Effects Of Low-dose Ionizing Radiation Research Articles

Investigation into Chronic Low-Dose Ionizing Radiation Effect on Gene Expression Profile of Human HUVECs Cells.

Introduction: Understanding the molecular mechanism of chronic low-dose ionizing radiation (LDIR) effects on the human body is the subject of many research studies. Several aspects of cell function such as cell proliferation, apoptosis, inflammation, and tumorigenesis are affected by LDIR. Detection of the main biological process that is targeted by LIDR via network analysis is the main aim of this study. Methods: GSE66720 consisting of gene expression profiles of human umbilical vein endothelial cells (HUVECs) (a suitable cell line to be investigated), including irradiated and control cells, was downloaded from Gene Expression Omnibus (GEO). The significant differentially expressed genes (DEGs) were determined and analyzed via protein-protein interaction (PPI) network analysis to find the central individuals. The main cell function which was related to the central nodes was introduced. Results: Among 64 queried DEGs, 48 genes were recognized by the STRING database. C-X-C motif chemokine ligand 8 (CXCL8), intercellular adhesion molecule 1 (ICAM1), Melanoma growth-stimulatory activity/growth-regulated protein α (CXCL1), vascular cell adhesion molecule 1 (VCAM-1), and nerve growth factor (NGF) were introduced as hub nodes. Conclusion: Findings indicate that inflammation is the main initial target of LDIR at the cellular level which is associated with alteration in the other essential functions of the irradiated cells.

Low dose ionizing radiation effects on the immune system

Ionizing radiation interacts with the immune system in many ways with a multiplicity that mirrors the complexity of the immune system itself: namely the need to maintain a delicate balance between different compartments, cells and soluble factors that work collectively to protect, maintain, and restore tissue function in the face of severe challenges including radiation damage. The cytotoxic effects of high dose radiation are less relevant after low dose exposure, where subtle quantitative and functional effects predominate that may go unnoticed until late after exposure or after a second challenge reveals or exacerbates the effects. For example, low doses may permanently alter immune fitness and therefore accelerate immune senescence and pave the way for a wide spectrum of possible pathophysiological events, including early-onset of age-related degenerative disorders and cancer. By contrast, the so called low dose radiation therapy displays beneficial, anti-inflammatory and pain relieving properties in chronic inflammatory and degenerative diseases. In this review, epidemiological, clinical and experimental data regarding the effects of low-dose radiation on the homeostasis and functional integrity of immune cells will be discussed, as will be the role of immune-mediated mechanisms in the systemic manifestation of localized exposures such as inflammatory reactions. The central conclusion is that ionizing radiation fundamentally and durably reshapes the immune system. Further, the importance of discovery of immunological pathways for modifying radiation resilience amongst other research directions in this field is implied.

Oxidized Cell-Free DNA Is a Factor of Stress Signaling in Radiation-Induced Bystander Effects in Different Types of Human Cells

In pathology or under damaging conditions, the properties of cell-free DNA (cfDNA) change. An example of such change is GC enrichment, which drastically alters the biological properties of cfDNA. GC-rich cfDNA is a factor of stress signaling, whereas genomic cfDNA is biologically inactive. GC-rich cfDNA stimulates TLR9-MyD88-NF-κB signaling cascade, leading to an increase in proinflammatory cytokine levels in the organism. In addition, GC-rich DNA is prone to oxidation and oxidized cfDNA can stimulate secondary oxidative stress. This article is a review of works dedicated to the investigation of a low-dose ionizing radiation effect, a bystander effect, and the role of cfDNA in both of these processes.

Cataractogenic load - A concept to study the contribution of ionizing radiation to accelerated aging in the eye lens.

