Showing papers by "Chalk River Laboratories published in 2015"

From soft harmonic phonons to fast relaxational dynamics in CH 3 NH 3 PbBr 3

Abstract: The lead-halide perovskites, including ${\mathrm{CH}}_{3}{\mathrm{NH}}_{3}{\mathrm{PbBr}}_{3}$, are components in cost effective, highly efficient photovoltaics, where the interactions of the molecular cations with the inorganic framework are suggested to influence the electronic and ferroelectric properties. ${\mathrm{CH}}_{3}{\mathrm{NH}}_{3}{\mathrm{PbBr}}_{3}$ undergoes a series of structural transitions associated with orientational order of the ${\mathrm{CH}}_{3}{\mathrm{NH}}_{3}$ (methylammonium) molecular cation and tilting of the ${\mathrm{PbBr}}_{3}$ host framework. We apply high-resolution neutron scattering to study the soft harmonic phonons associated with these transitions, and find a strong coupling between the ${\mathrm{PbBr}}_{3}$ framework and the quasistatic ${\mathrm{CH}}_{3}{\mathrm{NH}}_{3}$ dynamics at low energy transfers. At higher energy transfers, we observe a ${\mathrm{PbBr}}_{6}$ octahedra soft mode driving a transition at 150 K from bound molecular excitations at low temperatures to relatively fast relaxational excitations that extend up to $\ensuremath{\sim}50\text{--}100$ meV. We suggest that these temporally overdamped dynamics enables possible indirect band gap processes in these materials that are related to the enhanced photovoltaic properties.

Molecular structures of fluid phosphatidylethanolamine bilayers obtained from simulation-to-experiment comparisons and experimental scattering density profiles.

Abstract: Following our previous efforts in determining the structures of commonly used PC, PG, and PS bilayers, we continue our studies of fully hydrated, fluid phase PE bilayers. The newly designed parsing scheme for PE bilayers was based on extensive MD simulations, and is utilized in the SDP analysis of both X-ray and neutron (contrast varied) scattering measurements. Obtained experimental scattering form factors are directly compared to our simulation results, and can serve as a benchmark for future developed force fields. Among the evaluated structural parameters, namely, area per lipid A, overall bilayer thickness DB, and hydrocarbon region thickness 2DC, the PE bilayer response to changing temperature is similar to previously studied bilayers with different headgroups. On the other hand, the reduced hydration of PE headgroups, as well as the strong hydrogen bonding between PE headgroups, dramatically affects lateral packing within the bilayer. Despite sharing the same glycerol backbone, a markedly smaller a...

Frustrated fcc antiferromagnet Ba 2 YOsO 6 : Structural characterization, magnetic properties, and neutron scattering studies

Abstract: We report the crystal structure, magnetization, and neutron scattering measurements on the double perovskite ${\mathrm{Ba}}_{2}{\mathrm{YOsO}}_{6}$. The $Fm\overline{3}m$ space group is found both at 290 K and 3.5 K with cell constants ${a}_{0}=8.3541(4)$ \AA{} and $8.3435(4)$ \AA{}, respectively. ${\mathrm{Os}}^{5+} (5{d}^{3})$ ions occupy a nondistorted, geometrically frustrated face-centered-cubic (fcc) lattice. A Curie-Weiss temperature $\ensuremath{\theta}\ensuremath{\sim}\ensuremath{-}700$ K suggests the presence of a large antiferromagnetic interaction and a high degree of magnetic frustration. A magnetic transition to long-range antiferromagnetic order, consistent with a type-I fcc state below ${T}_{\mathrm{N}}\ensuremath{\sim}69$ K, is revealed by magnetization, Fisher heat capacity, and elastic neutron scattering, with an ordered moment of 1.65(6) ${\ensuremath{\mu}}_{B}$ on ${\mathrm{Os}}^{5+}$. The ordered moment is much reduced from either the expected spin-only value of $\ensuremath{\sim}3 {\ensuremath{\mu}}_{B}$ or the value appropriate to $4{d}^{3} {\mathrm{Ru}}^{5+}$ in isostructural ${\mathrm{Ba}}_{2}{\mathrm{YRuO}}_{6}$ of 2.2(1) ${\ensuremath{\mu}}_{B}$, suggesting a role for spin-orbit coupling (SOC). Triple-axis neutron scattering measurements of the order parameter suggest an additional first-order transition at $T=67.45$ K, and the existence of a second-ordered state. Time-of-flight inelastic neutron results reveal a large spin gap $\ensuremath{\Delta}\ensuremath{\sim}17$ meV, unexpected for an orbitally quenched, ${d}^{3}$ electronic configuration. We discuss this in the context of the $\ensuremath{\sim}5$ meV spin gap observed in the related ${\mathrm{Ru}}^{5+},\phantom{\rule{0.16em}{0ex}}4{d}^{3}$ cubic double perovskite ${\mathrm{Ba}}_{2}{\mathrm{YRuO}}_{6}$, and attribute the $\ensuremath{\sim}3$ times larger gap to stronger SOC present in this heavier, $5d$, osmate system.

Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization.

Abstract: While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments and the high costs associated with protection from the deleterious physiological effects of exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the foundations of a roadmap toward enhancing human radioresistance for the purposes of deep space colonization and exploration. We outline future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, and methods of slowing metabolic activity while preserving cognitive function. We conclude by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well.

Improving microstructure and ductility in the Mg–Zn alloy system by combinational Ce–Ca microalloying

Abstract: A strategy is proposed to enhance the microstructure and mechanical properties of Mg–Zn alloys by combining microalloying additions of the rare earth element Ce and the non-rare earth element Ca. The double additions of Ce–Ca are found to significantly increase tensile elongation compared to binary Mg–Zn, or single additions of either Ce or Ca. Microstructure analysis reveals that the Ce–Ca additions increase ductility by modifying texture and refining grain size. Texture modification is attributed to solute effects from the microalloying elements, particularly Ca, while grain refinement is additionally influenced by a fine dispersion of Mg6Ca2Zn3 precipitates that form during rolling and pin grain boundaries. The microalloying element additions also lead to large secondary phase particles in the alloys, which can limit ductility enhancement by promoting early fracture. By scaling Zn content in the Mg–Zn–Ce–Ca alloys, the Mg6Ca2Zn3 phase fraction and Zn solute content can be controlled for optimum ductility or strengthening potential.

Structural and Magnetic Phase Transitions near Optimal Superconductivity in BaFe 2 ( As 1 − x P x ) 2

Abstract: In this study, we use nuclear magnetic resonance (NMR), high-resolution x-ray and neutron scattering to study structural and magnetic phase transitions in phosphorus-doped BaFe2(As1-xPx)2 Thus, previous transport, NMR, specific heat, and magnetic penetration depth measurements have provided compelling evidence for the presence of a quantum critical point (QCP) near optimal superconductivity at x = 03 However, we show that the tetragonal-to-orthorhombic structural (Ts) and paramagnetic to antiferromagnetic (AF, TN) transitions in BaFe2(As1-xPx)2 are always coupled and approach to TN ≈ Ts ≥ Tc (≈ 29 K) for x = 029 before vanishing abruptly for x ≥ 03 These results suggest that AF order in BaFe2(As1-xPx)2 disappears in a weakly first order fashion near optimal superconductivity, much like the electron-doped iron pnictides with an avoided QCP

Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells

Abstract: Diagnostic imaging delivering low doses of radiation often accompany human mesenchymal stem cells (MSCs)-based therapies. However, effects of low dose radiation on MSCs are poorly characterized. Here we examine patterns of phosphorylated histone H2AX (γH2AX) and phospho-S1981 ATM (pATM) foci formation in human gingiva-derived MSCs exposed to X-rays in time-course and dose-response experiments. Both γH2AX and pATM foci accumulated linearly with dose early after irradiation (5-60 min), with a maximum induction observed at 30-60 min (37 ± 3 and 32 ± 3 foci/cell/Gy for γH2AX and pATM, respectively). The number of γH2AX foci produced by intermediate doses (160 and 250 mGy) significantly decreased (40-60%) between 60 and 240 min post-irradiation, indicating rejoining of DNA double-strand breaks. In contrast, γH2AX foci produced by low doses (20-80 mGy) did not change after 60 min. The number of pATM foci between 60 and 240 min decreased down to control values in a dose-independent manner. Similar kinetics was observed for pATM foci co-localized with γH2AX foci. Collectively, our results suggest differential DNA double-strand break signaling and processing in response to low vs. intermediate doses of X-rays in human MSCs. Furthermore, mechanisms governing the prolonged persistence of γH2AX foci in these cells appear to be ATM-independent.

First-Order Melting of a Weak Spin-Orbit Mott Insulator into a Correlated Metal.

Abstract: The electronic phase diagram of the weak spin-orbit Mott insulator (${\mathrm{Sr}}_{1\ensuremath{-}x}{\mathrm{La}}_{x}{)}_{3}{\mathrm{Ir}}_{2}{\mathrm{O}}_{7}$ is determined via an exhaustive experimental study. Upon doping electrons via La substitution, an immediate collapse in resistivity occurs along with a narrow regime of nanoscale phase separation comprised of antiferromagnetic, insulating regions and paramagnetic, metallic puddles persisting until $x\ensuremath{\approx}0.04$. Continued electron doping results in an abrupt, first-order phase boundary where the N\'eel state is suppressed and a homogenous, correlated, metallic state appears with an enhanced spin susceptibility and local moments. As the metallic state is stabilized, a weak structural distortion develops and suggests a competing instability with the parent spin-orbit Mott state.

Fast neutron measurements using Cs 2 LiYCl 6 :Ce (CLYC) scintillator

Abstract: Samples of Cs2LiYCl6 :Ce (CLYC) scintillator have been characterized using monoenergetic neutron beams in the energy range 4.1–5.5 MeV. Four crystals with dimensions (thickness×diameter) of 1″×1″, 1″×2″, and 2″×2″ were evaluated, including one crystal with natural concentrations of Li isotopes and three that were enriched in 6 Li. The intrinsic efficiency of CLYC for fast-neutron detection has been determined for the natural-Li crystal. These measurements were translated into reaction cross-sections, and show good agreement with available cross-section data for neutron interactions with the 35Cl component of CLYC. Furthermore, it is shown that the charged-particle energy released in the fast-neutron reactions on 35 Cl varies linearly with the energy of the incoming neutron. These results verify the efficacy of CLYC for fast-neutron spectroscopy in a range of applications.

Low-dose irradiation affects expression of inflammatory markers in the heart of ApoE -/- mice.

Abstract: Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025–0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025–2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05–2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and intervention of radiation related, long-term side effects but also give important implications for low dose anti-inflammatory radiotherapy.

Limit on Tensor Currents from Li8 β Decay

Abstract: In the standard model, the weak interaction is formulated with a purely vector-axial-vector (V-A) structure. Without restriction on the chirality of the neutrino, the most general limits on tensor currents from nuclear β decay are dominated by a single measurement of the β-ν[over ¯] correlation in ^{6}He β decay dating back over a half century. In the present work, the β-ν[over ¯]-α correlation in the β decay of ^{8}Li and subsequent α-particle breakup of the ^{8}Be^{*} daughter was measured. The results are consistent with a purely V-A interaction and in the case of couplings to right-handed neutrinos (C_{T}=-C_{T}^{'}) limits the tensor fraction to |C_{T}/C_{A}|^{2}<0.011 (95.5% C.L.). The measurement confirms the ^{6}He result using a different nuclear system and employing modern ion-trapping techniques subject to different systematic uncertainties.

