Cellular Radiation Effects Research Articles

Longitudinal multi-omic changes in the transcriptome and proteome of peripheral blood cells after a 4 Gy total body radiation dose to Rhesus macaques

BackgroundNon-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days and at the cytogenetic level out to 56 days after exposure. We combine the global transcriptomic and proteomic responses in peripheral whole blood to assess the impact of acute TBI exposure at extended times post irradiation.ResultsThe overall mRNA response in the first week reflects a strong inflammatory reaction, infection response with neutrophil and platelet activation. At 1 week, cell cycle arrest and re-entry processes were enriched among mRNA changes, oncogene-induced senescence and MAPK signaling among the proteome changes. Influenza life cycle and infection pathways initiated earlier in mRNA and are reflected among the proteomic changes during the first week. Transcription factor proteins SRC, TGFβ and NFATC2 were immediately induced at 1 day after irradiation with increased transcriptional activity as predicted by mRNA changes persisting up to 1 week. Cell counts revealed a mild / moderate hematopoietic acute radiation syndrome (H-ARS) reaction to irradiation with expected lymphopenia, neutropenia and thrombocytopenia that resolved within 30 days. Measurements of micronuclei per binucleated cell levels in cytokinesis-blocked T-lymphocytes remained high in the range 0.27–0.33 up to 28 days and declined to 0.1 by day 56.ConclusionsOverall, we show that the TBI 4 Gy dose in NHPs induces many cellular changes that persist up to 1 month after exposure, consistent with damage, death, and repopulation of blood cells.

Comparison of the Medical Uses and Cellular Effects of High and Low Linear Energy Transfer Radiation.

Exposure to ionizing radiation can occur during medical treatments, from naturally occurring sources in the environment, or as the result of a nuclear accident or thermonuclear war. The severity of cellular damage from ionizing radiation exposure is dependent upon a number of factors including the absorbed radiation dose of the exposure (energy absorbed per unit mass of the exposure), dose rate, area and volume of tissue exposed, type of radiation (e.g., X-rays, high-energy gamma rays, protons, or neutrons) and linear energy transfer. While the dose, the dose rate, and dose distribution in tissue are aspects of a radiation exposure that can be varied experimentally or in medical treatments, the LET and eV are inherent characteristics of the type of radiation. High-LET radiation deposits a higher concentration of energy in a shorter distance when traversing tissue compared with low-LET radiation. The different biological effects of high and low LET with similar energies have been documented in vivo in animal models and in cultured cells. High-LET results in intense macromolecular damage and more cell death. Findings indicate that while both low- and high-LET radiation activate non-homologous end-joining DNA repair activity, efficient repair of high-LET radiation requires the homologous recombination repair pathway. Low- and high-LET radiation activate p53 transcription factor activity in most cells, but high LET activates NF-kB transcription factor at lower radiation doses than low-LET radiation. Here we review the development, uses, and current understanding of the cellular effects of low- and high-LET radiation exposure.

Biological and cellular responses of humans to high-level natural radiation: A clarion call for a fresh perspective on the linear no-threshold paradigm

There remains considerable uncertainty in obtaining risk estimates of adverse health outcomes of chronic low-dose radiation. In the absence of reliable direct data, extrapolation through the linear no-threshold (LNT) hypothesis forms the cardinal tenet of all risk assessments for low doses (≤ 100 mGy) and for the radiation protection principle of As Low As Reasonably Achievable (ALARA). However, as recent evidences demonstrate, LNT assumptions do not appropriately reflect the biology of the cell at the low-dose end of the dose-response curve. In this regard, human populations living in high-level natural radiation areas (HLNRA) of the world can provide valuable insights into the biological and cellular effects of chronic radiation to facilitate improved precision of the dose-response relationship at low doses. Here, data obtained over decades of epidemiological and radiobiological studies on HLNRA populations is summarized. These studies do not show any evidence of unfavourable health effects or adverse cellular effects that can be correlated with high-level natural radiation. Contrary to the assumptions of LNT, no excess cancer risks or untoward pregnancy outcomes have been found to be associated with cumulative radiation dose or in-utero exposures. Molecular biology-driven studies demonstrate that chronic low-dose activates several cellular defence mechanisms that help cells to sense, recover, survive, and adapt to radiation stress. These mechanisms include stress-response signaling, DNA repair, immune alterations and most importantly, the radiation-induced adaptive response. The HLNRA data is consistent with the new evolving paradigms of low-dose radiobiology and can help develop the theoretical framework of an alternate dose-response model. A rational integration of radiobiology with epidemiology data is imperative to reduce uncertainties in predicting the potential health risks of chronic low doses of radiation.

