Acute Irradiation Research Articles

528 Energy metabolism rewiring following acute UVB irradiation is largely dependent on nuclear DNA damage

Solar ultraviolet B (UVB) radiation is the main risk factor of skin carcinoma via the induction of DNA damage like cyclobutane pyrimidine dimers (CPD). Cells respond to UVB irradiation with a series of signaling cascades called DNA damage response (DDR), which are necessary for maintaining cell integrity. DDR involves sensing the damage and subsequently signaling to downstream effectors. This network includes different cell signaling pathways such as DNA repair systems or apoptosis, however, its crosstalk with energy metabolism is still unclear. To elucidate the link between DDR and energy metabolism, we took advantage of keratinocytes expressing nuclear or mitochondrial CPD photolyases. Applying comprehensive proteomic analysis and metabolomics, we found a biphasic alteration in numerous metabolic pathways (such as glycolysis, oxidative phosphorylation, fatty acid B-oxidation) after acute exposure of keratinocyte to UVB radiation, which was largely dependent on nuclear DNA damage. Using live imaging and bioinformatic analyses, we found that the structure of the mitochondrial network was dynamically modified after UVB irradiation and those modifications were affected by both mitochondrial and nuclear DNA damage. Altogether, our data suggest that energy metabolism could be considered as a sub-program of the DDR network. A better understanding of what role metabolism plays in keratinocyte responses to UVB radiation is crucial for developing adapted metabolic therapies both for prevention and therapy of skin cancers.

Arabidopsis thaliana Accessions from the Chernobyl Exclusion Zone Show Decreased Sensitivity to Additional Acute Irradiation.

Chronic ionising radiation exposure is a main consequence of radioactive pollution of the environment. The development of functional genomics approaches coupled with morphological and physiological studies allows new insights into plant adaptation to life under chronic irradiation. Using morphological, reproductive, physiological, and transcriptomic experiments, we evaluated the way in which Arabidopsis thaliana natural accessions from the Chernobyl exclusion zone recover from chronic low-dose and acute high-dose γ-irradiation of seeds. Plants from radioactively contaminated areas were characterized by lower germination efficiency, suppressed growth, decreased chlorophyll fluorescence, and phytohormonal changes. The transcriptomes of plants chronically exposed to low-dose radiation indicated the repression of mobile genetic elements and deregulation of genes related to abiotic stress tolerance. Furthermore, these chronically irradiated natural accessions showed higher tolerance to acute 150 Gy γ-irradiation of seeds, according to transcriptome and phytohormonal profiles. Overall, the lower sensitivity of the accessions from radioactively contaminated areas to acute high-dose irradiation may come at the cost of their growth performance under normal conditions.

Morphological and electrophysiological changes of retina after different light damage in three patients: Three case reports

Light-induced retinal damage is a serious vision-threatening disease, resulting from unsuitable laser irradiation, high-power light and sustaining light exposure. Therefore, effectively evaluate the morphological and functional of retinal damage is urgently needed. Now, we mainly reported three patients suffered from typical light irradiations. Patient 1 suffered from old laser pointer irradiation and followed with amblyopia treatment. Patient 2 suffered from acute high-energy light irradiation. Patient 3 suffered from sustaining optical fiber irradiation. Detailed morphological and functional examinations of the retina revealed that the lesions of the three patients had many similar characteristics, such as macular morphological changes, patent pattern visual monitoring amplitude or peak time abnormalities, multi-fucus electroretinograms macular central amplitude density decreased. In conclusion, light-induced retinopathy has many common features, which can help clinical medical staff to diagnose retinal photodamage diseases.

Long-Term Immunological Consequences of Radiation Exposure in a Diverse Cohort of Rhesus Macaques

