Low Doses Of Ionizing Radiation Research Articles

Low-dose ionizing radiation-induced RET/PTC1 rearrangement via the non-homologous end joining pathway to drive thyroid cancer.

Thyroid cancer incidence increases worldwide annually, primarily due to factors such as ionizing radiation (IR), iodine intake, and genetics. Papillary carcinoma of the thyroid (PTC) accounts for about 80% of thyroid cancer cases. RET/PTC1 (coiled-coil domain containing 6 [CCDC6]-rearranged during transfection) rearrangement is a distinctive feature in over 70% of thyroid cancers who exposed to low doses of IR in Chernobyl and Hiroshima‒Nagasaki atomic bombings. This study aims to elucidate mechanism between RET/PTC1 rearrangement and IR in PTC. N-thy-ori-3-1 cells were subjected to varying doses of IR (2/1/0.5/0.2/0.1/0.05Gy) of IR at different days, and result showed low-dose IR-induced RET/PTC1 rearrangement in a dose-dependent manner. RET/PTC1 has been observed to promote PTC both in vivo and in vitro. To delineate the role of different DNA repair pathways, SCR7, RI-1, and Olaparib were employed to inhibit non-homologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ), respectively. Notably, inhibiting NHEJ enhanced HR repair efficiency and reduced IR-induced RET/PTC1 rearrangement. Conversely, inhibiting HR increased NHEJ repair efficiency and subsequent RET/PTC1 rearrangement. The MMEJ did not show a markable role in this progress. Additionally, inhibiting DNA-dependent protein kinase catalytic subunit (DNA-PKcs) decreased the efficiency of NHEJ and thus reduced IR-induced RET/PTC1 rearrangement. To conclude, the data suggest that NHEJ, rather than HR or MMEJ, is the critical cause of IR-induced RET/PTC1 rearrangement. Targeting DNA-PKcs to inhibit the NHEJ has emerged as a promising therapeutic strategy for addressing IR-induced RET/PTC1 rearrangement in PTC.

Investigation of biological-rhythm patterns: physiological and biochemical effects in herbaceous plants exposed to low-level chronic radiation – part 1: nonirradiated seeds

Hypothesis Because reactive oxygen species are involved in the regulation of biological rhythms, we hypothesized that intra-annual variability of seed progeny quality at low doses of ionizing radiation (LDIRs) would differ from that of background plants. Materials and methods We conducted 12 consecutive experiments using the roll culture method by germinating seeds (monthly for 3 weeks) of six herbaceous plant species (Bromus inermis, Geum aleppicum, Plantago major, Rumex confertus, Silene latifolia, and Taraxacum officinale) growing under conditions of chronic radiation in the East Ural Radioactive Trace (EURT). We assessed physiological (seed viability and abnormality frequency) and biochemical (low-molecular-weight antioxidants, LMWAs) parameters of seedlings. Results Total absorbed dose rates of maternal plants (TADRplants) and seed embryos (TADRseeds) in the EURT exceeded background levels by 1–3 and 1–2 orders of magnitude, respectively. Nonlinear dependencies on TADR were mainly characteristic of physiological and biochemical parameters. For most populations of the studied species (B. inermis, G. aleppicum, R. confertus, and S. latifolia), seedling survival and root length decreased in the autumn–winter period, while the frequency of abnormal seedlings increased. The content of LMWAs could be ranked as R. confertus > B. inermis > G. aleppicum > S. latifolia, in good agreement with the presence of anthocyanin pigmentation in the plants. The lowest synthesis of antioxidants in seedlings was observed in winter. A high LMWA content promoted growth and reduced the frequency of abnormal seedlings. Conclusions These results underscore a multistage nature of the impact of LDIRs on intra-annual biological rhythms in plants. High heterogeneity in reference group ‘wild grasses’ and diversity of their radiobiological effects should help to develop methods of radiation protection for natural ecosystems and facilitate approaches used by the International Commission on Radiological Protection. Highlights Absorbed dose rates for six plant species in the East Ural Radioactive Trace (EURT) area range from 0.11 to 73.89 µGy h−s (plants) and 0.11 to 6.88 µGy h−s (seed embryos). Intra-annual rhythms of physiological and biochemical parameters in the EURT zone differ from those in background seedlings. Plants in the EURT area exhibit a wide range of trait variability, asynchrony of the manifestation of the effects, nonlinear dose–response relations, and hormesis. A high content of low-molecular-weight antioxidants (LMWAs) is associated with low frequency of developmental abnormalities and high viability of seed progeny.