Ionizing radiation (IR) damages DNA and other macromolecules, including proteins and lipids. Most cell types can repair DNA damage and cycle continuously their macromolecules as a mechanism to remove defective proteins and lipids. In those cells that lack nuclei and other organelles, such as lens fiber cells and mammalian erythrocytes, IR-induced damage to macromolecules is retained because they cannot be easily replenished. Whilst the life span for an erythrocyte is several months, the life span of a human lens is decades. There is very limited turnover in lens macromolecules, therefore the aging process greatly impacts lens structure and function over its lifetime. The lens is a tissue where biomolecular longevity, lifelong retention of its components and continued growth are integral to its homeostasis. These characteristics make the lens an excellent model to study the contribution of retained macromolecular damage over time. Epidemiological data have revealed a significant association between exposure to IR, the loss of lens optical function and the formation of cataracts (cataractogenesis) later in life. Lifestyle, genetic and environmental factors all contribute to cataractogenesis due to their effect on the aging process. Cataract is an iconic age-related disease in humans. IR is a recognised cause of cataract and the occupational lens dose limit is reduced from 150 to 20 mGy / year averaged over 5 years (ICRP Publication 118). Understanding the effects of low dose IR on the lens and its role in cataractogenesis is therefore very important. So we redefine "cataractogenic load" as a term to account for the combined lifestyle, genetic and environmental processes that increase biomolecular damage to lens macromolecules leading to cataract formation. These processes weaken metabolic defenses, increase post-translational protein modifications, and alter the lipid structure and content of the lens. IR exposure is a significant insult to the lens because of free radical generation and the ensuing oxidative stress. We support the concept that damage caused by IR compounds the aging process by increasing the cataractogenic load, hereby accelerating lens aging and its loss of function.

Intermittent low dose irradiation enhances the effectiveness of radio-therapy for human breast adenocarcinoma cell line MDA–MB–231

Introduction: Hormesis and adaptive responses are two important biological effects of low-dose ionizing radiation (LDIR) in organism and mammalian cell lines. Notably, LDIR generates distinct biological effects in cancer cells from normal cells, e.g., it may affect the growth of cancer cells via the activation of certain cell signaling pathway, which does not exist in normal cells. Therefore, LDIR is considered as a promising assistant method of clinical cancer therapy. Materials and Methods: In order to investigate the intermittent LDIR effect on breast cancer, MDA–MB–231 cells were divided into four experimental groups. Group A, cells were irradiated in 10 fractions with a dose of 30 mGy at each one. The time interval between two irradiations was 24h. Group B, were cultured simultaneously for the same10 days and received a dose of 300 mGy and subsequently a high dose of 2 Gy after 24h. Group C, accepted a single high dose of 2 Gy. Group D was mock irradiation group as control. We examined cell proliferation activity using MTT assay and PI-Annexin V kit to assay cell apoptosis after 24 hours of last irradiation dose (2Gy). Also we used RT-PCR to examine the cell cycle arrest and apoptosis pathway. For this purpose we examined p21 and cespase3 genes in this study. Results: The intermittent LDIR increased cell apoptosis up to 32.55% and in other groups, apoptosis were 30.14%, 25.49% and 8.37% in single LDIR, HDIR and control group respectively. The apoptosis percentages were markedly higher than in the intermittent LDIR groups (P<0.01). Through the cell growth assays, we observed that 300 mGy intermittent LDIR significantly increased the killing effect of radiotherapy (viability: 71.95%) (P<0.01). Although apoptosis in intermittent LDIR was the highest (32.55%) in comparison with other groups, the expression of caspase3 gene in this group was the lowest (1.42fold), 4.26fold and 5.2 fold in single LDIR and HDIR respectively. On the other, the expression of p21 gene, which plays the role of cell cycle arresting, was the lowest in intermittent LDIR group (1.21fold) which suggests that low dose of radiation can reduce the expression of p21 gene and promotes cell cycle in damaged cell and finally causes the death of cancer cells. Conclusion: Intermittent LDIR followed by HDIR are a novel strategy to improve radiotherapy efficiency and could be combined with other therapeutic modalities for cancer treatments. Low dose has a different mechanism for killing cancer cells, therefore, it has no killing effect on normal cells.

Correction: Low-dose ionizing radiation exposure represses the cell cycle and protein synthesis pathways in in vitro human primary keratinocytes and U937 cell lines.