The aim of this study was to develop an improved understanding of the delayed immunologic effects of acute total body irradiation (TBI) using a diverse cohort of nonhuman primates as a model for an irradiated human population. Immune recovery was evaluated in 221 rhesus macaques either left unirradiated (n=36) or previously irradiated (n=185) at 1.1 to 8.5 Gy TBI (median, 6.5 Gy) when aged 2.1 to 15.5 years (median, 4.2 years). Blood was drawn annually for up to 5 years total between 0.5 and 14.3 years after exposure. Blood was analyzed by complete blood count, immunophenotyping of monocytes, dendritic cells (DC) and lymphocytes by flow cytometry, and signal joint T-cell receptor exclusion circle quantification in isolated peripheral blood CD4 and CD8 T cells. Animals were categorized by age, irradiation status, and time since irradiation. Sex-adjusted means of immune metrics were evaluated by generalized estimating equation models to identify cell populations altered by TBI. Overall, the differences between irradiated and nonirradiated animals were subtle and largely restricted to younger animals and select cell populations. Subsets of monocytes, DC, T cells, and B cells showed significant interaction effects between radiation dose and age after adjustment for sex. Irradiation at a young age caused transient increases in the percentage of peripheral blood myeloid DC and dose-dependent changes in monocyte balance for at least 5 years after TBI. TBI also led to a sustained decrease in the percentage of circulating memory B cells. Young irradiated animals exhibited statistically significant and prolonged disruption of the naïve/effector memory/central memory CD4 and CD8 T-cell equilibrium and exhibited a dose-dependent increase in thymopoiesis for 2 to 3 years after exposure. This study indicates TBI subtly but significantly alters the circulating proportions of cellular mediators of adaptive immune memory for several years after irradiation, especially in macaques under 5 years of age and those receiving a high dose of radiation.

Radiation-induced electrophysiological remodelling in neonatal rat ventricular cardiomyocytes

Abstract Background Ventricular tachycardia (VT) carries a relatively high risk of recurrence and significantly impacts patients' quality of life, despite state of the art treatment including antiarrhythmic drug therapy and catheter ablation. Cardiac stereotactic body radiotherapy (SBRT) has emerged as a promising non-invasive treatment option for refractory VT. A marked reduction in VT episodes is observed within days of treating high-risk patients with a single fraction SBRT. The cellular mechanisms underlying the clinically demonstrated antiarrhythmic effect are still poorly understood. Radiation-induced fibrosis is observed several months after irradiation, suggesting other mechanisms that explain the immediate benefit of radiotherapy on the VT substrate. Purpose We hypothesized that early antiarrhythmic effects of single-fraction radiation are produced by direct molecular and functional electrophysiological changes, independent of fibrosis. Our aim was to investigate the effects of 20 Gy ionizing photon radiation on the electrophysiology of ventricular neonatal rat cardiomyocytes at time periods from 24 hours to 96 hours after irradiation. Methods Ventricular neonatal rat cardiomyocytes were isolated, cultivated for 24 to 96 hours and then exposed to photon beam with a single dose of 20 Gy. Expression changes of ion channels, calcium handling proteins and structural proteins affecting cellular electrophysiology were assessed via RT-qPCR and Western blotting. Beat frequency was evaluated by video analysis and action potentials (APD) were recorded using the whole-cell voltage clamp technique in current-clamp mode. Intracellular calcium transients in Fura-2 AM loaded cardiomyocytes were recorded with an IonOptix recording system. Results Irradiation lead to significant changes in the mRNA and protein level of ion channels, with most distinct changes being observed 96h after radiation. Increased mRNA and protein expression of (Cav1.2) and of the potassium channels Kcnd3 (Kv4.3), Kcnh2 (Kv11.1), Kcnq1 (Kv7.1), Kcnk2 (K2P2.1) and Kcnj2 (Kir2.1) was observed. Additionally, Connexin 43 (Cx43) was upregulated. Irradiated cardiomyocytes showed a significant increase in beat rate over time. APD was significantly shortened, with a significantly increased upstroke velocity. Regarding calcium handling, significant upregulations of Ryr2 (RYR2) and Slc8a1 (NCX) transcript and protein level was detected. Additionally, calcium handling properties were altered. Conclusion Our results suggest that acute irradiation effects are associated with electrophysiological remodelling in cardiomyocytes. Changes of cellular ion channel expression and calcium homeostasis lead to normalization and shortening of heart-failure associated APD prolongation. These results reveal new insights into acute antiarrhythmic effects on cardiomyocytes after SBRT-therapy. Funding Acknowledgement Type of funding sources: None.