Sequential radiation exposure: uncovering the potential of low dose ionizing radiation in mitigating high dose effects on immune cells

Purpose The radioadaptive response refers to a phenomenon wherein exposure to a low dose of ionizing radiation (LDIR) can induce a protective response in cells or organisms, reducing the adverse effects of a subsequent higher dose of ionizing radiation (HDIR). However, it is possible to administer the low dose after the challenge dose. This study was conducted to determine the potential mitigating effect of LDIR administered after HDIR on mice immune cells. Materials and methods Alongside the conventional adaptive response setting, one group of mice was initially exposed to HDIR and subsequently treated with LDIR. Neutrophil activation was done using DHR-reducing assay and cell proliferation was evaluated through CFSE-dilution assay in helper (CD4+) and cytotoxic (CD8+) T cells. Cytokine production by these T cell subsets was also assessed by intracellular staining using flow cytometry. Results The results of this study revealed no change in neutrophil function between any of the mice groups compared to the untreated control group. Although significant changes were not detected in the proliferation of CD4+ T cells, decreased proliferation was observed in stimulated CD8+ T cells in the HDIR group. In contrast to IFN-ɣ, which showed no evident change in either of the T cell subsets after stimulation, IL-4 was rigorously dropped in stimulated CD4+ T cells in the HDIR group. Conclusions In summary, the results of this study indicated that the administration of LDIR to mice before HDIR was not able to reduce the detrimental effects of HDIR in our experimental setting. Instead, we observed a mitigating effect of LDIR when administered after the challenge dose. This suggests that not only the dose and duration but also the order of LDIR relative to HDIR affects its efficacy.

Micronuclei and Gamma-H2AX Detection in Medical Radiation Workers

One of the most harmful DNA lesions brought on by exposure to ionizing radiation (IR) is DNA double-strand breaks. The working duration time may affect the dose accumulation of radiation workers routinely exposed to IR. The study presented here aims to determine the correlation between micronuclei (MN) frequency and γ-H2AX foci index in medical workers who are occupationally exposed to low-dose IR. Peripheral blood lymphocytes were collected from 30 radiation workers that grouped working less and more than 20 years, consisting of radiologists, nurses, cardiologists and radiology technicians. MN frequencies were calculated by analysing 1000 binucleated cells and γ-H2AX foci were calculated by analysing 50 cells. No significant difference was observed between the γ-H2AX foci frequencies and MN indexes when comparing the exposed group with working years ≥20 compared to those working <20 years. Chronic exposure to low-dose IR increases the DNA repair process and reduces micronuclei formation.

Low-Dose Ionizing Radiation-Crosslinking Immunoprecipitation (LDIR-CLIP) Identified Irradiation-Sensitive RNAs for RNA-Binding Protein HuR-Mediated Decay.

Although ionizing radiation (IR) is widely used for therapeutic and research purposes, studies on low-dose ionizing radiation (LDIR) are limited compared with those on other IR approaches, such as high-dose gamma irradiation and ultraviolet irradiation. High-dose IR affects DNA damage response and nucleotide-protein crosslinking, among other processes; however, the molecular consequences of LDIR have been poorly investigated. Here, we developed a method to profile RNA species crosslinked to an RNA-binding protein, namely, human antigen R (HuR), using LDIR and high-throughput RNA sequencing. The RNA fragments isolated via LDIR-crosslinking and immunoprecipitation sequencing were crosslinked to HuR and protected from RNase-mediated digestion. Upon crosslinking HuR to target mRNAs such as PAX6, ZFP91, NR2F6, and CAND2, the transcripts degraded rapidly in human cell lines. Additionally, PAX6 and NR2F6 downregulation mediated the beneficial effects of LDIR on cell viability. Thus, our approach provides a method for investigating post-transcriptional gene regulation using LDIR.