Cellular DNA effects of radiation and cancer risk assessment in cells with mitochondrial defects

Mitochondria play a key role in mediating non-targeted effects (NTE) post-radiation exposure. Mitochondrial DNA (mtDNA), due to its less efficient repair as compared to nuclear DNA, is more severely affected by radiation exposure and mutations in essential mtDNA genes can further exacerbate oxidative stress. Our objective was to evaluate the impact of mitochondrial defects on radiation-induced DDR and genomic instability, biomarkers that can foreshadow cancer development. To better understand this relationship, we used commercially available lymphoblastoid cell lines containing characterized mitochondrial mutations and studied the kinetics of DNA damage and relative telomere length (RTL) changes over time post 0.5 Gy X-ray exposure. Our work suggests that cells containing different mitochondrial mutations exhibit unique DNA damage and telomere length effects following radiation exposure. For example, a cell line containing a mitochondrial mutation in the ND4 subunit of complex 1 showed decreased growth rate, higher levels of persistent DNA damage, and telomere instability as compared to wild type. In contrast, a cell line with a mutation in the ATPase 6 mitochondrial protein showed more subtle negative alterations. These findings suggest mitochondrial integrity may play an important role in cellular changes that promote cancer. In total results indicate mitochondrial mutations can influence DNA damage kinetics and genomic instability and have long-term consequences in the ability to regain homeostasis following radiation exposure. These results may help explain, at least in part, the rationale for the persistent genomic instability often observed following a low dose of radiation and how it may promote cancer.

Protective Effect of QiOne® 2 Pro on Cultured Intestinal Epithelial Cells after Mobile Phone Radiation

QiOne® 2 Pro is a specific device which creates a static field that stimulates water molecules to undergo a transition into the coherent state. Since our body consists of about 70 to 85% of water (depending on age), this coherent state of the water molecules might increase the cellular resistance against exogenous reliabilities such as electromagnetic fields. In this study, the protective effect of QiOne® 2 Pro against mobile phone radiation was examined by using the cultured intestinal epithelial cells. Unprotected cells and untreated control cells served as point of reference. The cell regeneration process as well as the integrity of the intestinal epithelial barrier was investigated by measuring the transepithelial electrical resistance. Mobile phone radiation caused a reduced cell regenerative activity by approximately 60%, whereas the values were about 15% for QiOne® 2 Pro protected cells and untreated controls, respectively. Moreover, mobile phone radiation caused a rupture on the epithelial barrier in unprotected cells by cell death caused due to the oxidative stress with a complete loss of morphological integrity on the barrier. In contrast, untreated controls and QiOne® 2 Pro protected cells did not show any morphological change on the cell layers with an epithelial barrier of a 10-fold higher transepithelial electrical resistance than the unprotected cells. Overall the results clearly demonstrate the sensitivity of intestinal barrier against oxidative stress generated by mobile phone radiation. In addition, the results also show that the QiOne® 2 Pro device is able to reduce unwanted cellular effects of mobile phone radiation.

In Memoriam: Mortimer L. Mendelsohn: (1 December, 1925-8 January, 2020).

In Memoriam: Mortimer L. Mendelsohn: (1 December, 1925-8 January, 2020).

