Low Dose Rate Irradiation Research Articles

Diminished or inversed dose-rate effect on clonogenic ability in Ku-deficient rodent cells.

The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced. This phenomenon is known as ‘the dose-rate effect’. The dose-rate effect is considered to be due to the repair of DNA damage during irradiation but the precise mechanisms for the dose-rate effect remain to be clarified. Ku70, Ku86 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are thought to comprise the sensor for DNA double-strand break (DSB) repair through non-homologous end joining (NHEJ). In this study, we measured the clonogenic ability of Ku70-, Ku86- or DNA-PKcs-deficient rodent cells, in parallel with respective control cells, in response to high dose-rate (HDR) and low dose-rate (LDR) γ-ray radiation (~0.9 and ~1 mGy/min, respectively). Control cells and murine embryonic fibroblasts (MEF) from a severe combined immunodeficiency (scid) mouse, which is DNA-PKcs-deficient, showed higher cell survival after LDR irradiation than after HDR irradiation at the same dose. On the other hand, MEF from Ku70−/− mice exhibited lower clonogenic cell survival after LDR irradiation than after HDR irradiation. XR-V15B and xrs-5 cells, which are Ku86-deficient, exhibited mostly identical clonogenic cell survival after LDR and HDR irradiation. Thus, the dose-rate effect in terms of clonogenic cell survival is diminished or even inversed in Ku-deficient rodent cells. These observations indicate the involvement of Ku in the dose-rate effect.

Effects of Continuous In Utero Low- and Medium-Dose-Rate Gamma-Ray Exposure on Fetal Germ Cells.

The effects of radiation exposure on germ cells and the gonads have been well studied at acute high-dose exposures, but the effects of chronic low-dose-rate (LDR) irradiation, particularly relevant for radiation protection, on germ cells and the gonads are largely unknown. Our previous study revealed that chronic exposure of mice to medium-dose-rate (MDR, 200 or 400 mGy/day) gamma-rays in utero for the entire gestation period (18 days) induced only a mild degree of general growth retardation, but with very drastic effects on the gonads and germ cells. In the current study, we further investigated the histomorphological changes in the gonads and the number of germ cells from gestation day (GD) 18 fetuses irradiated with MDR throughout the entire gestation period. The germ cells in the testes and ovaries of the MDR-irradiated fetuses were almost obliterated. Gestation day 18 fetuses exposed to LDR (20 mGy/day) radiation for the entire gestation period showed decreases in the number of the germ cells, which were not statistically significant or only marginally significant at most. Further investigations on the effects of LDR irradiation in utero using more sensitive methods are necessary.

VADER: a variable dose-rate external 137Cs irradiator for internal emitter and low dose rate studies

In the long term, 137Cs is probably the most biologically important agent released in many accidental (or malicious) radiation disasters. It can enter the food chain, and be consumed, or, if present in the environment (e.g. from fallout), can provide external irradiation over prolonged times. In either case, due to the high penetration of the energetic γ rays emitted by 137Cs, the individual will be exposed to a low dose rate, uniform, whole body, irradiation. The VADER (VAriable Dose-rate External 137Cs irradiatoR) allows modeling these exposures, bypassing many of the problems inherent in internal emitter studies. Making use of discarded 137Cs brachytherapy seeds, the VADER can provide varying low dose rate irradiations at dose rates of 0.1 to 1.2 Gy/day. The VADER includes a mouse “hotel”, designed to allow long term simultaneous residency of up to 15 mice. Two source platters containing ~ 250 mCi each of 137Cs brachytherapy seeds are mounted above and below the “hotel” and can be moved under computer control to provide constant low dose rate or a varying dose rate mimicking 137Cs biokinetics in mouse or man. We present the VADER design and characterization of its performance over 18 months of use.

ITRAQ-Based Proteomic Profiling of Potential Biomarkers in Rat Serum for Uranium Tailing Suspension Intratracheal Instillation.

