the ovarian reserve were related to the primordial follicle count, providing reproducible evidence that radiation with 1 Gy leads to a significant depletion. Radiation with 0.1 Gy mostly did not show an effect on the primordial follicles. Fewer data exist on the effects of radiation on the ovarian microenvironment including theca-interstitial, immune, endothelial, and smooth muscle cells. We concluded that a mouse model would provide the most reliable model to study the effects of low-dose radiation. Furthermore, both immunohistochemistry and fluorescence-activated cell sorting (FACS) analyses were valuable to analyze not only the germ cells but also the ovarian microenvironment.

The mechanism of low-dose radiation-induced upregulation of immune checkpoint molecule expression in lung cancer cells

IntroductionThis study explored the effect of low-dose radiation on the expression of immune checkpoint molecules in lung cancer cells and its mechanism, as well as the antitumour effect of combined low-dose radiation and immune checkpoint inhibitors. MethodsWestern blot analysis was used to assess the expression of the immune checkpoint molecules CD47, PD-L1, FGL-1 and CD155 in lung cancer cells after radiation. Western blotting was also used to explore changes in the JAK2/STAT3 pathway. CD8+ T lymphocyte infiltration in tumour tissues were assessed by immunohistochemistry in a mouse model. The inhibitory effect of low-dose radiation combined with PD-L1 or CD47 inhibitors on tumor growth was evaluated by measuring tumor volume. ResultsIn response to low-dose irradiation, the expression of CD47 and PD-L1 in A549 and LLC cells was increased, the expression of p-JAK2 and p-STAT3 was also increased. AG490-mediated inhibition of the JAK2/STAT3 pathway before irradiation significantly reduced the expression of p-JAK2 and p-STAT3 in lung cancer cells, in the meantime, expression of CD47 and PD-L1 was also reduced. Conventional dose exposure exhibited the same trend. PD-L1 and CD47 protein levels increased after low-dose irradiation in an LLC tumour-bearing mouse model. Low-dose irradiation combined with PD-L1 or CD47 inhibitor treatment reduced levels of PD-L1 or CD47 in tumour tissues, increased the proportion of CD8+ T lymphocytes, and significantly inhibited tumour growth. ConclusionsBoth low-dose and regular-dose irradiation upregulate expression of the immune checkpoint molecules CD47 and PD-L1 in lung cancer cells, and the mechanism may be related to the JAK2/STAT3 pathway. Furthermore, low-dose irradiation combined with PD-L1 or CD47 inhibitors significantly inhibits tumour growth.

Differential Proliferative Responses to Low-Dose Irradiation between Human Submandibular and Parotid Salivary Ductal Cell Lines

Objective: Salivary glands are frequently exposed to X-radiation during dental radiography. The present study aimed to investigate the proliferative and apoptotic effects of low-dose irradiation on human salivary cell lines in vitro. Materials and Methods: Two distinct ductal cell lines, HSG and HSY, were first characterized by expressions of carcinoembryonic antigen (CEA) and lactoferrin (LF), compared to those in human oral keratinocytes (HOKs), and then examined for their doubling times. They were exposed to periapical radiography for 5, 10, or 20 times, and incubated further for 1, 3, or 5 cycles of their cell division. Cell proliferation was examined by a BrdU assay and immunoblot analysis of Ki-67 expression. Cell apoptosis was determined by the presence of human active caspase 3. Results: The mean degrees of CEA and LF expressions were significantly higher in HSG and HSY than in HOKs (p&lt;0.01). The doubling time of HSG was significantly shorter than that of HSY (p=0.009). Upon repeated exposures to dental X-ray, the proliferation of HSG was significantly increased at the first cycle, whereas that of HSY was significantly decreased (p&lt;0.05). At the third cycle, Ki-67 expression was significantly increased in HSG, while it was significantly decreased in HSY (p=0.037). However, the proliferative effect was temporarily presented in both cells. No active caspase 3 was detected upon exposure to any doses or in any cycles. Conclusion: The two ductal cell lines demonstrated adaptive response to low-dose irradiation by either increased or decreased cell proliferation, but no apoptosis was found in both cell lines. Keywords: Bromodeoxyuridine assay; Cell apoptosis; Cell proliferation; Dental X-ray; Salivary ductal cells