Fitting the Generalized Target Model to Cell Survival Data of Proton Radiation Reveals Dose-Dependent RBE and Inspires an Alternative Method to Estimate RBE in High-Dose Regions.

The imprecise estimation of the relative biological effectiveness (RBE) of proton radiation has been one of the main challenges for further calculating the biologically effective dose in proton therapy. Since dose levels can greatly influence the proton RBE, the relationship between the two should be clarified first. In addition, since the dose-response curves are usually too complex to readily assess RBE in high-dose regions, a reliable and simple method is needed to predict the RBE of proton radiation accurately in clinically relevant doses. The standard linear-quadratic (LQ) model is widely used to determine the RBE of particles for clinical applications. However, there has been some debate over its use when modeling the cell survival curves in high-dose regions, since those survival curves usually show linear behavior in the semilogarithmic plot. By considering both cellular repair effects and indirect effects of radiation, we have proposed a generalized target model with linear-quadratic linear (LQL) characteristics. For the more accurate evaluation of proton RBE in radiotherapy, here we used this generalized target model to fit the cell survival data in V79 and C3H 10T1/2 cells exposed to proton radiation with different LETs. The fitting results show that the generalized target model works as well as the LQ model in general. Based on the fitting parameters of the generalized target model, the RBE of six given doses DT (RBET) could be calculated in the corresponding cell lines with different LETs. The results show that the RBET gradually decreases with increased dose in both cell types. In addition, inspired by the calculation method of the maximum values of RBE (RBEM) in the low-dose region, a novel method was proposed for estimating the RBE in the high-dose region (RBEH) based on the slope ratio of the dose-response curves in this region. Linear regression analysis indicated a significant linear correlation between the proposed RBEH and the RBET in high-dose regions, which suggests that the current method can be used as an alternative tool, which is both simple and robust, to estimate RBE in high-dose regions.

Environmental Radio‐Toxins as Possible Radio‐biomarkers for Diseases of the CNS

A hypothesis is presented identifying environmental radon (EnRn) progeny as a radio‐biomarker of use in studies of the brain and central nervous system (CNS) diseases such as Alzheimer's (AD) and Parkinson's (PD). The long‐lived environmental radon progeny, Pb‐210/Po‐210, in air and soil is a common radio‐biomarker in plants and animals. Hydrocarbon combustion in power plants and internal combustion engines produce copious quantities of ultrafine carbon particles that entrain heavy metals such as Pb‐210 found in air of the combustion process. The UFP's laden with Pb‐210 are readily taken up in the lungs and transported by the blood throughout the body including the brain and CNS. The more numerous small UFP's (<10nm) can be transferred across the blood‐brain and cellular barriers into cells where Pb‐210 is permanently deposited. The Pb+2 ions can mimic Ca+2 in brain and CNS cellular action potential systems providing a pathway into the cells and producing deleterious biochemical effects, additionally with radioactive Pb‐210 there are cellular radiation effects. Within the context of the proposed hypothesis data of diseased brain tissues containing Pb‐210/Po‐210 showed selective deposition in the brain proteins in AD and brain lipids in PD, with increased Po‐210 in MS colon tissueSupport or Funding InformationThis abstract is an end result of over 40 years of collaborative studies of environment radon progeny in humans. Collaboration among scientists from academia, government and private industry is noted.The support programs are too numerous to mention, but have been recognized in peer‐reviewed publications associated with the work.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

THE COMPLEXITY OF QUANTITIES IN RADIATION DOSIMETRY: THE ISSUE OF RADIATION QUALITY.