Protection against low-dose ionizing radiation is of great significance. Uranium tailings are formed as a byproduct of uranium mining and a potential risk to organisms. In this study, we identified potential biomarkers associated with exposure to low-dose radiation from uranium tailings. We established a Wistar rat model of low dose rate irradiation by intratracheal instillation of a uranium tailing suspension. We observed pathological changes in the liver, lung, and kidney tissues of the rats. Using isobaric tags for relative and absolute quantification, we screened 17 common differentially expressed proteins in three dose groups. We chose alpha-1 antiproteinase (Serpina1), keratin 17 (Krt17), and aldehyde dehydrogenase (Aldh3a1) for further investigation. Our data showed that expression of Serpina1, Krt17, and Aldh3a1 had changed after the intratracheal instillation in rats, which may be potential biomarkers for uranium tailing low-dose irradiation. However, the underlying mechanisms require further investigation.

A modified accelerated testing method of ELDRS in extreme-low dose rate irradiation

Low dose rate radiation induced gain degradation in bipolar devices is considered to be the primary threat to the spacecraft reliability and service life. In order to examine the radiation tolerance of bipolar devices, it is recommended to use 10 m rad(Si)/s as the typical dose rate in the standards MIL-STD-883G. There is lack of solid study to prove the dose rate is sufficient enough low. Our latest experiment results showed that the enhanced low dose rate sensitivity (ELDRS) effects was not saturated at 10 m rad(Si)/s. To examine the reliability of bipolar devices in extreme low dose rate environment below 10 m rad(Si)/s in short time, we proposed a modified accelerated testing method of ELDRS effects in extreme-low dose rate irradiation based on elevated temperature irradiation and temperature-switching during irradiation, which is helpful to get quantified results in the whole low dose rate range.

Temperature dependence of bipolar junction transistor current-voltage characteristics after low dose rate irradiation

Temperature variation on board can have a significant impact on electronic circuit parameters. In this paper, we investigate and model how both irradiated NPN and PNP-Bipolar Junction Transistors (BJTs) at room temperature respond electrically to temperature variation. A temperature-dependent analytical model for total-ionizing-dose-induced excess base current in BJTs is proposed. Our model captures base current dependence on temperature on irradiated parts. To do so, the devices under test are irradiated at room temperature with all terminals grounded. After irradiation, base currents are obtained, and the concentrations of oxide defects (i.e., oxide trapped charge and interface traps) created during irradiation are calculated. At the end, results from our analytical model and experimental data are compared to SPICE simulations. Both base current and defect densities resulting from room temperature irradiations are used as inputs to SPICE simulations and the analytical model. Experimental data obtained from measurements at both low and high temperatures on parts irradiated at room temperature are shown to compare well to the simulation results and analytical model over a range of temperatures. The modeling work shows that SPICE simulations can support qualification for commercial-off-the-shelf (COTS) linear bipolar components with temperature for space applications.

A unique high natural background radiation area – Dose assessment and perspectives

The biological effects of low dose-rate radiation exposures on humans remains unknown. In fact, the Japanese nation still struggles with this issue after the Fukushima Dai-ichi Nuclear Power Plant accident. Recently, we have found a unique area in Indonesia where naturally high radiation levels are present, resulting in chronic low dose-rate radiation exposures. We aimed to estimate the comprehensive dose due to internal and external exposures at the particularly high natural radiation area, and to discuss the enhancement mechanism of radon. A car-borne survey was conducted to estimate the external doses from terrestrial radiation. Indoor radon measurements were made in 47 dwellings over three to five months, covering the two typical seasons, to estimate the internal doses. Atmospheric radon gases were simultaneously collected at several heights to evaluate the vertical distribution. The absorbed dose rates in air in the study area vary widely between 50 nGy h−1 and 1109 nGy h−1. Indoor radon concentrations ranged from 124 Bq m−3 to 1015 Bq m−3. That is, the indoor radon concentrations measured exceed the reference levels of 100 Bq m−3 recommended by the World Health Organization. Furthermore, the outdoor radon concentrations measured were comparable to the high indoor radon concentrations. The annual effective dose due to external and internal exposures in the study area was estimated to be 27 mSv using the median values. It was found that many residents are receiving radiation exposure from natural radionuclides over the dose limit for occupational exposure to radiation workers. This enhanced outdoor radon concentration might be as a result of the stable atmospheric conditions generated at an exceptionally low altitude. Our findings suggest that this area provides a unique opportunity to conduct an epidemiological study related to health effects due to chronic low dose-rate radiation exposure.