Effect of low dose radiation from general X-ray to T-cell lymphocyte expression using an in vitro method

In medical practice, a general X-ray is necessary for diagnosing various ailments. But using low dose X-rays would induce risk on cells of the patient. The purpose of this study was to examine the low dose radiation-induced cell response of CD3+, CD4+ and CD8+ T-cells. In this experiment, T-cell lymphocytes were collected from healthy volunteers, then were irradiated with 0.47, to 2.30 mGy, referring from general X-ray techniques of chest, abdomen, lumbar spine and pelvis. Using a three-colour flow-cytometry method – which measures CD3+ T-cells and ratios of CD4+ to CD8+ T-cells (CD4/CD8 ratio) for 24, 48, 72 and 96 h after irradiation – we found that the cell morphology did not change after exposure to low dose X-rays. CD3+ T-cell levels were increased compared to the control group in a dose-responsive manner over 48–96 h, similar to the CD4/CD8 ratios which were increased at 72–96 h. In conclusion, the effect of low dose X-rays from general X-ray techniques are dose-dependent on T-cell responses in the in vitro system. The knowledge of low dose radiation effects lets us know about the harmful effects of ionising radiation, especially on cells of the immune system and caution us to the unnecessary use of diagnostic radiology.

Abstract TP194: Radiation And Stroke Death Risk In Diffuse Large B-cell Lymphoma Patients, A Population Based Study.

Objective: Radiation (RT) is associated with vascular changes, which carotid studies have linked with stroke risk. Previous studies have reported an increased risk of stroke following RT for squamous cancers of head &amp; neck (HN), or Hodgkin’s lymphomas, though with variations in dose and anatomical radiation targets. Hence the effects of low dose radiation to only the HN remains unclear. We used a national database with long-term follow up to quantify the association of RT and stroke death (SD) in patients with diffuse large B cell lymphoma (DLBCL) of the HN. Materials/Methods: Patients 30 or older with DLBCL, stage I-II of a known primary site besides CNS or mediastinum from 1983-2013 were obtained for analysis from the SEER database. Cause of death coding was filtered for Cerebrovascular Disease. Chi square, T-test, and Kaplan-Meier analysis were performed with log-rank test and Cox accounting for age, sex, RT, and year of diagnosis. Results: 33945 patients met inclusion criteria with a median follow up of 44 months. SD occurred in 410 patients in median time 62 months. RT was given in 3855 of 8312 (46%) HN and 7686 of 25633 (30%) of non-HN patients. The 10 year-SD rate was 2.2 / 2.8 % (p=0.77) for HN receiving/ not receiving RT (noRT), and 1.8 / 2.1 % for non-HN patients (p=0.40). When combining both RT and noRT patients, HN patients did show a trend towards higher SD risk compared with non-HN patients, 2.5 vs 2.0%, (p=0.053), though this did not appear to be driven by RT. On univariate analysis of HN patients, there was no difference in the effects of RT on the SD rate in any subgroup. Multivariate analysis did not identify any increased risk of SD associated with RT, either (HR = 0.87, p=0.63). Conclusions: This study did not identify any increased risk of stroke death from RT in patients with early stage DLBCL of the head &amp; neck, although there was a trend suggesting stroke rates may be higher in patients with disease located in head &amp; neck compared to other sites regardless of whether they received RT. Higher chemotherapy doses for non-RT patients may be a relevant confounding variable. Confirmation with pooled analyses and meta-analysis may be useful.