When Harald Rossi developed a new radiation measurement instrument more than 60 years ago-the tissue equivalent low-pressure proportional counter, also called Rossi Counter-his initial intention was to provide a technique to measure LET. He realized soon that the measurements provided insight into the stochastic nature of the interactions of ionizing radiation with matter and that the measured results represented an alternative to characterize radiation quality in terms of stochastic or microdosimetric quantities. Progress in cellular and molecular radiation biology and in simulating charged particle tracks in biological entities are now essential features and have extended the original delineation of the field of microdosimetry. This general field of microdosimetry, as part of an interdisciplinary approach for the study of molecular mechanisms and cellular radiation effects, continues to be an important area of radiation research, documented by 13 previous Microdosimetry Symposia and, again, at this Symposium. However, the quantification of radiation quality remains a subject of practical importance. In fact, the issue has gained in importance due to the application of ions for therapy and due to the need for protection from exposures to complex and high-energy radiation fields, for example, to cosmic radiation in civil aviation and space missions. In practice pragmatic, empirical approaches are being used which has led to a complex set of dosimetric quantities and terms.

Accelerated senescence in skin in a murine model of radiation-induced multi-organ injury.

Accidental high-dose radiation exposures can lead to multi-organ injuries, including radiation dermatitis. The types of cellular damage leading to radiation dermatitis are not completely understood. To identify the cellular mechanisms that underlie radiation-induced skin injury in vivo, we evaluated the time-course of cellular effects of radiation (14, 16 or 17 Gy X-rays; 0.5 Gy/min) in the skin of C57BL/6 mice. Irradiation of 14 Gy induced mild inflammation, observed histologically, but no visible hair loss or erythema. However, 16 or 17 Gy radiation induced dry desquamation, erythema and mild ulceration, detectable within 14 days post-irradiation. Histological evaluation revealed inflammation with mast cell infiltration within 14days. Fibrosis occurred 80 days following 17 Gy irradiation, with collagen deposition, admixed with neutrophilic dermatitis, and necrotic debris. We found that in cultures of normal human keratinocytes, exposure to 17.9 Gy irradiation caused the upregulation of p21/waf1, a marker of senescence. Using western blot analysis of 17.9 Gy-irradiated mice skin samples, we also detected a marker of accelerated senescence (p21/waf1) 7 days post-irradiation, and a marker of cellular apoptosis (activated caspase-3) at 30 days, both preceding histological evidence of inflammatory infiltrates. Immunohistochemistry revealed reduced epithelial stem cells from hair follicles 14-30 days post-irradiation. Furthermore, p21/waf1 expression was increased in the region of the hair follicle stem cells at 14 days post 17 Gy irradiation. These data indicate that radiation induces accelerated cellular senescence in the region of the stem cell population of the skin.

Dedicated high dose rate 192Ir brachytherapy radiation fields for in vitro cell exposures at variable source-target cell distances: killing of mammalian cells depends on temporal dose rate fluctuation

Afterloading brachytherapy is conducted by the stepwise movement of a radioactive source through surgically implanted applicator tubes where at predefined dwell positions calculated dwell times optimize spatial dose delivery with respect to a planned dose level. The temporal exposure pattern exhibits drastic fluctuations in dose rate at a given coordinate and within a single treatment session because of the discontinuous and repeated source movement into the target volume. This could potentially affect biological response. Therefore, mammalian cells were exposed as monolayers to a high dose rate 192Ir source by utilizing a dedicated irradiation device where the distance between a planar array of radioactive source positions and the plane of the cell monolayer could be varied from 2.5 mm to 40 mm, thus varying dose rate pattern for any chosen total dose.The Gammamed IIi afterloading system equipped with a nominal 370 GBq (10 Ci) 192-Ir source was used to irradiate V79 Chinese hamster lung fibroblasts from both confluent and from exponential growth phase with dose up to 12 Gy (at room temperature, total exposure not exceeding 1 h). For comparison, V79 cells were also exposed to 6 MV x-rays from a clinical linear accelerator (dose rate of 2.5 Gy min−1). As biological endpoint, cell survival was determined by standard colony forming assay. Dose measurements were conducted with a diamond detector (sensitive area 7.3 mm2), calibrated by means of 60Co radiation. Additionally, dose delivery was simulated by Monte Carlo calculations using the EGSnrc code system. The calculated secondary electron fluence spectra at the cell location did not indicate a significant change of radiation quality (i.e. higher linear energy transfer) at the lower distances.Clonogenic cell survival curves obtained after brachytherapy exhibited an altered biological response compared to x-rays which was characterized by a significant reduction of the survival curve shoulder when dose rate fluctuations were high. Therefore, also for the time scale of the present investigation, cellular effects of radiation are not invariant to the temporal pattern in dose rate. We propose that with high dose rate variation the cells activate less efficiently their DNA damage response than after continuous irradiation.