Genome-wide study reveals novel roles for formin-2 in axon regeneration as a microtubule dynamics regulator and therapeutic target for nerve repair

Peripheral nerves regenerate successfully; however, clinical outcome after injury is poor. We demonstrated that low-dose ionizing radiation (LDIR) promoted axon regeneration and function recovery after peripheral nerve injury (PNI). Genome-wide CpG methylation profiling identified LDIR-induced hypermethylation of the Fmn2 promoter, exhibiting injury-induced Fmn2 downregulation in dorsal root ganglia (DRGs). Constitutive knockout or neuronal Fmn2 knockdown accelerated nerve repair and function recovery. Mechanistically, increased microtubule dynamics at growth cones was observed in time-lapse imaging of Fmn2-deficient DRG neurons. Increased HDAC5 phosphorylation and rapid tubulin deacetylation were found in regenerating axons of neuronal Fmn2-knockdown mice after injury. Growth-promoting effect of neuronal Fmn2 knockdown was eliminated by pharmaceutical blockade of HDAC5 or neuronal Hdac5 knockdown, suggesting that Fmn2deletion promotes axon regeneration via microtubule post-translational modification. In silico screening of FDA-approved drugs identified metaxalone, administered either immediately or 24-h post-injury, accelerating function recovery. This work uncovers a novel axon regeneration function of Fmn2 and a small-molecule strategy for PNI.

People do not have high levels of knowledge of low dose ionizing radiation (LDIR)

Through survey and focus groups in two provinces in Canada misunderstanding and confusion surrounding Low-Dose Ionizing Radiation (LDIR) is explored specifically surrounding medical procedures, risk, and benefits. Generally people associated the word radiation with harm, but when asked participants were not concerned about LDIR. Approximately equal numbers (40%) thought LDIR was ‘difficult’ as those that thought it was ‘easy’ but research results reveal confusion about the definition of and sources of LDIR. Most people believed the benefits of LDIR outweighed the risks. Further, many had inaccurate views of ‘high’ dose radiation. Scientists and the Canadian regulator were determined to be the most trusted sources of information while elected officials and industry representatives the least trusted. Participants wanted more information on whether LDIR was a problem in Canada, what the risks were associated with it, as well as the applicable protections, rules and regulations. Focus group participants expressed a preference for face-to-face exchange of information, but mass media remains an important source of information as the first-place people check for answers. Future research surrounding behavioural science and LDIR communications, and deep LDIR science communication will be important in addressing this issue.

Exposure to low-dose radiation in occupational settings and ischaemic heart disease: a systematic review and meta-analysis

Ionising radiation is a human carcinogen, but the evidence is less clear that exposure to low-dose ionising radiation (LDIR) increases the risk of adverse cardiovascular outcomes. We synthesised the literature...

New Facets of DNA Double Strand Break Repair: Radiation Dose as Key Determinant of HR versus c-NHEJ Engagement.

Radiation therapy is an essential component of present-day cancer management, utilizing ionizing radiation (IR) of different modalities to mitigate cancer progression. IR functions by generating ionizations in cells that induce a plethora of DNA lesions. The most detrimental among them are the DNA double strand breaks (DSBs). In the course of evolution, cells of higher eukaryotes have evolved four major DSB repair pathways: classical non-homologous end joining (c-NHEJ), homologous recombination (HR), alternative end-joining (alt-EJ), and single strand annealing (SSA). These mechanistically distinct repair pathways have different cell cycle- and homology-dependencies but, surprisingly, they operate with widely different fidelity and kinetics and therefore contribute unequally to cell survival and genome maintenance. It is therefore reasonable to anticipate tight regulation and coordination in the engagement of these DSB repair pathway to achieve the maximum possible genomic stability. Here, we provide a state-of-the-art review of the accumulated knowledge on the molecular mechanisms underpinning these repair pathways, with emphasis on c-NHEJ and HR. We discuss factors and processes that have recently come to the fore. We outline mechanisms steering DSB repair pathway choice throughout the cell cycle, and highlight the critical role of DNA end resection in this process. Most importantly, however, we point out the strong preference for HR at low DSB loads, and thus low IR doses, for cells irradiated in the G2-phase of the cell cycle. We further explore the molecular underpinnings of transitions from high fidelity to low fidelity error-prone repair pathways and analyze the coordination and consequences of this transition on cell viability and genomic stability. Finally, we elaborate on how these advances may help in the development of improved cancer treatment protocols in radiation therapy.

The impact of ionizing radiation compared to drug-induced immunological changes.