Reanalysis of cancer mortality using reconstructed organ-absorbed dose: J-EPISODE 1991‒2010

The Japanese Epidemiological Study on Low-Dose Radiation Effects (J-EPISODE) has been conducted since 1990 by the Radiation Effects Association to analyse health effects for nuclear workers. It uses the recorded doses, i.e. dosimeter readings, evaluated in H p(10) for estimation of radiation risk; however, the International Commission on Radiological Protection does not recommend the use of effective doses for epidemiological evaluation and instead recommends the use of organ-absorbed doses for assessing cancer risk. Recently, the J-EPISODE has developed a conversion factor that can convert dosimeter readings to organ-absorbed doses following, in principle, the approach adopted by the International Agency for Research on Cancer 15-Country Collaborative Study. The approach was modified based on recent dosimeter usage practices and the Japanese physique. The aim of this study was to reanalyse the excess relative risk (ERR) of cancer mortality for the J-EPISODE using the previous analysis method but substituting the organ-absorbed dose for the recorded dose to confirm the adaptability and relevance of organ-absorbed doses for the J-EPISODE. The organ-absorbed doses from 1957 to 2010 were reconstructed for the whole cohort. The cancer mortality risk was reanalysed with Poisson regression methods, first by comparing the ERR/Gy for all cancers excluding leukaemia with the risk after excluding lung cancer for the whole cohort of 204 103 participants. In the whole cohort, all cancers excluding leukaemia, lung cancer and non-Hodgkin’s lymphoma had statistically significant positive ERR/Gy estimates; leukaemia excluding chronic lymphocytic leukaemia had negative but not statistically significant estimates. Gallbladder cancer and pancreatic cancer showed statistically significant negative. Then, a subcohort of 71 733 respondents was selected based on lifestyle surveys with data on qualitative smoking status as well as quantitative smoking information on pack-years. Pack-years for current smokers and former smokers and years since the cessation of smoking for former smokers were used for the smoking-adjusted model. The most important feature of the J-EPISODE revealed to date was a decreasing tendency of the ERR/Sv by the smoking adjustment. For almost all causes of death such as lung cancer and stomach cancer, the estimated ERR/Gy decreased by the smoking adjustment, although those for the colon, prostate and kidney and other urinary organs were almost the same after the adjustment. This tendency remained unchanged even when using the organ-absorbed dose, indicating the appropriateness of using organ-absorbed doses for further risk analysis. At the same time, it indicated that confounding by smoking seriously biased the radiation risk estimates in the J-EPISODE and thus should be accounted even if organ dose is used.

Radiation Effects on Late-life Neurocognitive Function in Childhood Atomic Bomb Survivors: A Radiation Effects Research Foundation Adult Health Study.

High-dose radiation in childhood such as is used in radiation therapy causes cognitive decline, but there is insufficient research on the cognitive effects of low- to medium-dose radiation. We aimed to reveal the association between atomic bomb radiation exposure in childhood and late-life neurocognitive function. In 2011 and 2013, we mailed the Neurocognitive Questionnaire (NCQ) to subjects who were 12 years old or younger at the time of the atomic bombing. We converted the four NCQ subscales (metacognition, emotional regulation, motivation/organization, and processing speed) to T scores and defined the highest 10% of the controls (exposure dose < 5 mGy) as impaired. We used a generalized linear mixed model to evaluate the effect of radiation exposure on T scores and percentage impaired. We enrolled 859 participants. At the time of the bombing, the mean (SD) age was 6.7 (3.8) years for the control (N = 390) and 6.1 (3.8) years for the exposed (N = 469). At the time of replying to the questionnaire, the mean age of all the participants was 73.7 (3.8) years of age. After adjusting for cofactors, older age was related to the decline of all neurocognitive subscales. Sex and education level had relevance to some of the subscales. For neurocognitive function, exposure dose was not related except to percentage impaired, motivation/organization. Late-life neurocognitive function in atomic bomb survivors exposed as children was associated with age, but not clearly with radiation dose. More studies are needed to evaluate the effect of low-dose radiation during childhood on long-term neurocognitive function.

Evaluation of risk due to chronic low dose ionizing radiation exposure on the birth prevalence of congenital heart diseases (CHD) among the newborns from high-level natural radiation areas of Kerala coast, India