Limited mutagenesis of myelokaryocytes following acute external irradiation as a protective mechanism of miliacin in radiation-induced immunosuppression

Antimutagenic effect of the plant triterpenoid miliacin was studied, in order to characterize its protective properties in a model of acute irradiation immunosuppression using outbred male mice. Ionizing irradiation at different doses (0.5; 1.0; 2.0; 4.0 Gy) was used for experimental (miliacin-treated), and control animals that received the miliacin solvent. Miliacin was administered three times intraperitoneally at a single dose of 4.0 mg/kg with 24-hour intervals between injections. The last dose was applied 1 day before irradiation. Myelokaryocytes served as test objects, the analysis of which was carried out 24 hours after irradiation. Miliacin had a certain protective effect by limiting the post-radiation myeloablation, reducing the number of aberrant cells and the total number of aberrations. Protective effect of triterpenoids showed inverse relation to the radiation dose, being most pronounced at the dose of 0.5 Gy. Higher values of chromatid aberrations at radiation doses of 1.0 and 2.0 Gy in animals from the experimental group versus control mice, probably, due to anti-apoptotic effect of the triterpenoid, thus ensuring higher survival rates of mutated cells with severe damage to their genome. The protective effect of miliacin at 24 hours after radiation exposure may indicate its effect on the primary radiochemical stage of radiation injury. It is suggested that the mechanism of protective action of triterpenoid is mediated by its previously shown antioxidant activity, due to its ability to stabilize membranes and normalize expression of genes encoding antioxidant protection enzymes. Thus, the antimutagenic activity of miliacin after irradiation is an important characteristic of its immunoprotective effect during the radiation-induced immunosuppression. With respect to its ability to limit the mutagenic effect, miliacin may be classified as a weak radioprotective antimutagen with a protection efficiency of 20-40% at the dose range of 0.5 to 1.0 Gray.

New Properties of a Well-Known Antioxidant: Pleiotropic Effects of Human Lactoferrin in Mice Exposed to Gamma Irradiation in a Sublethal Dose.

We studied the effects of human lactoferrin (hLf), a multifunctional protein from the transferrin family, on integral (survival, lifespan during the experiment, body weight, behavior, subfractional compositions of blood serum) and systemic (hemoglobin level, leukocyte number, differential leukocyte count, histological structure of the liver and spleen) parameters of the body in mice after acute gamma irradiation in a sublethal dose. The experiments were performed on male C57BL/6 mice. The mice in the experimental groups were exposed to whole-body gamma radiation in a dose of 7.5 Gy from a 60Co source. Immediately after irradiation and 24 h after it, some animals received an intraperitoneal injection of hLf (4 mg/mouse). Single or repeated administration of hLf had a positive pleiotropic effect on irradiated animals: animal survival increased from 28% to 78%, and the mean life expectancy during the experiment (30 days) increased from 16 to 26 days. A compensatory effect of hLf on radiation-induced body weight loss, changes in homeostasis parameters, and a protective effect on the structural organization of the spleen were demonstrated. These data indicate that Lf has potential as a means of early therapy after radiation exposure.

Beneficial Effect of Gastrodia elata Blume and Poria cocos Wolf Administration on Acute UVB Irradiation by Alleviating Inflammation through Promoting the Gut-Skin Axis.

Bioactive compounds in some herbs can, directly and indirectly, protect against photoaging. We evaluated the effects of Gastrodia elata Blume (GE) and Poria cocos Wolf (PC) water extracts on ultraviolet (UV) B-induced skin lesions by acute UVB exposure in ICR mice and explored their mechanism of action. After removing the hair on the back of the mice, UVB (280–310 nm) was exposed to the back for 30 min to induce skin damage. Four UVB exposure groups were divided into the following according to the local application (1,3-butanediol extract) on the dorsal skin and oral intake (0.3 g water extract/kg body weight/day): 1,3-butanediol and cellulose(control; UV-Con), retinoic acid (positive-control; UV-Positive), PC extracts (UV-PC), and GE extracts (UV-GE). The fifth group had no UVB exposure with the same treatment as the UV-Con (Normal-control). The erythema, burns, erosion, and wounds of the UV-PC and UV-PC groups were alleviated, and the most significant improvements occurred in the UV-PC group. PC and GE reduced the thickness of the dorsal skin tissue, the penetration of mast cells, and malondialdehyde contents. The mRNA expression of TNF-α, IL-13, and IL-4, inflammatory factors, were also reduced significantly in the dorsal skin of the UV-PC and UV-GE groups. UV-PC, UV-GE, and UV-Positive showed improvements in UV-induced intestinal tissue inflammation. UV-Con deteriorated the intestinal morphology, and PC and GE alleviated it. The α-diversity of the fecal microbiota decreased in the UV-control, and UV-PC and UV-GE prevented the decrease. Fecal metagenome analysis revealed increased propionate biosynthesis in the UV-PC group but decreased lipopolysaccharide biosynthesis in the UV-PC and UV-GE groups compared to UV-Con. In conclusion, the local application and intake of PC and GE had significant therapeutic effects on acute UV-induced skin damage by reducing oxidative stress and proinflammatory cytokines, potentially promoting the gut-microbiota-gut-skin axis.