[This corrects the article DOI: 10.1371/journal.pone.0199117.].

Low Dose Radiation Exposure and Cardiovascular Diseases: A Review

ICRP stated that particular attention should be paid to radiation effects in the cardiovascular system because of recent published observations of radiation effects in this systems occurring after much lower doses than reported previously (ICRP, 2007 and 2012). The review was based on scientific articles available in the open literature, major reviews by other organizations, in particular International Commission on Radiation Protection (ICRP, 118). In this review, we describe low-dose ionizing radiation effect, causes of cardiovascular diseases, relationship between low-dose ionizing radiation and cardiovascular diseases, as well as the importance and urgent of elucidate the relationship between low dose ionizing radiation and cardiovascular disease.

Identification of cellular responses to low-dose radiation by the profiling of phosphorylated proteins in human B-lymphoblast IM-9 cells

Purpose: The aim of this study was to explore the potential for radiation-specific signaling of various LDIR-induced effects in human B-lymphoblast IM-9 cells.Materials and methods: Human lymphoblast IM-9 cells were exposed to ionizing radiation at 0.1 and 2 Gy using a 137Cs γ-irradiator at a dose rate of 0.8 Gy/min. Cell viability and DNA fragmentation were determined using MTT assay and TUNEL assay at 24 h after irradiation. Profiling of protein phosphorylation by radiation was identified using a phospho-antibody array at 4 h after irradiation and Dataset of the profiling was analyzed by IPA.Results: Cell survival and apoptotic signaling were not affected by 0.1 Gy of radiation, whereas 2 Gy induced cellular damage. The analysis of low-dose ionizing radiation (LDIR) or high-dose ionizing radiation (HDIR)-specific responses by IPA generated different results. Various cell maintenance functions were only apparent following the analysis of increased protein phosphorylation by LDIR, whereas several cancer formation- and development-related functions were only detected following the analysis of increased protein phosphorylation by HDIR.Conclusions: The LDIR-induced protein phosphorylation patterns might be involved in various cell survival responses or cellular maintenance functions, which provide important insight into our understanding of the different effects of LDIR and HDIR.

Evaluation of low dose ionizing radiation effect on some blood components in animal model

Exposure to ionizing radiation is known to have lethal effects in blood cells. It is predicted that an individual may spend days, weeks or even months in a radiation field without becoming alarmed. The study aimed to discuss the evaluation of low dose ionizing radiation (IR) effect on some blood components in animal model. Hematological parameters were determined for 110 animal rats (divided into 8 groups) pre- and post-irradiation. An attempt to explain the blood changes resulting from both irradiation and time is given. There was a significant reduction in WBC counts one day after irradiation at all dose levels compared to the control group and started to be affected at the dose of 0.3 Gy. The significance was increasing with increasing the dose. The degradation rate was 15 times higher than the recovery rate. Although both rates increase with increasing the dose, however, the rate of recovery in the second stage is faster than that in the initial stage. Platelet count shows a slow increase in the rate of recovery with increasing the dose up to 0.4 Gy. After which there is a linear increase up to a dose of 1 Gy with a slope of 21 count/day/Gy. Additionally, there is an increase in the rate of degradation on the applied dose up to 0.3 Gy with a slope of 61.6 count/day/Gy. The recovery rate of red blood cells count (RBC) increases with the increase in the dose reaching a maximum at about 0.5 Gy. Further increase in dose resulted in a rapid degradation with a minimum count at the dose of 0.75 Gy at the maximum value of 0.5 Gy, the change in count decreases exponentially with the increase in time.The present findings suggest that damage from IR causes a significant reduction in blood cell counts in a dose-dependent manner, which may be considered a potential health risk during exposure to irradiation. Much effort must be done and focused on establishment of protocols for medical management of radiation injuries based on hematopoietic changes for biodosimetry.