BackgroundThe human population residing in monazite bearing Kerala coast are exposed to chronic low dose and low dose rate external gamma radiation due to Th232 deposits in its beach sand. The radiation level in this area varies from < 1.0 to 45.0 mGy/year. This area serves as an ideal source for conducting large-scale epidemiological studies for assessing risk of low dose and low dose rate radiation exposure on human population. The areas with a dose level of ≤1.50 mGy/year are considered as normal level natural radiation areas (NLNRAs) and areas with > 1.50 mGy/year, as high level natural radiation areas (HLNRAs). HLNRAs were further stratified into three dose groups of 1.51-3.0 mGy/year, 3.01-6.00 mGy/year and > 6.0 mGy/year. The present study evaluates the effects of chronic low dose radiation (LDR) exposure on the birth prevalence of Congenital Heart Diseases (CHD) among the live newborns monitored in hospital based prospective study from NLNRAs and HLNRAs of Kerala coast, India.MethodologyConsecutive newborns were monitored from two hospital units located in the study area for congenital malformations. Referred CHD cases among the newborns screened were confirmed by conducting investigations such as pulse oximetry, chest X-ray, electrocardiogram and echocardiogram etc.ResultsAmong the newborns screened, 289 CHDs were identified with a frequency of 1.49‰ among 193,634 livebirths, which constituted 6.03% of overall malformations and 16.29% of major malformations. Multiple logistic regression analysis suggested that the risk of CHD among the newborns of mothers from HLNRAs with a dose group of 1.51-3.0 mGy/year was significantly lower as compared to NLNRA (OR = 0.72, 95% CI: 0.57-0.92), whereas it was similar in HLNRA dose groups of 3.01-6.00 mGy/year (OR = 0.55, 95% CI: 0.31-1.00) and ≥ 6.0 mGy/year (OR = 0.96, 95% CI: 0.50-1.85). The frequency of CHDs did not show any radiation dose related increasing trend. However, a significant (P = 0.005) reduction was observed in the birth prevalence of CHDs among the newborns from HLNRA (1.28‰) as compared to NLNRA (1.79‰).ConclusionChronic LDR exposure did not show any increased risk on the birth prevalence of CHDs from high-level natural radiation areas of Kerala coast, India. No linear increasing trend was observed with respect to different background dose groups. The frequency of CHD was observed to be 1.49 per 1000 livebirths, which was similar to the frequency of severe CHD rate reported elsewhere in India and was much less than the reported frequency of 9 per thousand.

Analysis of Red Blood Cells and their Components in Medical Workers with Occupational Exposure to Low-Dose Ionizing Radiation.

Plenty of reports focus on the effects of low-dose radiation (LDR) on peripheral blood lymphocytes in radiation workers. However, studies on red blood cells (RBCs) in radiation workers are rarely reported. Many studies focused on investigate the hemogram of radiation staffs without detecting other components of RBCs. To explore the potential effect of LDR on RBCs, we detected the level of RBC count, hemoglobin, 2,3-disphosphoglycerate (2,3-DPG), and glutathione (GSH), and then analyzed the factors on these indices in 106 medical radiation workers. As a result, RBC count was affected by sex, age, type of work, length of service (only for females), and annual effective dose (only for males). Hemoglobin status was affected by sex, type of work, and annual effective dose (only for males). Sex, age, and type of work had no effects on the concentration of 2,3-DPG and GSH. Length of service affected 2,3-DPG concentration, and annual effective dose affected GSH level. In conclusion, chronic occupational LDR exposure may have an effect on RBC count, hemoglobin status, and the concentration of 2,3-DPG and GSH in radiation workers to some extent. However, it is still unknown how this kind of influence affects the health of radiation workers.

RELEVANT BIOCHEMICAL INDICES OF BLOOD RADIOSENSITIVITY IN GYNECOLOGICAL CANCER PATIENTS.