Evaluation of the annual Canadian biodosimetry network intercomparisons.

Abstract: Purpose: To evaluate the importance of annual intercomparisons for maintaining the capacity and capabilities of a well-established biodosimetry network in conjunction with assessing efficient and effective analysis methods for emergency response. Materials and methods: Annual intercomparisons were conducted between laboratories in the Canadian National Biological Dosimetry Response Plan. Intercomparisons were performed over a six-year period and comprised of the shipment of 10–12 irradiated, blinded blood samples for analysis by each of the participating laboratories. Dose estimates were determined by each laboratory using the dicentric chromosome assay (conventional and QuickScan scoring) and where possible the cytokinesis block micronucleus (CBMN) assay. Dose estimates were returned to the lead laboratory for evaluation and comparison. Results: Individual laboratories performed comparably from year to year with only slight fluctuations in performance. Dose estimates using the dicentric chromosome assay were accurate about 80% of the time and the QuickScan method for scoring the dicentric chromosome assay was proven to reduce the time of analysis without having a significant effect on the dose estimates. Although analysis with the CBMN assay was comparable to QuickScan scoring with respect to speed, the accuracy of the dose estimates was greatly reduced. Conclusions: Annual intercomparisons are necessary to maintain a network of laboratories for emergency response biodosimetry as they evoke confidence in their capabilities.

Interplay among solidification, microstructure, residual strain and hot tearing in B206 aluminum alloy

Abstract: Hot tearing is a complex phenomenon attributed to alloy solidification, microstructure and stress/strain development within a casting. In this research, the conditions associated with the formation of hot tears in B206 aluminum alloy were investigated. Neutron diffraction strain mapping was carried out on three B206 castings with varying levels of titanium (i.e. unrefined, 0.02 and 0.05 wt%). Titanium additions effectively reduced grain size and transformed grain morphology from coarse dendrites to fine globular grains. Further, thermal analysis suggested that grain refinement delayed the onset of dendrite coherency in B206 and therefore enhanced the duration of bulk liquid metal feeding for the refined casting conditions. As a result, the interactive effects of such factors resulted in a more uniform distribution of strain, and subsequent higher resistance to hot tearing for the grain refined castings.

A Jacobian-free Newton–Krylov method for thermalhydraulics simulations

Abstract: Summary The current paper is focused on investigating a Jacobian-free Newton–Krylov (JFNK) method to obtain a fully implicit solution for two-phase flows. In the JFNK formulation, the Jacobian matrix is not directly evaluated, potentially leading to major computational savings compared with a simple Newton's solver. The objectives of the present paper are as follows: (i) application of the JFNK method to two-fluid models; (ii) investigation of the advantages and disadvantages of the fully implicit JFNK method compared with commonly used explicit formulations and implicit Newton–Krylov calculations using the determination of the Jacobian matrix; and (iii) comparison of the numerical predictions with those obtained by the Canadian Algorithm for Thermaulhydraulics Network Analysis 4. Two well-known benchmarks are considered, the water faucet and the oscillating manometer. An isentropic two-fluid model is selected. Time discretization is performed using a backward Euler scheme. A Crank–Nicolson scheme is also implemented to check the effect of temporal discretization on the predictions. Advection Upstream Splitting Method+ is applied to the convective fluxes. The source terms are discretized using a central differencing scheme. One explicit and two implicit formulations, one with Newton's solver with the Jacobian matrix and one with JFNK, are implemented. A detailed grid and model parameter sensitivity analysis is performed. For both cases, the JFNK predictions are in good agreement with the analytical solutions and explicit profiles. Further, stable results can be achieved using high CFL numbers up to 200 with a suitable choice of JFNK parameters. The computational time is significantly reduced by JFNK compared with the calculations requiring the determination of the Jacobian matrix. Copyright © 2015 John Wiley & Sons, Ltd.