Dynamic changes in the proteome of human peripheral blood mononuclear cells with low dose ionizing radiation

Humans are continually exposed to ionizing radiation from natural as well as anthropogenic sources. Though biological effects of high dose radiation exposures have been well accepted, studies on low-to-moderate dose exposures (in the range of 50–500mGy) have been strongly debated even as researchers continue to search for elusive ‘radiation signatures’ in humans. Proteins are considered as dynamic functional players that drive cellular responses. However, there is little proteomic information available in context of human exposure to ionizing radiation. In this study, we determined differential expressed proteins in G0 peripheral blood mononuclear cells (PBMCs) from healthy individuals 1h and 4h after ‘ex vivo’ exposure with two radiation doses (300mGy and 1Gy). Twenty-three proteins were found to be significantly altered in irradiated cells when compared to sham irradiated cells with fold change ±1.5-fold (p≤0.05), with only three proteins showing ≥2.5-fold change, either with dose or with time. Mass spectrometry analyses identified redox sensor protein, chloride intracellular channel protein 1 (CLIC-1), the antioxidant protein, peroxiredoxin-6 and the pro-survival molecular chaperone 78KDa glucose regulated protein (GRP78) among the 23 modulated proteins. The mean coefficient of variation (CV) for the twenty-three radiation responsive protein spots was found to be 33.7% for 300mGy and 48.3% for 1Gy. We thus, conclude that the radiation proteomic response of G0 human PBMCs, which are in the resting stage of the cell cycle, involves moderate upregulation of protective mechanisms, with low inter-individual variability. This study will help further our understanding of cellular effects of low dose acute radiation in humans and contribute toward differential biomarker discovery.

Cellular and molecular effects of electromagnetic radiation and sonic waves

Electromagnetic radiation (in the form of pulsed magnetic fields, radiofrequency and intense pulsed light) and mechanical agents (such as sonic waves) have been used in physical therapy. The aim of this study was to assess the effects of low-intensity magnetic fields, sonic and radiofrequency waves, and intense pulsed light on the survival of Escherichia coli cultures and on the electrophoretic mobility of plasmid DNA. Exponentially growing E. coli AB1157 cultures and plasmid DNA samples were exposed to these physical agents and 0.9% NaCl (negative control) and SnCl2 (positive control) solutions. Aliquots of the cultures were diluted and spread onto a solidified rich medium. The colony-forming units were counted after overnight incubation and the survival fraction was calculated. Agarose gel electrophoresis was performed to visualise and quantify the plasmid topological forms. The results suggest that these agents do not alter the survival of E. coli cells or plasmid DNA electrophoresis mobility. Moreover, they do not protect against the lesive action of SnCl2. These physical agents therefore had no cytotoxic or genotoxic effects under the conditions studied.

Pomegranate Supplementation Improves Affective and Motor Behavior in Mice after Radiation Exposure

Currently, NASA has plans for extended space travel, and previous research indicates that space radiation can have negative effects on cognitive skills as well as physical and mental health. With long-term space travel, astronauts will be exposed to greater radiation levels. Research shows that an antioxidant-enriched diet may offer some protection against the cellular effects of radiation and may provide significant neuroprotection from the effects of radiation-induced cognitive and behavioral skill deficits. Ninety-six C57BL/6 mice (48 pomegranate fed and 48 control) were irradiated with proton radiation (2 Gy), and two-month postradiation behaviors were assessed using a battery of behavioral tests to measure cognitive and motor functions. Proton irradiation was associated with depression-like behaviors in the tail suspension test, but this effect was ameliorated by the pomegranate diet. Males, in general, displayed worse coordination and balance than females on the rotarod task, and the pomegranate diet ameliorated this effect. Overall, it appears that proton irradiation, which may be encountered in space, may induce a different pattern of behavioral deficits in males than females and that a pomegranate diet may confer protection against some of those effects.