Environmental radiation on large Japanese field mice in Fukushima reduced colony forming potential in hematopoietic progenitor cells without inducing genomic instability

Purpose To study the environmental radiation effects of wild animals after the Fukushima Dai-ichi nuclear power plant accident, we assessed effects on hematopoietic progenitor cells (HPCs) in large Japanese field mice (Apodemus speciosus). Materials and methods A. speciosus were collected from three contaminated sites and control area. The air dose-rates at the control and contaminated areas were 0.96 ± 0.05 μGy/d (Hirosaki), 14.4 ± 2.4 μGy/d (Tanashio), 208.8 ± 31.2 μGy/d (Ide), 470.4 ± 93.6 μGy/d (Omaru), respectively. We investigated possible DNA damage and pro-inflammatory markers in the bone marrow (BM) cells. The colony-forming potential of BM cells was estimated by the number of HPC colony-forming cells. Radiation-induced genomic instability (RIGI) in HPCs was also analyzed by quantifying delayed DNA damage in CFU-GM clones. Results Although no significant differences in DNA damage and inflammation markers in BM cells from control and contaminated areas, the number of HPC colonies exhibited an inverse correlation with air dose-rate. With regard to RIGI, no significant differences in DNA damage of CFU-GM clones between the mice from the control and the three contaminated areas. Conclusions Our study suggests that low dose-rate radiation of more than 200 Gy/d reduced HPCs, possibly eliminating genomically unstable HPCs.

Association between low doses of ionizing radiation, administered acutely or chronically, and time to onset of stroke in a rat model.

Exposure to high-doses of ionizing radiation has been reported to be associated with the risk of stroke. However, risks associated with lower dose exposures remain unclear, and there is little information available for the risk modification according to the dose-rate. There are few studies using animal models which might be able to provide complementary information on this association. In this study, the male stroke-prone spontaneously hypertensive rat (SHRSP) was used as a model animal. The rats were acutely irradiated with doses between 0 and 1.0 Gy or chronically irradiated with a cumulative dose of 0.5 or 1.0 Gy (at a dose rate of 0.05 or 0.1 Gy/day, respectively). The onset time of stroke related symptoms in SHRSP was used as an endpoint for evaluating the effects of low dose and the low dose-rate gamma-ray exposures. With respect to acute exposure, the time to the onset of stroke in the irradiated rats suggested the presence of a threshold around 0.1 Gy. For the low dose-rate chronically exposed, no significant increase in stroke symptom was observed. These findings are novel and demonstrate that the SHRSP system can be used to determine the association between the risk of stroke and radiation exposure with high sensitivity. Moreover, these studies provide important information regarding the association between the low dose and low dose-rate radiation exposure and circulatory diseases, especially stroke.

Pelvic Reirradiation Utilizing Pulsed Low-dose Rate Radiation Therapy.

Pulsed low-dose rate radiation therapy has been shown to reduce normal tissue damage while decreasing DNA damage repair in tumor cells. In a cohort of patients treated with palliative or definitive pelvic reirradiation using pulsed low-dose rate radiation therapy, we observed substantial local control and low rates of toxicity.

Assessment of chromosome aberrations in large Japanese field mice (Apodemus speciosus) in Namie Town, Fukushima

Purpose After the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in Japan on March 11 2011, the surroundings became contaminated with radionuclides. To understand the possible biological effects after chronic low dose-rate radiation in contaminated areas of Fukushima, we assessed the effects in large Japanese field mice (Apodemus speciosus) by means of chromosome aberration analysis. Materials and methods We collected A. speciosus in five sites around Namie Town, Fukushima (contaminated areas) and in two sites in Hirosaki City, Aomori (control areas, 350 km north of FDNPP) from autumn 2011 to 2013. The number of mice captured and ambient dose-rates were as follows: high (n = 11, 10.1–30.0 µGy h−1), moderate (n = 10, 5.7–15.6 µGy h−1), low (n = 12, 0.23–1.14 µGy h−1) and control (n = 20, 0.04–0.07 µGy h−1). After spleen extraction from rodents, spleen cell culture was performed to obtain metaphase spreads. Chromosome aberrations were assessed on Giemsa-stained metaphase spreads. Results Although the mice in the contaminated areas were chronically exposed, there was no radiation-specific chromosome aberrations observed, such as dicentric chromosomes and rings. Some structural aberrations such as gaps and breaks were observed, and these frequencies decreased annually in mice from Namie Town. Conclusion These findings suggest that chromosome aberration analysis is useful to evaluate and monitor radiation effects in wild animals.