STUDY OF BIOLOGICAL EFFECTS OF TRITIUM IN MICE.

The mutation, apoptosis and chromosomal aberration induced by tritiated water (HTO) in spleen T lymphocytes of mice were investigated and compared with those by acute or chronic 137Cs gamma irradiation. p53 wild-type (p53+/+) and null (p53-/-) mice were exposed to tritium (3H) beta rays via a single injection of HTO. 137Cs gamma irradiation was carried out at dose-rate of 0.86Gy min-1 (acute) and at a low dose-rate (0.71-0.09mGy min-1) that mimicked internal exposure (gamma simulation-irradiation). Each dose of irradiation was 3Gy. When compared on the basis of the induced TCR variant fractions in p53-/- mice at 3Gy, 3H beta rays appeared to be more mutagenic than chronic gamma ray reference. On the other hand, both of the frequency chromosomal aberration was not different significantly between HTO injected and 137Cs gamma irradiated mice.

Dynamics of Dopamine and Other Monoamines Content in Rat Brain after Single Low-Dose Carbon Nuclei Irradiation

Space radiation, presented primarily by high-charge and -energy particles (HZEs), has a substantial impact on the central nervous system (CNS) of astronauts. This impact, surprisingly, has not only negative but also positive effects on CNS functions. Despite the fact that the mechanisms of this effect have not yet been elucidated, several studies indicate a key role for monoaminergic networks underlying these effects. Here, we investigated the effects of acute irradiation with 450 MeV/n carbon (12C) nuclei at a dose of 0.14 Gy on Wistar rats; a state of anxiety was accessed using a light–dark box, spatial memory in a Morris water maze, and the dynamics of monoamine metabolism in several brain morphological structures using HPLC. No behavioral changes were observed. Irradiation led to the immediate suppression of dopamine turnover in the prefrontal cortex, hypothalamus, and striatum, while a decrease in the level of norepinephrine was detected in the amygdala. However, these effects were transient. The deferred effect of dopamine turnover increase was found in the hippocampus. These data underscore the ability of even low-dose 12C irradiation to affect monoaminergic networks. However, this impact is transient and is not accompanied by behavioral alterations.

Printing Polymeric Convex Lenses to Boost the Sensitivity of a Graphene-Based UV Sensor.

Ultraviolet (UV) is widely used in daily life as well as in industrial manufacturing. In this study, a single-step postprocess to improve the sensitivity of a graphene-based UV sensor is studied. We leverage the advantage of electric-field-assisted on-demand printing, which is simply applicable for mounting functional polymers onto various structures. Here, the facile printing process creates optical plano-convex geometry by accelerating and colliding a highly viscous droplet on a micropatterned graphene channel. The printed transparent lens refracts UV rays. The concentrated UV photon energy from a wide field of view enhances the photodesorption of electron-hole pairs between the lens and the graphene sensor channel, which is coupled with a large change in resistance. As a result, the one-step post-treatment has about a 4× higher sensitivity compared to bare sensors without the lenses. We verify the applicability of printing and the boosting mechanism by variation of lens dimensions, a series of UV exposure tests, and optical simulation. Moreover, the method contributes to UV sensing in acute angle or low irradiation. In addition, the catalytic lens provides about a 9× higher recovery rate, where water molecules inside the PEI lens deliver fast reassembly of the electron-hole pairs. The presented method with an ultimately simple fabrication step is expected to be applied to academic research and prototyping, including optoelectronic sensors, energy devices, and advanced manufacturing processes.