Pulsed Eddy Current Inspection of Support Structures in Steam Generators

Abstract: Degradation and fouling of support structures in nuclear steam generators (SGs) can lead to SG tube damage and loss of SG efficiency. Inspection and monitoring of support structures combined with preventative maintenance programs can alleviate these effects and extend SG life. Conventional eddy current inspection technologies are extensively used for detecting and sizing indications from wall loss, frets at supports, cracks and other degradation modes in the tubes, as well as assessing the condition of support structures. However, these methods have limited capabilities when more than one degradation mode is present simultaneously, or when combined with fouling. Pulsed eddy current combined with principal components analysis (PCA) was examined for inspection of 15.9 mm (5/ $8^{{\prime }{\prime }}$ ) Alloy-800 tubes and surrounding stainless steel (SS410) support structures. Clear separation of PCA scores associated with tubes from those associated with ferromagnetic SS410 supports permitted measurement of tube-to-support gaps, in either the presence of tube fretting or variation of relative position of the tube within SS410 supports. For concentric tubes, frets could be sized independently of SS410 hole diameter variations, which in other materials could represent support corrosion. Capability to clearly separate scores was attributed to large differences in relaxation times for diffusion of transient fields through the tube compared with diffusion into the ferromagnetic support structure.

Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to X-ray radiation

Abstract: // Andreyan N. Osipov 1, 2, 3, 4 , Anna Grekhova 1, 5 , Margarita Pustovalova 1, 2 , Ivan V. Ozerov 1 , Petr Eremin 1 , Natalia Vorobyeva 1, 3 , Natalia Lazareva 1 , Andrey Pulin 1 , Alex Zhavoronkov 4, 6, 7 , Sergey Roumiantsev 3, 4, 8 , Dmitry Klokov 9 , Ilya Eremin 1 1 State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia 2 Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow 119991, Russia 3 Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow 117997, Russia 4 Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region 141700, Russia 5 Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Moscow 119991, Russia 6 Insilico Medicine, Inc, ETC, Johns Hopkins University, Baltimore, MD 21218, USA 7 The Biogerontology Research Foundation, BGRF, London W1J 5NE, UK 8 N.I. Pirogov Russian National Research Medical University, Moscow 117997, Russia 9 Canadian Nuclear Laboratories, Chalk River, ON K0J1P0, Canada Correspondence to: Andreyan N. Osipov, e-mail: andreyan.osipov@gmail.com Keywords: DNA DSB repair, homologous recombination, human fibroblasts, X-rays, continuous irradiation Received: April 08, 2015 Accepted: July 31, 2015 Published: August 13, 2015 ABSTRACT Molecular and cellular responses to protracted ionizing radiation exposures are poorly understood. Using immunofluorescence microscopy, we studied the kinetics of DNA repair foci formation in normal human fibroblasts exposed to X-rays at a dose rate of 4.5 mGy/min for up to 6 h. We showed that both the number of γH2AX foci and their integral fluorescence intensity grew linearly with time of irradiation up to 2 h. A plateau was observed between 2 and 6 h of exposure, indicating a state of balance between formation and repair of DNA double-strand breaks. In contrast, the number and intensity of foci formed by homologous recombination protein RAD51 demonstrated a continuous increase during 6 h of irradiation. We further showed that the enhancement of the homologous recombination repair was not due to redistribution of cell cycle phases. Our results indicate that continuous irradiation of normal human cells triggers DNA repair responses that are different from those elicited after acute irradiation. The observed activation of the error-free homologous recombination DNA double-strand break repair pathway suggests compensatory adaptive mechanisms that may help alleviate long-term biological consequences and could potentially be utilized both in radiation protection and medical practices.