Ionizing Particle Radiation as a Modulator of Endogenous Bone Marrow Cell Reprogramming: Implications for Hematological Cancers

Exposure of individuals to ionizing radiation (IR), as in the case of astronauts exploring space or radiotherapy cancer patients, increases their risk of developing secondary cancers and other health-related problems. Bone marrow (BM), the site in the body where hematopoietic stem cell (HSC) self-renewal and differentiation to mature blood cells occurs, is extremely sensitive to low-dose IR, including irradiation by high-charge and high-energy particles. Low-dose IR induces DNA damage and persistent oxidative stress in the BM hematopoietic cells. Inefficient DNA repair processes in HSC and early hematopoietic progenitors can lead to an accumulation of mutations whereas long-lasting oxidative stress can impair hematopoiesis itself, thereby causing long-term damage to hematopoietic cells in the BM niche. We report here that low-dose 1H- and 56Fe-IR significantly decreased the hematopoietic early and late multipotent progenitor (E- and L-MPP, respectively) cell numbers in mouse BM over a period of up to 10 months after exposure. Both 1H- and 56Fe-IR increased the expression of pluripotent stem cell markers Sox2, Nanog, and Oct4 in L-MPPs and 10 months post-IR exposure. We postulate that low doses of 1H- and 56Fe-IR may induce endogenous cellular reprogramming of BM hematopoietic progenitor cells to assume a more primitive pluripotent phenotype and that IR-induced oxidative DNA damage may lead to mutations in these BM progenitors. This could then be propagated to successive cell lineages. Persistent impairment of BM progenitor cell populations can disrupt hematopoietic homeostasis and lead to hematologic disorders, and these findings warrant further mechanistic studies into the effects of low-dose IR on the functional capacity of BM-derived hematopoietic cells including their self-renewal and pluripotency.

Quantitative Proteomic Profiling of Low-Dose Ionizing Radiation Effects in a Human Skin Model.

To assess responses to low-dose ionizing radiation (LD-IR) exposures potentially encountered during medical diagnostic procedures, nuclear accidents or terrorist acts, a quantitative proteomic approach was used to identify changes in protein abundance in a reconstituted human skin tissue model treated with 0.1 Gy of ionizing radiation. To improve the dynamic range of the assay, subcellular fractionation was employed to remove highly abundant structural proteins and to provide insight into radiation-induced alterations in protein localization. Relative peptide quantification across cellular fractions, control and irradiated samples was performing using 8-plex iTRAQ labeling followed by online two-dimensional nano-scale liquid chromatography and high resolution MS/MS analysis. A total of 107 proteins were detected with statistically significant radiation-induced change in abundance (>1.5 fold) and/or subcellular localization compared to controls. The top biological pathways identified using bioinformatics include organ development, anatomical structure formation and the regulation of actin cytoskeleton. From the proteomic data, a change in proteolytic processing and subcellular localization of the skin barrier protein, filaggrin, was identified, and the results were confirmed by western blotting. This data indicate post-transcriptional regulation of protein abundance, localization and proteolytic processing playing an important role in regulating radiation response in human tissues.

Low-dose ionizing radiation effects on differentiation of HL-60 cells

Abstract The biological effects of low-dose radiation have attracted attention, but data are currently insufficient to fully understand the beneficial role of the phenomenon. In the present study, we have investigated the effects of low doses of gamma-irradiation alone and in combination with all-trans-retinoic acid (RA) on proliferation, apoptosis and differentiation of the human promyelocytic leukemia HL-60 cells. Changes in cell behavior and protein expression were determined with the use of light and fluorescent microscopy, immunocytochemical and Western blot analysis. Low-dose irradiation with 1–100 cGy caused a dose-dependent inhibition of HL-60 cell proliferation, and induced apoptosis and differentiation to granulocytes with an increase in the number of CD15-positive cells. Pre-irradiation with 1–100 cGy for 24 h before treatment with RA promoted apoptosis but did not impair RA-induced differentiation. Both processes were associated with a decrease in the expression of the proliferating cell nuclear antigen (PCNA), BCL-2, c-MYC, and changes in both cytosolic and nuclear levels of protein tyrosine-phosphorylation as well as protein kinase C alpha or beta isoforms. These results demonstrate the beneficial role of low-dose irradiation in modulating leukemia cell proliferation, differentiation and apoptosis.