Ionizing radiation (IR) activates several signaling pathways. This study shows the impact of acute low-dose IR on crucial cytokines involved in cell-mediated immunity. The immunomodulatory effects of 0.25 and 0.5 Gray (Gy) gamma rays and standard immunomodulatory drugs (cyclophosphamide) on blood counts and significant pro-inflammatory cytokines implicated in various inflammatory conditions were tested in 20 rats. Examined was the effect of acute low doses on critical cytokines, which could be utilized as an alternative to current immunosuppressive drugs. One day post-irradiation, serum levels of interferon-gamma (INF-γ), tumor necrosis factor-alpha, and interleukin-2/1-beta were measured. A 0.25Gy exposure did not affect the detected cytokines or blood cell count compared to the nonirradiated group. On the other hand, 0.5Gy raises the majority of the immunologically examined cytokines except for INF-γ. Except for INF-γ, cyclophosphamide reduces all of the cytokines examined. As a result, low-dose IR has a less negative influence on essential inflammatory cytokines, permitting its use. More research is needed to determine how low amounts could be used in different immunological disorders.

Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory response after brain injury and stroke

Traumatic brain injury (TBI) and stroke share a common pathophysiology that worsens over time due to secondary tissue injury caused by sustained inflammatory response. However, studies on pharmacological interventions targeting the complex secondary injury cascade have failed to show efficacy. Here, we demonstrated that low-dose ionizing radiation (LDIR) reduced lesion size and reversed motor deficits after TBI and photothrombotic stroke. Magnetic resonance imaging demonstrated significant reduction of infarct volume in LDIR-treated mice after stroke. Systems-level transcriptomic analysis showed that genes upregulated in LDIR-treated stoke mice were enriched in pathways associated with inflammatory and immune response involving microglia. LDIR induced upregulation of anti-inflammatory- and phagocytosis-related genes, and downregulation of key pro-inflammatory cytokine production. These findings were validated by live-cell assays, in which microglia exhibited higher chemotactic and phagocytic capacities after LDIR. We observed substantial microglial clustering at the injury site, glial scar clearance and reversal of motor deficits after stroke. Cortical microglia/macrophages depletion completely abolished the beneficial effect of LDIR on motor function recovery in stroke mice. LDIR promoted axonal projections (brain rewiring) in motor cortex and recovery of brain activity detected by electroencephalography recordings months after stroke. LDIR treatment delayed by 8 h post-injury still maintained full therapeutic effects on motor recovery, indicating that LDIR is a promising therapeutic strategy for TBI and stroke.

Effects of low-dose ionizing radiation on genomic instability in interventional radiology workers

Interventional radiologists are chronically exposed to low-dose ionizing radiation (IR), which may represent a health risk. The aim of the present study was to evaluate genomic instability by analyzing chromosomal aberrations, micronuclei, and 53BP1 DNA repair foci in peripheral blood lymphocytes of radiologists. Based on the IAEA guidelines on biodosimetry using dicentrics, the average protracted whole-body dose in radiologists were estimated. Since preleukemic fusion genes (PFG) are the primary events leading to leukemia, we also studied their presence by RT-qPCR and FISH. No significant difference in 53BP1 foci and incidence of PFG (MLL-AF4, MLL-AF9, AML1-ETO, BCR-ABL p190) was found in cells of interventional radiologists in comparison to controls. However, our results showed an increased frequency of micronuclei and various types of chromosomal aberrations including dicentrics in interventional radiologists. The average protracted whole body estimated dose was defined at 452.63 mGy. We also found a significantly higher amplification of the MLL gene segment and increased RNA expression in cells of interventional radiologists in comparison to controls. In conclusion, our results showed that long-term low-dose IR induces genomic instability in interventional radiologists.

Low‑dose ionizing radiation attenuates high glucose‑induced hepatic apoptosis and immune factor release via modulation of a miR‑155‑SOCS1 axis.