identification of the relevant biochemical indices of blood radiosensitivity in endometrial cancerpatients under the test irradiation in a wide range of doses. Peripheral blood samples were drawn for assay in the newly diagnosed endometrial cancer patients (study group, n = 42) and healthy donors (control group, n = 27). A set of biochemical values was reviewed to identify and justify the prognostic markers of cell radiosensitivity in the tumor environment featuring gradual development of oxidative stress, namely the intensity of superoxide anionradical (О2) generation, pro/antioxidant ratio (PAR), and malondialdehyde (MDA) content. Predictive values were selected through the construction and analysis of «doseresponse» dependencies of the studied parameters during Xray test exposure in a dose range of 0.5-3.0 Gy. Nature of the dose curves was determined using linear and linearquadratic regression models. The 3.2 times higher MDA content was found in blood plasma of endometrial cancer patients compared to the control group, namely (60.87 ± 4.93) μM/g of protein versus (18.93 ± 2.05) μM/g of protein (р ≤ 0.05). The raise in MDA content along with increase in the test radiation dose (in a range of 0.5-3.0 Gy) was approximated by the linear regression model Y = 67.44 + 12.52D, R2 = 0.85. A 1.29-1.74fold increase in the mean group value depending on the radiation dose was recorded (р ≤ 0.05). Effects of lowdose irradiation (0.5 Gy) were differentiated as (85.03 ± 8.9) against the initial MDA level of (60.87 ± 4.93) μM/g of protein. There was an increase in the intensity of О2 generation in blood lymphocytes and elevated PAR value in hemolysate from endometrial cancer patients compared to healthy donors by 1.34 and 1.30 times (р ≤ 0.05) respectively, which indicated the intensification of prooxidant processes in patients. The interindividual peculiarities of the blood reactionresponse to radiation were revealed according to parameters depending on the initial values, which characterize them only as additional prognostic biomarkers in radiation treatment planning for gynecological cancer patients. It has been proven that the linear nature of dose dependence of MDA content in blood plasma of endometrial cancer patients and response to lowdose irradiation of are the basic criteria for recognizing MDA as a relevant prognostic biochemical indicator of radiosensitivity of healthy cells from the tumor environment. The content of MDA in blood plasma of gynecological cancer patients should be taken into account in order to identify the subjects with a high risk of radiation complications.

ROS- and Radiation Source-Dependent Modulation of Leukocyte Adhesion to Primary Microvascular Endothelial Cells.

Anti-inflammatory effects of low-dose irradiation often follow a non-linear dose–effect relationship. These characteristics were also described for the modulation of leukocyte adhesion to endothelial cells. Previous results further revealed a contribution of reactive oxygen species (ROS) and anti-oxidative factors to a reduced leukocyte adhesion. Here, we evaluated the expression of anti-oxidative enzymes and the transcription factor Nrf2 (Nuclear factor-erythroid-2-related factor 2), intracellular ROS content, and leukocyte adhesion in primary human microvascular endothelial cells (HMVEC) upon low-dose irradiation under physiological laminar shear stress or static conditions after irradiation with X-ray or Carbon (C)-ions (0–2 Gy). Laminar conditions contributed to increased mRNA expression of anti-oxidative factors and reduced ROS in HMVEC following a 0.1 Gy X-ray and 0.5 Gy C-ion exposure, corresponding to reduced leukocyte adhesion and expression of adhesion molecules. By contrast, mRNA expression of anti-oxidative markers and adhesion molecules, ROS, and leukocyte adhesion were not altered by irradiation under static conditions. In conclusion, irradiation of endothelial cells with low doses under physiological laminar conditions modulates the mRNA expression of key factors of the anti-oxidative system, the intracellular ROS contents of which contribute at least in part to leucocyte adhesion, dependent on the radiation source.

Effects of Low-dose Gamma Radiation on Expression of Apoptotic Genes in Rat Peripheral Blood Lymphocyte.

Background: Exposure to high-dose ionizing radiation is known as a human carcinogen factor, but our information about the effects of low-dose ionizing radiation such as occupational exposures is limited. The main concern of scientific community is biological consequences due to low-dose radiations.Objective: This study aims to evaluate the effects of low-dose γ-radiation on expression changes of apoptotic genes (bax and bcl-2) in the rat peripheral blood lymphocytes.Material and Methods: In this experimental study, 42 adult male rats were classified into 6 groups, which was exposed to various doses values ranged from 20 mGy to 1000 mGy by γ-rays from a Co-60 source. Blood samples were provided for analysis of gene expression 24 h after gamma radiation by relative quantitative Reverse Transcription - Polymerase Chain Reaction (RT-PCR). Radiation sensitivity of rat lymphocytes was measured by the bax/bcl-2 ratio as a predictive marker for radio-sensitivity. Results: The results of this study showed that low dose of gamma radiation can induce down-regulation of bax in rat peripheral blood lymphocytes. Despite other mechanisms of cellular radio-protection, changes in expression of these apoptotic genes can be the primary pathway in responses of the lymphocytes radio-protection to the exposure. Our study revealed a significant decrease in the bax/bcl-2 ratio at 50 mGy dose compare to control and the other irradiated groups (p < 0.05).Conclusion: These results suggest that changes in the bax/bcl-2 ratio especially in radiation workers, as a key factor in apoptosis, can be considered as a biological marker in low-dose gamma radiation.