Adaptive Response and Radiosensitivity at Low Doses

Some problems are hindrances to an adequate estimate of low-dose ionizing radiation effects on humans. The most important issue is the lack of a precise definition of the term “low doses”. Radiobiological experiments deal with the dose range of one or more centigrams but their results are often extrapolated to the situations in radio-contaminated regions where extra doses do not exceed 1 mSv; therefore, the concepts are substituted. In epidemiological investigations radiological effects appear at doses above 20 cGy, thereby indicating the inexactitude of the extrapolation of experimental data on the human population. The Adaptive Response (AR) phenomenon is often referred to as an argument, when discussing radiation effects on a human being. Some researchers, in particular, the opponents to the linear non-threshold conception, consider this phenomenon as an evidence of “useful” effects of low-dose radiation. Other investigators, using a play upon words, associate the AR lack in the cells of individuals who were previously irradiated by low doses with potential negative changes in their health. In their expert opinion, it certifies that low doses are extremely hazardous. The authors of this paper analyze some AR peculiarities described in their own earlier articles or in numerous publications of other researches. Irradiation conditions affect the AR induction of one and the same person. Any change in the experimental protocol may provoke the AR loss or even bring to sensitization after the preliminary irradiation. The cells of some individuals from the human population do not develop the AR during standard researches; however, these persons might lack the “appropriate” protocol. The AR potential induction is genetically determined. The AR lack is observed in the cells of the patients with chromosome instability syndromes characterized by extreme radiosensitivity values in the human population. It is also of interest that cell radiosensitivity increases only in abnormal cells of the DS patient with a mosaic form of the disease while the AR is lacking in the both cell lines. Therefore, the level of control and the mechanisms of these processes differ. The AR phenomenon cannot be presently used as a screening test during cytogenetic investigations in contaminated regions as its mechanisms still remain unrevealed, while its manifestation depends on experimental conditions.

Mutation induction after low-dose carbon-ion beam irradiation of frozen human cultured cells

To study the genetic influence of low-dose ionizing radiation at the chromosomal level, frozen human lymphoblastoid TK6 cells were exposed to a 10 cGy dose delivered by a carbon-ion (24.5 ± 2.0 keV/μm) beam. Mutation assays were performed within a few days or after about one month of preservation at -80°C following irradiation. The results showed an increase in mutation frequencies at the thymidine kinase (TK) gene locus of 1.6-fold (2.5 × 10-6 to 3.9 × 10-6) and 2.1-fold (2.5 × 10-6 to 5.3 × 10-6), respectively. The relative distributions of the observed mutation classes were not changed by the radiation exposure in either assay. Multilocus analysis using two TK locus markers and eleven microsatellite loci spanning chromosome 17 were used for the analysis of TK mutants exhibiting a loss of heterozygosity (LOH). An interesting characteristic was detected using this system; interstitial deletion patterns were observed in hemizygous LOH mutants, which were specific for radiation exposure, and considered to be the result of end-joining repair of carbon-ion-induced DNA double-strand breaks. The relative increase in TK mutation frequency of the irradiated cells after the longer preservation at -80°C is probably due to the lower cell-viability compared to the unirradiated level. These results clearly demonstrate that this type of analysis can be used for the detection of low-dose ionizing radiation effects in frozen cells.

“Chernobyl cystitis” induced by chronic low dose ionizing radiation effect through oxidative stress

“Chernobyl cystitis” induced by chronic low dose ionizing radiation effect through oxidative stress

On the biological effects of cosmic rays: epidemiological studies.

Determining the biological effects of cosmic rays and other natural ionizing radiations, could possibly help us in shedding light on the more general problem of low-dose ionizing-radiation effects. In this work we provide a survey of the most recent studies available on epidemiological methods: we discuss the main difficulties in using these methods, as well as the discrepancies in their results.