Diabetic liver injury (DLI) can result in several diseases of the liver, including steatohepatitis, liver fibrosis, cirrhosis, and liver cancer. Low‑dose ionizing radiation (LDIR) has hormetic effects in normal/disease conditions. However, whether LDIR has a beneficial effect on DLI has not been assessed previously. MicroRNA (miR)‑155 and its target gene suppressor of cytokine signaling 1 (SOCS1) play critical roles in modulating hepatic proliferation, apoptosis, and immunity. However, whether a miR‑155‑SOCS1 axis is involved in high glucose (HG) induced hepatic damage remains to be determined. In the present study, mouse hepatocyte AML12 cells were treated with 30mM glucose (HG), 75 mGy X‑ray (LDIR), or HG plus LDIR. The expression levels of miR‑155 and SOCS1 were determined by reverse transcription‑quantitative PCR and western blotting. Additionally, apoptosis was measured using flow cytometry. The release of inflammatory factors, including TNF‑α, IL‑1β, IL‑6, IL‑10, and IFN‑γ, after HG and/or LDIR treatment was detected by ELISA. The results showed that HG may induce hepatic apoptosis by upregulating the levels of miR‑155 and downregulating the levels of SOCS1. HG also stimulated the secretion of TNF‑α, IL‑1β, IL‑6, and IL‑10. However, LDIR blocked the HG‑induced activation of a miR‑155‑SOCS1 axis and suppressed the release of inflammatory factors. These results indicated that a miR‑155‑SOCS1 axis plays a role in HG‑induced liver injury, and LDIR may exert a hepatoprotective effect by regulating the miR‑155‑SOCS1 axis.

The impact of cyclophosphamide versus high-level of ionizing radiation on the immune response

The immune response to various high doses of Ionizing Radiation (IR) is investigated in this study compared to the non-irradiated group and other immunosuppressive conditions. Thirty rats were divided into six different groups. Group I received no radiation or medications. Groups II, III, IV, and V were subjected to the entire body to 1, 2, 3, and 5 Gray (Gy) of IR. Cyclophosphamide 50 mg/kg was administered intraperitoneally to Group VI. Serum levels of Interleukin-2/1-beta, Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (INF-γ) were measured one day after irradiation. The immunosuppressive effect of cyclophosphamide reduced the majority of the evaluated parameters. When high doses of IR, notably greater than 1Gy, were investigated, all measured parameters increased consistently. Finally, high doses of IR amplify essential pro-inflammatory responses and cannot be used to suppress the immune system in a single dose. More research is needed to clarify immune responses and their therapeutic potential in response to high or low IR doses.

Evaluation of micronuclei and antioxidant status in hospital radiation workers occupationally exposed to low-dose ionizing radiation

PurposeThere is scientific evidence that ionizing radiation (IR) can be responsible for various health hazards that are one of the concerns in occupational exposure. This study was performed to evaluate DNA damage and antioxidant status in hospital workers who are occupationally exposed to low doses of IR.Materials and methodsIn this study, twenty occupationally exposed to low doses of IR (CT and angiography) comprising with control groups which matched them. In order to investigate the effects of chronic irradiation of radiation workers, Micronuclei (MN) frequency and the antioxidant activity of Superoxide Dismutase (SOD), Catalase (CAT) and Total Antioxidant Capacity (TAC) were measured. Then, to check adaptation against high challenge dose, the samples (in all groups) were irradiated in vitro and MN frequency was compared. Finally, to investigated the effect of the high dose after the acute and chronic low dose of ionizing radiation, MN frequency was compared in two groups (the control group that was to in-vitro irradiated (acute low dose + high dose) and radiation workers (chronic low dose + high dose)).ResultsMN frequency in the occupationally exposed group (n = 30) increased significantly when compared to the control group (p-value < 0.0001). However, chronic irradiation of radiation workers could not lead to an adaptive Sresponse, while acute low-doses could produce this effect (p-value ˂ 0.05). In addition, the activity levels of antioxidant enzymes SOD, CAT, and TAC were not statistically different between the radiation workers and the control group (p-value > 0.05).ConclusionsWe observed that exposure to low doses of IR leads to increased cytogenetic damage, could not cause an adaptive-response, and improve antioxidant capacity in radiation workers. Controlling healthcare workers' exposure is the first step to improving the health of hospital workers and the quality of patient care, thus decreasing human and economic costs.

Lympho-hematopoietic malignancies risk after exposure to low dose ionizing radiation during cardiac catheterization in childhood.