Comparative analysis of population mortality in the cities of Severodvinsk and Arkhangelsk

Increasing use of ionizing radiation sources in different spheres of human life dictates the need for investigating the effects of low-dose radiation on mortality and morbidity. The aim of this study was to compare mortality from the most common non-communicable diseases in the cities of Severodvinsk and Arkhangelsk. We analyzed the rates of age- and sex-specific mortality from circulatory system diseases (CSD), malignancies, digestive system disorders, respiratory system diseases, and external causes. CSD-related mortality among men and women past working age was higher in Severodvinsk than in Arkhangelsk (median (Q1; Q3): 3,349 (3,271; 3,458) vs 2,651 (2,618; 2,756), p &lt; 0.012; 1,947 (1,890; 2,022) vs 1,753 (1,727; 1,809), p &lt; 0.012; 292 (281; 342) vs 265 (253; 274), p &lt; 0.025, respectively). For other causes of death, mortality rates in Severodvinsk did not exceed those in Arkhangelsk. Increased mortality from CSD in Severodvinsk cannot be linked to socioeconomic conditions or chemical air pollution because the standard of living is higher in Severodvinsk than in Arkhangelsk, whereas the level of chemical pollution is lower. At the same time, the presence of the nuclear shipyard and radioactive waste repository in Severodvinsk could cause chronic exposure to low-dose radiation. It is important to expand preventive measures aimed at early detection of vascular damage in nuclear workers and general groups of population residing in the vicinity of hazardous radiation sites.

External dose reconstruction at the shore of the Metlinsky Pond in the former village of Metlino (Techa River, Russia) based on environmental surveys, luminescence measurements and radiation transport modelling.

The cohorts of people formerly living at the Techa River shoreline in the Southern Urals, Russia, are widely studied cohorts for the investigation of low-dose radiation effects to human health. The nuclear facilities of the Mayak Production Association (PA) discharged their radioactive effluents into the nearby Techa River, especially in the first years of operation. Health status of cohort member data is constantly being improved and updated. Consequently, there is a need to also improve and verify the underlying dosimetry, which gives information about the dose of cohort members. For the Techa River population, the dosimetry is handled in the Techa River Dosimetry System (TRDS). The present work shows results of a feasibility study to validate the TRDS at the location of the village of Metlino, a village just 7km downstream from the Mayak PA. For this settlement there were two sources of external exposure, the contaminated banks of the Techa River and the contaminated shoreline of the nearby Metlinsky Pond. In the present study the north-western wall of a granary was used as a dose archive to validate dose estimates. Measurements of doses in brick accumulated over many decades and measurements of the current dose rate in bricks were combined with dose rate measurements in air above ground in front of the granary, historical contamination data and Monte-Carlo simulations. Air kerma estimates for 1949-1956 significantly different from zero could not be reconstructed for the Metlinsky Pond shoreline near the granary, but an upper dose limit could be estimated. Implications for TRDS-2016 are discussed.

Survival of white blood cells of mice (Mus musculus L) on interval AD with CD post gamma radiation Co-60

One of the phenomena of the low-dose radiation effect is the radio adaptation response which is an important part of the response of molecules, cells, and body tissues to ionizing radiation. The phenomenon of radio adaptation response is a response that occurs when changes in gene expression can be induced by exposure to low doses of radiation (&lt;0.5 Gy). Changes in the expression of this gene under certain circumstances serve to protect cells against the effects caused by subsequent exposure to higher doses of radiation, so this situation is known as an adaptive response or radio adaptation response. Cells can respond to very low doses of radiation with some changes in gene expression. Beginning with the administration of radiation to cells with a very low dose, known as the adaptation dose (AD), and then in a short period being given a larger dose of radiation, known as the challenge dose (CD), there was a decrease in the number of induced chromosome aberrations when compared to cells that were not irradiated at an adapted dose. The purpose of this study was to obtain a radiotherapy method that could show a reduction in the patient's dose.