ОСОБЕННОСТИ ОПУХОЛЕВЫХ КЛЕТОК ЧЕЛОВЕКА ЛИНИИ HeLa,ВЫЖИВШИХ И ДАВШИХ УСТОЙЧИВЫЙ РОСТ ПОСЛЕ ОСТРОГО РЕНТГЕНОВСКОГО ОБЛУЧЕНИЯ

Purpose: The evaluation of the repair efficiency of DNA double-strand breaks (DSB), proliferative activity and the yield of cytogenetic disorders in human tumor HeLa cells which survived and gave stable growth after acute irradiation at a dose of 15 Gy. Material and methods: HeLa human tumor cell line (cervical carcinoma) was used. Cells were irradiated on an X-ray biological installation RUST-M1 (Russia), equipped with two X-ray emitters, at a dose rate of 0.85 Gy / min, a voltage of 200 kV, a total current of 10 mA, and a 1.5 mm Al filter. To obtain clones of surviving cells (HeLaRR), after acute irradiation at a dose of 15 Gy, cell cultures were incubated under standard CO2 incubator conditions (37 °C, 5 % CO2) for several weeks until well proliferating cells were obtained. Immunocytochemical staining of the foci of the phosphorylated H2AX protein (γH2AX) was used to quantitatively evaluate the residual foci of DNA DSB repair. The micronuclei number was assessed in cytochalasin-B cytokinesis-blocked binucleated cells stained with acridine orange with luminescence microscopy. The doubling time of the cell population was analyzed by the cell growth curves obtained by daily cell counting for five days. The cell cycle stages distribution was assessed by flow cytometry using the propidium iodide dye. All quantitative indicators of the studies were processed using the Student’s t-test for independent samples and the Kolmogorov – Smirnov test. Results: It was revealed that acute irradiation at a high dose leads to the selection of cells with a higher reparative capacity which is confirmed by the low yield of residual foci of DNA DSB repair and MN after testing irradiation at doses of 5 and 10 Gy. A significant decrease in the proliferative activity of cells that survived after acute X-ray irradiation at a dose of 15 Gy was revealed. The doubling time of the population of unirradiated cells at the stage of exponential growth was ~18 hours while for cells that survived after irradiation at a dose of 15 Gy ~42 hours. A change in the cell cycle phases distribution was observed. Conclusion: Thus, acute irradiation at a high dose leads to the selection of cells with a higher reparative capacity which is confirmed by the low yield of residual γH2AX foci and MN after testing irradiation at doses of 5 and 10 Gy. The decrease in proliferative activity was accompanied by a change in the cell cycle phases distribution.

Resolving the acute gamma irradiation and ethyl methanesulphonate induced lethality for Jasminum sambac L. (Aiton) cv. Ramanathapuram Gundumalli

Crop improvement in Jasminum sambac through induced mutagenesis entails the insight on the sensitiveness of the individual plant materials of a species to different classes and nature of the mutagens. The current assessment was undertaken to analyse the mutagenic effect of acute gamma irradiation and EMS in Jasminum sambac cv. Ramanathapuram Gundumalli. Semi-hardwood cuttings of the plants were exposed to different dosage levels of gamma rays varying from 0 Gy (control) to 40 Gy and decapitated rooted cuttings were treated with EMS from 0 mM (control) to 90 mM. The M1V1 generation was evaluated by treating the cuttings with four different doses of gamma rays (15 Gy, 20 Gy, 25 Gy and 30 Gy) and three concentrations of EMS (45 mM, 60 mM, 75 mM) formulated using respective LD50 doses.  The lethality dosage (LD50) value for the cultivar Ramanathapuram Gundumalli was determined to be 21.37 Gy and 64.57 mM for gamma irradiation and EMS, respectively applying the probit curve analysis. The maximal reduction in the survival of cuttings of 75% and 71% correspondingly in gamma and EMS treatments was discerned at higher doses in comparison to the lower doses. The plants studied in M1V1 generation for growth and flowering characters exhibited variable responses pertaining to differing doses or concentrations of the specific mutagenic means. Keywords: Jasminum sambac, gamma irradiation, EMS, LD50 and semi-hardwood cuttings