High-energy pulse-electron-beam-induced molecular and cellular damage in Saccharomyces cerevisiae

The high-energy pulse electron beam (HEPE) is a new method for mutation breeding. Previously, we demonstrated that HEPE radiation improved thermotolerance and ethanol production of Saccharomyces cerevisiae. To investigate the influence of HEPE on yeast molecular and cellular damage, cells were separately treated with HEPE radiation at different doses (0, 200, 400, 600, 800, 1000, 1200 and 1400 Gy). Based on results obtained, protein leakage and diffusion of intracellular nucleotide and propidium iodide (PI) uptake assays showed that HEPE clearly enhanced the cell membrane permeability of yeast depending on the dose of exposure. Yeast cells treated with HEPE radiation had significantly elevated levels of DNA instability, as detected by the chromosome spreading assay. These results correlated well with the measurement of increased levels of chromosomal aberrations and apoptosis. Intracellular reactive oxygen species (ROS) and caspase 3 activity were also measured in HEPE-applied yeast cells. Caspase 3 appeared to be involved in HEPE-induced apoptosis. Use of dihydroethidium staining and confocal laser scanning microscopy (CLSM) showed increased levels of intracellular ROS as a consequence of augmented pulsing. Moreover, yeast cells retained some photoreactivation capacity when the dose of HEPE exposure was less than 600 Gy. Thereafter, the level of damage was too serious to repair. Thus, photoreactivation had a repair effect upon HEPE radiation-induced damage. The results of our studies provide a possible explanation for the molecular and cellular effects of HEPE radiation upon S. cerevisiae.

Mutation induction by inhaled radon progeny modeled at the tissue level

The observable responses of living systems to ionizing radiation depend on the level of biological organization studied. Understanding the relationships between the responses characteristic of the different levels of organization is of crucial importance. The main objective of the present study is to investigate how some cellular effects of radiation manifest at the tissue level by modeling mutation induction due to chronic exposure to inhaled radon progeny. For this purpose, a mathematical model of the bronchial epithelium was elaborated to quantify cell nucleus hits and cell doses. Mutagenesis was modeled considering endogenous as well as radiation-induced DNA damages and cell cycle shortening due to cell inactivation. The model parameters describing the cellular effects of radiation are obtained from experimental data. Cell nucleus hits, cell doses, and mutation induction were computed for the activity hot spots of the large bronchi at different exposures. Results demonstrate that the mutagenic effect of densely ionizing radiation is dominated by cell cycle shortening due to cell inactivation and not by DNA damages. This suggests that radiation burdens of non-progenitor cells play a significant role in mutagenesis in case of protracted exposures to densely ionizing radiation. Mutation rate as a function of dose rate exhibits a convex shape below a threshold. This threshold indicates the exhaustion of the tissue regeneration capacity of local progenitor cells. It is suggested that progenitor cell hyperplasia occurs beyond the threshold dose rate, giving a possible explanation of the inverse dose-rate effect observed in the epidemiology of lung cancer among uranium miners.

The effect of non-targeted cellular mechanisms on lung cancer risk for chronic, low level radon exposures