Field Study of the Possible Effect of Parental Irradiation on the Germline of Children Born to Cleanup Workers and Evacuees of the Chornobyl Nuclear Accident.

Although transgenerational effects of exposure to ionizing radiation have long been a concern, human research to date has been confined to studies of disease phenotypes in groups exposed to high doses and high dose rates, such as the Japanese atomic bomb survivors. Transgenerational effects of parental irradiation can be addressed using powerful new genomic technologies. In collaboration with the Ukrainian National Research Center for Radiation Medicine, the US National Cancer Institute, in 2014-2018, initiated a genomic alterations study among children born in selected regions of Ukraine to cleanup workers and/or evacuees exposed to low-dose-rate radiation after the 1986 Chornobyl (Chernobyl) nuclear accident. To investigate whether parental radiation exposure is associated with germline mutations and genomic alterations in the offspring, we are collecting biospecimens from father-mother-offspring constellations to study de novo mutations, minisatellite mutations, copy-number changes, structural variants, genomic insertions and deletions, methylation profiles, and telomere length. Genomic alterations are being examined in relation to parental gonadal dose, reconstructed using questionnaire and measurement data. Subjects are being recruited in exposure categories that will allow examination of parental origin, duration, and timing of exposure in relation to conception. Here we describe the study methodology and recruitment results and provide descriptive information on the first 150 families (mother-father-child(ren)) enrolled.

The Double Threshold: Consequences for Identifying Low-Dose Radiation Effects.

Prior to observing low-dose-induced cell signaling and adaptive protection, radiogenic stochastic effects were assumed to be linearly related to absorbed dose. Now, abundant data prove the occurrence of radiogenic adaptive protection specifically at doses below ∼ 200 mGy (with some data suggesting such protection at a dose even higher than 200 mGy). Moreover, cells do not thrive properly when deprived of radiation below background dose.Two threshold doses need be considered in constructing a valid dose-response relationship. With doses beginning to rise from zero, cells increasingly escape radiation deprivation. The dose at which radiation-deprived cells begin to function homeostatically provides dose Threshold A. With further dose increase, adaptive protection becomes prominent and then largely disappears at acute doses above ∼ 200 mGy. The dose at which damage begins to override protection defines Threshold B.Thresholds A and B should be terms in modeling dose-response functions. Regarding whole-body responses, current data suggest for low-LET acute, non-chronic, irradiation a Threshold B of about 100 mGy prevails, except for leukemia and probably some other malignancies, and for chronic, low dose-rate irradiation where the Threshold B may well reach 1 Gy per year. A new Research and Development Program should determine individual Thresholds A and B for various radiogenic cell responses depending on radiation quality and target.

Long term variations of galactic cosmic radiation on board the International Space Station, on the Moon and on the surface of Mars

<div class="abstract"> <p> <div><div class="abstract"> <div><p>The radiation environment in free space and the related radiation exposure is seen as one of the main health detriments for future long-duration human exploration missions beyond Low Earth Orbit (LEO). The steady flux of energetic particles in the galactic cosmic radiation (GCR) produces  a low dose-rate radiation exposure, which is heavily influenced by several factors including the solar cycle, the presence of an atmosphere, relevant magnetic fields (as on Earth) and of course by the relevant spacecraft shielding. Investigations of the GCR variations over the course of a solar cycle provide valuable data for exploration mission planning and for the determination of the radiation load received due to the GCR environment. Within the current work these investigations have been performed applying three datasets generated on board the International Space Station (ISS) with the DOSTEL instruments in the frame of the DOSIS and DOSIS-3D projects, with the CRaTER instrument in a Moon orbit and with the MSL-RAD instrument on the way to and on the surface of Mars. To derive GCR dose contributions on board the ISS two procedures have been developed separating the contributions from GCR from passing’s through the South Atlantic Anomaly (SAA), as well as ways to extrapolate the GCR dose measured on board the ISS to free space based on various ranges of the McIlwain <em>L</em>-shell parameter. At the end we provide a dataset spanning the timeframe for GCR measurements on the ISS (2009 – 2011 & 2012 – 2019), Moon (2009 – 2019) and Mars (2012 – 2019), thereby covering the time span from the deep minimum of solar cycle 23, the ascending phase and maximum of solar cycle 24, and the descending phase of cycle 24, which is ongoing at the time of this writing.</p> </div> </div></div> </p> </div>