Influence of the irradiation geometry on the severity of acute radiation damage

The aim of this study was to demonstrate how the severity of radiation damage in the case of bone marrow syndrome due to acute irradiation depends on the non-uniform irradiation of the body. We used the calculation method that involves the evaluation of organism mortality as a function of bone marrow cells colony survival vs dose for different radiation profiles. It was presumed that the probability of the death for the organism is the same for the same value of survival level of the bone marrow cells regardless of the dose distribution by mass of the organ. The dose of uniform irradiation that is equivalent to the dose for the L-th case of non-uniform irradiation is calculate based on the survival level of the total marrow cells. After that the probability of the death of the organism is estimated according to the dose response curve. Dose distribution in bone marrow of computational MIRD-5-type stylized model adult man for different geometries of exposure by point source of 137Cs was evaluated. Larger non-uniformity of the dose distribution in the bone marrow at the same dose in free air in the site of human location causes a greater probability of survival due to a greater proportion of bone marrow cells that have preserved the possibility of reproduction. The values of mean 50% lethal dose for cases of approximately uniform irradiation of the body surface (point source at a distance 10m) and sharply non-uniform irradiation (point source at a distance of 0.5 m) differ approximately by the factor of 1.7 – 2.5 depending on direction of irradiation. Additionally the values of conversion coefficients from the reading of an individual dosimeter to the value of an effective dose for various geometries of irradiation of emergency workers from the 137Cs point source were calculated. The average value of the conversion coefficient from personal dose to effective dose for the considered exposure situations is 0.7 Sv Cy-1 and the 90% confidence interval is 0.49 – 0.99 Sv Gy-1.

Differential gene expression in chronically irradiated herbaceous species from the Chernobyl exclusion zone

Purpose Transcriptional activity of genes related to ionizing radiation responses in chronically irradiated plant populations at radioactively contaminated territories can be a cost-effective and precise approach for stress response evaluation. However, there are limits to studying non-model plants in field conditions. The work studies the transcriptional activity of candidate genes of adaptation to chronic radiation exposure in plant populations from radioactively contaminated territories of the Chernobyl. Materials and methods In this work, we studied plant species with different sensitivity to acute irradiation: Trifolium repens L., Taraxacum officinale Wigg., and Dactylis glomerata L., sampled in the Chernobyl exclusion zone. The differential expression of several candidate genes of adaptation to chronic radiation exposure in the leaves of these species was analyzed, including homologs of Arabidopsis thaliana genes SLAC1, APX1, GPX2, CAB1, NTRB, PP2-B11, RBOH-F, HY5, SnRK2.4, PDS1, CIPK20, SIP1, PIP1, TIP1. Results and conclusions All studied species were characterized by upregulation of the CAB1 homolog, encoding chlorophyll a/b binding protein, at radioactively contaminated plots. An increase in the expression of genes associated with water and hydrogen peroxide transport, intensity of photosynthesis, and stress responses (homolog of aquaporin TIP1 for T. repens; homologs of aquaporin PIP1 and transcription factor HY5 for D. glomerata; homolog of CBL-interacting serine/threonine protein kinase CIPK20 for T. officinale) was revealed. The methodological approach for studying gene expression in non-model plant species is described, which may allow large-scale screening studies of candidate genes in various plant species abundant in radioactively contaminated areas.

Chronic infrared-A irradiation-induced photoaging of human dermal fibroblasts from different donors at physiological temperature.

In this study, we examined cellular responses to acute and chronic IRA irradiation at mild and natural levels of exposure in two types of human fibroblasts, each isolated from a different donor, at physiological temperature (34°C). Two types of human dermal fibroblasts (derived from a 20- and 50-year-old women, respectively) were exposed to different repeat numbers of IRA exposure (3, 6, 10, and 14 times; 42 mW/cm2 ) at a frequency of 3-4 times per week (4h per irradiation). Cellular responses to acute and chronic IRA irradiation were examined by reactive oxygen species (ROS) level, apoptotic signals, cellular morphology, and collagen level. We demonstrated that chronic IRA irradiation-induced severe cellular damage, including prolonged cell proliferation, increased intracellular ROS levels, activated cellular apoptosis, and elongated cell morphology, whereas acute IRA irradiation had negligible effects at 34°C. In addition, it was evident that the degree of cellular damage due to IRA irradiation differed according to the type of fibroblasts. Considering the severe cellular damage induced by chronic IRA irradiation without heat, continuous exposure of skin to IRA irradiation during daily life may be harmful enough to induce photoaging.

Comparative characteristics of morphological changes in the pancreas under different types of irradiation in the experiment

The aim of the study was to conduct a comparative characteristic of the morphological changes in the pancreas with different types of irradiation in the experiment. It has been established that a comparative description of the data of the first (acute irradiation) and the second group (chronic irradiation) of white outbred rats revealed 11 morphological signs indicating pathological changes in the pancreatic parenchyma, in terms of the intensity of occurrence of which differences were found that related to such morphological changes as atrophic changes in the interlobular excretory duct, stromal fatty degeneration, which were visualized only in animals of the first group. Plasma impregnation of vessel walls, atrophic changes in the parenchyma, atrophy of the islets of Langerhans were not found in all animals of the second group, while in the first group they were visualized in all rats. Comparative analysis shows that pathological changes in the pancreatic parenchyma of animals treated with acute irradiation were more intense, and more pathological signs were seen compared to chronic irradiation.