Water Uptake and Swelling Hysteresis in a Nafion Thin Film Measured with Neutron Reflectometry

Abstract: Water uptake and swelling in a thin (∼15 nm) Nafion film on SiO2 native oxide on a Si wafer is studied as a function of relative humidity (8–97%) at room temperature and as a function of temperature (25–60 °C) at 97% relative humidity by neutron reflectometry. This is the first report on the behavior of thin Nafion films at elevated temperatures and high humidity. Large hysteresis is observed during the temperature cycle. The observed swelling strain in the film at 60 °C is 48% as compared to the as-deposited state, which is far above any previously observed trend at room temperature. A small decrease in the average SLD suggests that part of the additional swelling is due to thermal expansion, but the estimated D2O/SO3 ratio also increases by 70%. Half of the “excess” absorption and 73% of the additional swelling are retained during cooling back to room temperature. The results provide new insights into the dynamics of Nafion on nanometer scales under fuel cell operating conditions.

A Cs 2 LiYCl 6 :Ce-based advanced radiation monitoring device

Abstract: Cs 2 LiYCl 6 :Ce 3+ (CLYC) scintillator has gained recent interest because of its ability to perform simultaneous gamma spectroscopy and thermal neutron detection. Discrimination between the two incident particle types owes to the fundamentally unique emission waveforms, a consequence of the interaction and subsequent scintillation mechanisms within the crystal. Due to this dual-mode detector capability, CLYC was selected for the development of an Advanced Radiation Monitoring Device (ARMD), a compact handheld instrument for radioisotope identification and localization. ARMD consists of four 1 in.-right cylindrical CLYC crystals, custom readout electronics including a suitable multi-window application specific integrated circuit (ASIC), battery pack, proprietary software, and Android-based tablet for high-level analysis and display. We herein describe the motivation of the work and engineering design of the unit, and we explain the software embedded in the core module and for radioisotope analysis. We report an operational range of tens of keV to 8.5 MeV with approximately 5.3% gamma energy resolution at 662 keV, thermal neutron detection efficiency of 10%, battery lifetime of up to 10 h, manageable rates of 20 kHz; further, we describe in greater detail time to identify specific gamma source setups.

Mott-Kondo insulator behavior in the iron oxychalcogenides

Abstract: We perform a combined experimental-theoretical study of the Fe-oxychalcogenides (FeOCh) series La2O2Fe2OM2 (M=S, Se), which are among the latest Fe-based materials with the potential to show unconventional high-Tc superconductivity (HTSC). A combination of incoherent Hubbard features in x-ray absorption and resonant inelastic x-ray scattering spectra, as well as resistivity data, reveal that the parent FeOCh are correlation-driven insulators. To uncover microscopics underlying these findings, we perform local density approximation-plus-dynamical mean field theory (LDA+DMFT) calculations that reveal a novel Mott-Kondo insulating state. Based upon good agreement between theory and a range of data, we propose that FeOCh may constitute an ideal testing ground to explore HTSC arising from a strange metal proximate to a novel selective-Mott quantum criticality.

Differential Molecular Stress Responses to Low Compared to High Doses of Ionizing Radiation in Normal Human Fibroblasts.

Abstract: Understanding the mechanisms producing low dose ionizing radiation specific biological effects represents one of the major challenges of radiation biology. Although experimental evidence does suggest that various molecular stress response pathways may be involved in the production of low dose effects, much of the detail of those mechanisms remains elusive. We hypothesized that the regulation of various stress response pathways upon irradiation may differ from one another in complex dose-response manners, causing the specific and subtle low dose radiation effects. In the present study, the transcription level of 22 genes involved in stress responses were analyzed using RT-qPCR in normal human fibroblasts exposed to a range of gamma-doses from 1 to 200 cGy. Using the alkali comet assay, we also measured the level of DNA damages in dose-response and time-course experiments. We found non-linear dose responses for the repair of DNA damage after exposure to gamma-radiation. Alterations in gene expression were also not linear with dose for several of the genes examined and did not follow a single pattern. Rather, several patterns could be seen. Our results suggest a complex interplay of various stress response pathways triggered by low radiation doses, with various low dose thresholds for different genes.