Hepatic effects of low-dose rate radiation in natural mouse populations (Apodemus uralensis and Apodemus agrarius): comparative interspecific analysis

Hypothesis: Natural mouse populations in radioactive contamination zone provide adequate information about dose loads and biological effects for ‘non-human biota’. The comparative analysis of the responses of different species of mice allows us to reveal the possible variation in the effects of low-dose rate radiation relative to the ecological-physiological and functional-metabolic features of the species.Materials and methods: Objects of study – two sympatric rodent species [pygmy wood mouse (Apodemus uralensis Pallas, 1811) and striped field mouse (Apodemus agrarius Pallas, 1771)] caught on the territory of the East-Ural radioactive trace (EURT). The EURT zone is consequence the Kyshtym accident in South Urals in 1957. Nowadays, the main dose-forming radionuclide is β-emitting 90Sr. The individual dose rate of impacted mice caused by internal exposure to 90Sr varied from 0.021 to 0.152 mGy/day. The baseline functional-metabolic characteristics of the liver were researched: protein-, lipid-, and glycogen-synthesizing processes; glycolysis; aerobic synthesis of ATP; lipid peroxidation; and the H2O2-scavenging enzymatic status; and the functional activity of the genome.Results: The hepatic shifts for impacted populations are amplified with increasing dose rate of irradiation, regardless of which species is considered. But, the response of closely related species of rodents to irradiation is different both in the vector and the level (in A. agrarius sample was 2 time higher than that for A. uralensis).Conclusion: The radiation-induced hepatic shifts in A. uralensis from the EURT area correspond to the chronic response under stressful environmental conditions. The impacted population of A. agrarius can be considered the more reactive species to the radiation burden, demonstrating an acute effect. The interspecies contrast in the radiation response is associated with the original interspecies differences (background rodents’ samples in 28 km from the impact study site), and also the degree of residency of the species in the impact plots.

Plants in the Light of Ionizing Radiation: What Have We Learned From Chernobyl, Fukushima, and Other "Hot" Places?

Perhaps the main factor determining success of space travel will be the ability to control effects of ionizing radiation for humans, but also for other living organisms. Manned space travel will require the cultivation of food plants under conditions of prolonged exposure to ionizing radiation. Although there is a significant literature concerning the effects of acute high dose rate exposures on plant genetics, growth, and development, much less is known concerning the effects of chronic low dose irradiation especially those related to the impacts of the high energy protons and heavy ions that are encountered in the space environment. Here, we make the argument that in situ studies of the effects of radionuclides at nuclear accident sites (e.g., Chernobyl and Fukushima), atomic bomb test sites, and areas of naturally high radiation levels, could provide insights concerning the mechanisms of radiation effects on living systems that cannot be assessed short of conducting research in space, which is not yet feasible for large scale, long term, multigenerational experiments. In this article we review the literature concerning the effects of chronic low-dose rate radiation exposure from studies conducted in Chernobyl, Fukushima, and other regions of the world with high ambient radiation levels (parts of India in particular). In general, mutation rates and other measures of genetic damage are considerably elevated, pollen and seed viability are reduced, growth rates are slower, and the frequency of developmental abnormalities is increased, although there is considerable variation among taxa for these effects. In addition, there are interactions between radiation and other environmental stressors (e.g., temperature, drought, heavy metals) that may play important roles in determining susceptibility to radiation induced stress.

Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity.

BackgroundManagement of locoregionally recurrent head and neck squamous cell carcinomas (HNSCC) is challenging due to potential radioresistance. Pulsed low-dose rate (PLDR) irradiation exploits phenomena of increased radiosensitivity, low-dose hyperradiosensitivity (LDHRS), and inverse dose-rate effect. The purpose of this study was to evaluate LDHRS and the effect of PLDR irradiation in isogenic HNSCC cells with different radiosensitivity.Materials and methodsCell survival after different irradiation regimens in isogenic parental FaDu and radioresistant FaDu-RR cells was determined by clonogenic assay; post irradiation cell cycle distribution was studied by flow cytometry; the expression of DNA damage signalling genes was assesed by reverse transcription-quantitative PCR.ResultsRadioresistant Fadu-RR cells displayed LDHRS and were more sensitive to PLDR irradiation than parental FaDu cells. In both cell lines, cell cycle was arrested in G2/M phase 5 hours after irradiation. It was restored 24 hours after irradiation in parental, but not in the radioresistant cells, which were arrested in G1-phase. DNA damage signalling genes were under-expressed in radioresistant compared to parental cells. Irradiation increased DNA damage signalling gene expression in radioresistant cells, while in parental cells only few genes were under-expressed.ConclusionsWe demonstrated LDHRS in isogenic radioresistant cells, but not in the parental cells. Survival of LDHRS-positive radioresistant cells after PLDR was significantly reduced. This reduction in cell survival is associated with variations in DNA damage signalling gene expression observed in response to PLDR most likely through different regulation of cell cycle checkpoints.