Low-Dose Gamma Radiation Modulates Liver and Testis Tissues Response to Acute Whole Body Irradiation.

AimThis work aims to investigate whether the pre-exposure to low dose/low dose rate (40 mGy, 2.2 mGy/hour) γ-radiation as a priming dose can produce a protective effect against the subsequent high one (4 Gy, .425 Gy/minute).MethodsRats were divided into Group I (control), Group II (L); exposed to 40 mGy, Group III (H); exposed to 4 Gy, and Group IV (L+H); exposed to 40 mGy 24 hours before the exposure to 4Gy. The molecular and biochemical changes related to oxidative stress, DNA damage, apoptosis, and mitochondrial activity in the liver and testis were studied 4 hours after irradiation.ResultsExposure to 40 mGy before 4 Gy induced a significant increase in the levels of Nrf2, Nrf2 mRNA, TAC, and mitochondrial complexes I & II accompanied by a significant decrease in the levels of LPO, 8-OHdG, DNA fragmentation, TNF-α, caspase-3, and caspase-3 mRNA compared with H group.ConclusionExposure to low-dose γ-radiation before a high dose provides protective mechanisms that allow the body to survive better after exposure to a subsequent high one via reducing the oxidative stress, DNA damage, and apoptosis-induced early after irradiation. However, further studies are required to identify the long-term effects of this low dose.

Radiobiological features in offspring of natural populations of Drosophila melanogaster after Chernobyl accident.

In their natural habitats, populations of organisms are faced with different levels of chronic low-intensity radiation, causing a wide range of radiobiological effects (from radiosensitivity to radioadaptive response and hormesis). In this study, specimens of Drosophila melanogaster were selected from territories of the Chernobyl nuclear power plant with different levels of radioactive contamination. The isogenic stocks derived from these specimens represent the genetic systems of current populations and make it possible to study radioresistance and its mechanisms in future generations under controlled laboratory conditions. Previous studies have shown that transgenerational radiation effects at the level of lethal mutations and survival rate are unstable and depend not only on the level of chronic low-intensity irradiation, but also on other factors. A single acute irradiation exposure of offspring whose parents inhabited a site with a higher level of chronic irradiation made it possible to reveal pronounced radioresistant features in the offspring. And the offspring whose parents were exposed to radiation levels close to the natural radiation background, on the contrary, acquired radiosensitive features. Their response to acute exposure includes a high-frequency of lethal mutations and a short lifespan. The differential response to different levels of chronic parental exposure is caused by differences in the activities of certain transposons that destabilize the genome. Our data contribute to the understanding of genetic and epigenetic mechanisms (via transposon activity) of the effect of parental radiation exposure on the health and adaptive potential of populations affected by the technogenically increased radiation background.

Thioredoxin Reductase 1 Modulates Pigmentation and Photobiology of Murine Melanocytes in vivo

Pigment-producing melanocytes overcome frequent oxidative stress in their physiological role of protecting the skin against the deleterious effects of solar UV irradiation. This is accomplished by the activity of several endogenous antioxidant systems, including the thioredoxin antioxidant system, in which thioredoxin reductase 1 (TR1) plays an important part. To determine whether TR1 contributes to the redox regulation of melanocyte homeostasis, we have generated a selective melanocytic Txnrd1-knockout mouse model (Txnrd1mel‒/‒), which exhibits a depigmentation phenotype consisting of variable amelanotic ventral spotting and reduced pigmentation on the extremities (tail tip, ears, and paws). The antioxidant role of TR1 was further probed in the presence of acute neonatal UVB irradiation, which stimulates melanocyte activation and introduces a spike in oxidative stress in the skin microenvironment. Interestingly, we observed a significant reduction in overall melanocyte count and proliferation in the absence of TR1. Furthermore, melanocytes exhibited an elevated level of UV-induced DNA damage in the form of 8-oxo-2'-deoxyguanosine after acute UVB treatment. We also saw an engagement of compensatory antioxidant mechanisms through increased nuclear localization of transcription factor NRF2. Altogether, these data indicate that melanocytic TR1 positively regulates melanocyte homeostasis and pigmentation during development and protects against UVB-induced DNA damage and oxidative stress.