Ultra-hyper-fractionated radiotherapy for high-grade gliomas.

High-grade gliomas (HGGs; WHO grades III and IV) are invariably lethal brain tumors. Low-dose hyper-radiosensitivity (HRS) of HGG is a well-established phenomenon in vitro. However, possibly linked to the unavailability of accurate animal models of the diseases, this therapeutic effect could not be consistently translated to the animal setting, thus impairing its subsequent clinical development. The purpose of this study was to develop radiotherapeutic (RT) schedules permitting to significantly improve the overall survival of faithful animal models of HGG that have been recently made available. We used primary glioma initiating cell (GIC)-driven orthotopic animal models that accurately recapitulate the heterogeneity and growth patterns of the patients' tumors, to investigate the therapeutic effects of low radiation doses toward HGG. With the same total dose, RT fractions ≤0.5Gy twice per week [ultra-hyper-fractionation (ultra-hyper-FRT)] started at early stages of tumor progression (a condition that in the clinical setting often occurs at the end of the guidelines treatment) improved the effectiveness of RT and the animal survival in comparison to standard fractions. For the same cumulative dose, the use of fractions ≤0.5Gy may permit to escape one or more tumor resistance mechanisms thus increasing the effectiveness of RT and the overall animal survival. These findings suggest investigating in the clinical setting the therapeutic effect of an ultra-hyper-FRT schedule promptly extending the conventional RT component of the current guideline ("Stupp") therapeutic protocol.

Impact of medical imaging on the epigenome – low-dose exposure in the course of computed tomography does not induce detectable changes of DNA-methylation profiles in peripheral blood cells

Background Computed tomography (CT) is a main contributor to artificial low-dose exposure. Understanding the biological effects induced by CT exposure and their dependency on the characteristics of photon spectra is essential for knowledge-driven risk assessment. In a previous gene expression study, we have identified upregulation of AEN, BAX, DDB2, EDA2R and FDXR after ex vivo exposure with single-energy CT and dual-energy CT (DECT). In this study, we focused on CT-induced changes of DNA methylation. This epigenetic modification of DNA is a central regulator of gene expression and instrumental in preserving genome integrity. Previous studies reported focal hypermethylation and global hypomethylation after exposure with doses above 100 mSv, however, the effect of low dose exposure on DNA methylation is hardly explored. Materials and methods DNA was isolated from peripheral blood of three healthy individuals 6 h after ex vivo exposition to single-energy (80 kV and 150 kV) and DECT (80 kV/Sn150 kV) with a calculated effective dose of 7.0 ± 0.08 mSv. The experimental setting was identical to the one used in our previous gene expression study enabling a direct comparison of gene expression results with changes of DNA methylation identified in this study. DNA methylation was analyzed by high-throughput sequencing of bisulfite-treated DNA targeted methylation sequencing. Results Unsupervised hierarchical clustering based on DNA methylation profiles of all samples created three distinct clusters. Formation of these three clusters was solely determined by the origin of samples, indicating the absence of prominent irradiation-associated changes of DNA methylation. In line with this observation, inter-individual comparison of non-irradiated samples revealed 1163, 1224 and 4550 significant differentially methylated regions (DMRs), respectively, whereas the pairwise comparison of irradiated and non-irradiated samples failed to identify irradiation-induced DMRs in any of the three probands. This even applied to the genomic regions harboring AEN, BAX, DDB2, EDA2R and FDXR, the five genes known to be upregulated by CT exposure. Conclusions CT exposure with various photon spectra did not result in detectable changes of DNA methylation. However, minor effects in a subpopulation of irradiated cells cannot be ruled out. Thus, future studies with extended observation intervals are needed to investigate DNA methylation changes that are induced by indirect effects at later points of time or become detectable by clonal expansion of affected cells. Moreover, our data suggest that DNA methylation analysis is less sensitive in detecting immediate effects of low-dose irradiation when compared to gene expression analysis.

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.