EVALUATION OF THE FATTY ACID DESATURASE 3 GENES STABILITY IN FLAX SEEDS HARVESTED FROM RADIO-CONTAMINATED AREA NEAR CHERNOBYL

Environment around Chernobyl recoveres from nuclear accident in 1986 and provides a base for plant adaptation research. Here, the initial platform was established for molecular screening of flax genome affected by radioactive contamination. Flax (Linum usitatissimum L.) cultivated in the radio-contaminated, and remediated experimental field near Chernobyl was investigated. Specifically, two gene isoforms of FAD3 gene, FAD3A and FAD3B, were evaluated using the restriction analysis, and direct sequencing. The aim of the presented study was to identify mutations, and single nucleotide polymorphisms within the FAD3A and FAD3B genes. The investigation was performed more than 25 years after Chernobyl accident. Therefore, the effect of chronic low dose rate irradiation on flax plants was considered.

Sensitivity analysis of parameters and methodological choices used in calculation of radiation detriment for solid cancer

Purpose: Radiation detriment is a concept used by the International Commission on Radiological Protection (ICRP) to quantify the harmful health effects of radiation exposure in humans. The current approach of radiation detriment calculation has been defined in ICRP Publication 103 in 2007. It is determined from lifetime risk of cancer and heritable effects for a composite reference population, taking into account the severity of the disease in terms of lethality, quality of life and years of life lost. Many parameters are used in the calculations and the variation of these parameters can have effects on the cancer detriment, which needs to be investigated.Materials and methods: In this paper, we conducted a sensitivity analysis for examining the impact of 12 different parameters or methodological choices on the calculation of solid cancer detriment, such as the lifetime risk calculation method, survival curve, dose and dose-rate effectiveness factor (DDREF), age-at-exposure, sex, reference population, risk transfer model, latency, attained age, lethality, minimum quality of life factor and relative cancer-free life lost. Sensitivity calculations have been performed systematically for each of 10 solid cancer sites, by changing each one of the parameters in turn.Results: This sensitivity analysis demonstrated a large impact on estimated detriment from DDREF, age-at-exposure, sex and lethality, a noticeable impact of risk transfer model associated to variation of baseline rates, and a limited impact of risk calculation method, survival curve, latency, attained age, quality of life and relative years of life lost.Conclusion: These results could have implications for radiation protection standards, and they should help define priorities for future research in the field of low radiation dose and dose rate research. The present sensitivity analysis is part of a global effort of ICRP to review the bases of radiation detriment calculation and assess potential evolutions to improve the radiation protection system.

DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure.

Environmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident or improvised nuclear device, and highlights the need to develop biological assays for low-dose rate, internal emitter radiation. To mimic low-dose rates attributable to fallout, we have developed a VAriable Dose-rate External 137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low-dose rate irradiations in the range of 0.1-1.2Gy/day, while circumventing the complexities of dealing with radioactively contaminated biomaterials. We investigated the kinetics of mouse peripheral leukocytes DNA damage response in vivo after variable, low-dose rate 137Cs exposure. C57BL/6 mice were placed in the VADER over 7days with total accumulated dose up to 2.7Gy. Peripheral blood response including the leukocyte depletion, apoptosis as well as its signal protein p53 and DNA repair biomarker γ-H2AX was measured. The results illustrated that blood leukocyte numbers had significantly dropped by day 7. P53 levels peaked at day 2 (total dose = 0.91Gy) and then declined; whereas, γ-H2AX fluorescence intensity (MFI) and foci number generally increased with accumulated dose and peaked at day 5 (total dose = 2.08Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2Gy and ≥ 2Gy, highlighting the potential of γ-H2AX MFI as a biomarker fordosimetry in a protracted, environmental exposure scenario.