Purpose: The goal of the present study was to investigate the effect of non-targeted mechanisms on the shape of the lung cancer risk function at chronic, low level radon exposures relative to direct cellular radiation effects. This includes detrimental and protective bystander effects, radio-adaptive bystander response, genomic instability and induction of apoptosis by surrounding cells.Methods: To quantify the dependence of these mechanisms on dose, analytical functions were derived from the experimental evidence presently available. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by a Transformation Frequency-Tissue Response (TF-TR) model, formulated in terms of cellular hits within the cycle time of the cell and then integrated over the whole exposure period.Results: In general, non-targeted effects like genomic instability and bystander effects amplify the biological effectiveness of a given radiation dose, while induction of apoptosis and adaptive response will decrease the risk values. While these observations are related to the absolute number of lung cancer cases, normalization to the epidemiologically observed risk at 0.675 Gy suggests that the effect of such mechanisms on the shape of the dose-response relationship may be different. Indeed, genomic instability and adaptive response cause a substantial reduction of the risk at low doses, while induction of apoptosis and detrimental bystander effects slightly increase the risk.Conclusions: Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates. However, the relatively large error bars of the epidemiological data do not currently allow the prediction of a statistically significant deviation from the Linear – No Threshold (LNT) assumption.

Non-thermal Cellular Effects of Low-power Microwave Radiation on the Lens and Lens Epithelial Cells

Because of the increased use of modern radiofrequency devices, public concern about the possible health effects of exposure to microwave radiation has arisen in many countries. It is well established that high-power microwave radiation can induce cataracts via its thermal effects. It remains unclear whether low-power microwave radiation, especially at levels below the current exposure limits, is cataractogenic. This review summarizes studies on the biological effects of low-power microwave radiation on lens and lens epithelial cells (LECs). It has been reported that exposure affects lens transparency, alters cell proliferation and apoptosis, inhibits gap junctional intercellular communication, and induces genetic instability and stress responses in LECs. These results raise the question of whether the ambient microwave environment can induce non-thermal effects in the lens and whether such effects have potential health consequences. Further in vivo studies on the effects on the lens of exposure to low-power microwave radiation are needed.

Peculiar low-radiation effects as a risk factor: assessment of organism viability in model experiments with Daphnia magna

In model experiments on the crayfish Daphnia magna Straus, the importance of peculiar disturbing cellular effects of low radiation was studied. We showed that even at a dose of 0.1 Gy, which is a thousand times lower than predicted as lethal (100 Gy), the probability of the animals' death increases. The process was registered for the greater part of Daphnia's lifetime. The frequency of death of irradiated animals did not increase with doses increasing from 1 to 20 Gy. Because cellular dose-independent effects were found on the subjects of various species (including rats), we decided that these effects may affect the viability of mammals even at low doses of radiation.

Molecular and Cellular Late Radiation Effects in Generations of CHO Line Cells

Changes in the genome damage level, radiosensitivity and apoptotic cells number were studied in different generations of irradiated Chinese Hamster Ovary cells (CHO K1 cell line). Three independent experiments were conducted. Using the neutral version (neutral pH) of DNA comet assay we registered 1.5-2.0 folds increase in DNA fragmentation (mainly due to double-strand DNA breaks) in cells immediately after gamma-rays irradiation in dose of 1 Gy. The DNA fragmentation level in generations of irradiated cells 2-4 days after exposure was similar to control values. However, the significant increase of DNA fragmentation (de novo) was registered 7 days after exposure to gamma-radiation that is probably appearance of the radiation-induced genome instability. The increase of DNA fragmentation remains up to 21st day of experiments with maximum values for 11th and 18th days. Nevertheless, the DNA fragmentation level in generations of irradiated cells for 23-28 days after exposure was reduced to control values. The results on the apoptotic cells level using “DNA-halo” method showed significant increase of the apoptotic cells fraction in generations of irradiated cells for 7-21st days after exposure. Most probably, the increase of DNA fragmentation level described above is conditioned by significant level of apoptotic cells with high-fragmented DNA. The most interesting results were obtained after investigations of the irradiated cells generations radiosensitivity. Thus, the significant increase of cells sensitivity to additional gamma-rays irradiation in dose of 10 Gy was shown for 9, 11, 16 and 18th days after exposure but there was an converse effect (resistant to additional irradiation) since 21st day up to the end of experiments (28th day). In conclusion, the obtained results are recent and demonstrate a selective pressure of the genome instability leading to the radioresistant cell clones forming. Grant support: RFBR grant #07-04-01009a.