Pediatric patients with congenital heart disease (CHD) often undergo low dose ionizing radiation (LDIR) from cardiac catheterization (CC) for the diagnosis and/or treatment of their disease. Although radiation doses from a single CC are usually low, less is known about the long-term radiation associated cancer risks. We aimed to assess the risk of lympho-hematopoietic malignancies in pediatric CHD patients diagnosed or treated with CC. A French cohort of 17,104 children free of cancer who had undergone a first CC from 01/01/2000 to 31/12/2013, before the age of 16 was set up. The follow-up started at the date of the first recorded CC until the exit date, i.e., the date of death, the date of first cancer diagnosis, the date of the 18th birthday, or the 31/12/2015, whichever occurred first. Poisson regression was used to estimate the LDIR associated cancer risk. The median follow-up was 5.9 years, with 110,335 person-years. There were 22,227 CC procedures, yielding an individual active bone marrow (ABM) mean cumulative dose of 3.0 milligray (mGy). Thirty-eight incident lympho-hematopoietic malignancies were observed. When adjusting for attained age, gender and predisposing factors to cancer status, no increased risk was observed for lympho-hematopoietic malignancies RR/mGy = 1.00 (95% CI: 0.88; 1.10). In summary, the risk of lympho-hematopoietic malignancies and lymphoma was not associated to LDIR in pediatric patients with CHD who undergo CC. Further epidemiological studies with greater statistical power are needed to improve the assessment of the dose-risk relationship.

Immediate effects of acute Mars mission equivalent doses of SEP and GCR radiation on the murine gastrointestinal system-protective effects of curcumin-loaded nanolipoprotein particles (cNLPs).

Missions beyond low Earth orbit (LEO) will expose astronauts to ionizing radiation (IR) in the form of solar energetic particles (SEP) and galactic cosmic rays (GCR) including high atomic number and energy (HZE) nuclei. The gastrointestinal (GI) system is documented to be highly radiosensitive with even relatively low dose IR exposures capable of inducing mucosal lesions and disrupting epithelial barrier function. IR is also an established risk factor for colorectal cancer (CRC) with several studies examining long-term GI effects of SEP/GCR exposure using tumor-prone APC mouse models. Studies of acute short-term effects of modeled space radiation exposures in wildtype mouse models are more limited and necessary to better define charged particle-induced GI pathologies and test novel medical countermeasures (MCMs) to promote astronaut safety. In this study, we performed ground-based studies where male and female C57BL/6J mice were exposed to γ-rays, 50 MeV protons, or 1 GeV/n Fe-56 ions at the NASA Space Radiation Laboratory (NSRL) with histology and immunohistochemistry endpoints measured in the first 24 h post-irradiation to define immediate SEP/GCR-induced GI alterations. Our data show that unlike matched γ-ray controls, acute exposures to protons and iron ions disrupts intestinal function and induces mucosal lesions, vascular congestion, epithelial barrier breakdown, and marked enlargement of mucosa-associated lymphoid tissue. We also measured kinetics of DNA double-strand break (DSB) repair using gamma-H2AX- specific antibodies and apoptosis via TUNEL labeling, noting the induction and disappearance of extranuclear cytoplasmic DNA marked by gamma-H2AX only in the charged particle-irradiated samples. We show that 18 h pre-treatment with curcumin-loaded nanolipoprotein particles (cNLPs) delivered via IV injection reduces DSB-associated foci levels and apoptosis and restore crypt villi lengths. These data improve our understanding of physiological alterations in the GI tract immediately following exposures to modeled space radiations and demonstrates effectiveness of a promising space radiation MCM.

Combined effect of simulated microgravity and low-dose ionizing radiation on structure and antibiotic resistance of a synthetic community model of bacteria isolated from spacecraft assembly room

Understanding the structural and antibiotic resistance changes of microbial communities in space environments is critical for identifying potential pathogens that may pose health risks to astronauts and for preventing and controlling microbial contamination. The research to date on microbes under simulated space factors has primarily been carried out on single bacterial species under the individual effects of microgravity or low-dose radiation. However, microgravity (MG) and low-dose ionizing radiation (LDIR) coexist in the actual spacecraft environment, and microorganisms coexist as communities in the spacecraft environment. Thus, the microbial response to the real changes present during space habitation has not been adequately explored. To address this knowledge gap, we compared the dynamics of community composition and antibiotic resistance of synthetic bacterial communities under simulated microgravit, low-dose ionizing radiation, and the conditions combined, as it occurs in spacecraft. To ensure representative bacteria were selected, we co-cultured of 12 bacterial strains isolated from spacecraft cleanrooms. We found that the weakened competition between communities increased the possibility of species coexistence, community diversity, and homogeneity. The number of Bacilli increased significantly, while different species under the combined conditions showed various changes in abundance compared to those under the individual conditions. The resistance of the synthetic community to penicillins increased significantly under low doses of ionizing radiation but did not change significantly under simulated microgravity or the combined conditions. The results of functional predictions revealed that antibiotic biosynthesis and resistance increased dramatically in the community under space environmental stress, which confirmed the results of the drug sensitivity assays. Our results show that combined space environmental factors exert different effects on the microbial community structure and antibiotic resistance, which provides new insights into our understanding of the mechanisms of evolution of microorganisms in spacecraft, and is relevant to effective microbial pollution prevention and control strategies.

Evaluation of Changes in Some Functional Properties of Human Mesenchymal Stromal Cells Induced by Low Doses of Ionizing Radiation.

Each person is inevitably exposed to low doses of ionizing radiation (LDIR) throughout their life. The research results of LDIR effects are ambiguous and an accurate assessment of the risks associated with the influence of LDIR is an important task. Mesenchymal stromal cells (MSCs) are the regenerative reserve of an adult organism; because of this, they are a promising model for studying the effects of LDIR. The qualitative and quantitative changes in their characteristics can also be considered promising criteria for assessing the risks of LDIR exposure. The MSCs from human connective gingiva tissue (hG-MSCs) were irradiated at doses of 50, 100, 250, and 1000 mGy by the X-ray unit RUST-M1 (Russia). The cells were cultured continuously for 64 days after irradiation. During the study, we evaluated the secretory profile of hG-MSCs (IL-10, IDO, IL-6, IL-8, VEGF-A) using an ELISA test, the immunophenotype (CD45, CD34, CD90, CD105, CD73, HLA-DR, CD44) using flow cytometry, and the proliferative activity using the xCelligence RTCA cell analyzer at the chosen time points. The results of study have indicated the development of stimulating effects in the early stages of cultivation after irradiation using low doses of X-ray radiation. On the contrary, the effects of the low doses were comparable with the effects of medium doses of X-ray radiation in the long-term periods of cultivation after irradiation and have indicated the inhibition of the functional activity of MSCs.

Exposure of Shewanella oneidensis MR-1 to Sublethal Doses of Ionizing Radiation Triggers Short-Term SOS Activation and Longer-Term Prophage Activation.

Currently, there is a lack of bacterial biomarkers indicative of exposure to ionizing radiation (IR). IR biomarkers have applications for medical treatment planning, population exposure surveillance, and IR sensitivity studies. In this study, we compared the utility of signals originating from prophages and the SOS regulon as biomarkers of IR exposure in the radiosensitive bacterium Shewanella oneidensis. Using RNA sequencing, we demonstrated that 60 min after exposure to acute doses of IR (40, 1, 0.5, and 0.25 Gy), the transcriptional activation of the SOS regulon and the lytic cycle of the T-even lysogenic prophage So Lambda are comparable. Using quantitative PCR (qPCR), we showed that 300 min after exposure to doses as low as 0.25 Gy, the fold change of transcriptional activation of the So Lambda lytic cycle surpassed that of the SOS regulon. We observed an increase in cell size (a phenotype of SOS activation) and plaque production (a phenotype of prophage maturation) 300 min after doses as low as 1 Gy. While the transcriptional responses of the SOS and So Lambda regulons have been examined in S. oneidensis after lethal IR exposures, the potential of these (and other transcriptome-wide) responses as biomarkers of sublethal levels of IR (<10 Gy) and the longer-term activity of these two regulons have not been investigated. A major finding is that after exposure to sublethal doses of IR, the most upregulated transcripts are associated with a prophage regulon and not with a DNA damage response. Our findings suggest that prophage lytic cycle genes are a promising source of biomarkers of sublethal DNA damage. IMPORTANCE The bacterial minimum threshold of sensitivity to ionizing radiation (IR) is poorly understood, which hinders our understanding of how living systems recover from the doses of IR experienced in medical, industrial, and off-world environments. Using a transcriptome-wide approach, we studied how in the highly radiosensitive bacterium S. oneidensis, genes (including the SOS regulon and the So Lambda prophage) are activated after exposure to low doses of IR. We found that 300 min after exposure to doses as low as 0.25 Gy, genes within the So Lambda regulon remained upregulated. As this is the first transcriptome-wide study of how bacteria respond to acute sublethal doses of IR, these findings serve as a benchmark for future bacterial IR sensitivity studies. This is the first work to highlight the utility of prophages as biomarkers of exposure to very low (i.e., sublethal) doses of IR and to examine the longer-term impacts of sublethal IR exposure on bacteria.