WorldWideScience

Sample records for low-dose sarin exposure

  1. The effects of repeated low-dose sarin exposure

    International Nuclear Information System (INIS)

    Shih, T.-M.; Hulet, S.W.; McDonough, J.H.

    2006-01-01

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD 5 dose of sarin (42 μg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD 5 of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD 5 of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD 5 sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD 5 sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD 5 sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD 5 sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD 5 doses of sarin failed to

  2. The Potential Neurotoxic Effects of Low-Dose Sarin Exposure in a Guinea Pig Model

    Science.gov (United States)

    2002-01-01

    1 THE POTENTIAL NEUROTOXIC EFFECTS OF LOW-DOSE SARIN EXPOSURE IN A GUINEA PIG MODEL Melinda R. Roberson, PhD, Michelle B. Schmidt...Proving Ground, MD 21010 USA ABSTRACT This study is assessing the effects in guinea pigs of repeated low-dose exposure to the nerve...COVERED - 4. TITLE AND SUBTITLE The Potential Neurotoxic Effects Of Low-Dose Sarin Exposure In A Guinea Pig Model 5a. CONTRACT NUMBER 5b

  3. The Effects of Repeated Low-Dose Sarin Exposure

    Science.gov (United States)

    2005-08-01

    support the idea that there is a triphasic NT model for onset and progression of seizures and subsequent brain damage upon acute exposure to OP ChE...An ACh microbore column (1x530 mm ID, 10 µm UniJet, BAS #MF-8904) coupled with AChE/choline oxidase immobilized enzyme reactor (BAS # MF-8903) was...peroxidase to the electrode for the reduction of hydrogen peroxide that was generated from the immobilized enzyme reactor . The detector was set at (-)1.0

  4. Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs.

    Science.gov (United States)

    Smith, C D; Lee, R B; Moran, A V; Sipos, M L

    2016-01-01

    Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period. Published by Elsevier Inc.

  5. Low Dose Sarin Leads To Murine Cardiac Dysfunction

    Science.gov (United States)

    2010-03-01

    hypoxia resulting from bronco -constriction also affects the cardiovascular system by reinforcing sympathetic tone, while ACh induced epinephrine...3000 4000 5000 6000 7000 8000 Septum LV Wall Total LV Ca rd io m yo cy te Si ze (P ix el s/ nu cl ei ) Control 0.4 LD50 0.5 LD50 * pɘ.05 vs... el s/ nu cl ei ) Control Sarin (Combined Groups) * pɘ.05 vs. control ** pɘ.01 vs. control † pɘ.001 vs. control 59 Results of Collagen

  6. Sarin

    Science.gov (United States)

    ... killers) called organophosphates in terms of how they work and what kind of harmful effects they cause. However, nerve agents are much more ... 106(1): 55-62, 2013. Sarin Causes Autonomic Imbalance and Cardiomyopathy: An ... Technol. Biomed. Life Sci., 2010, 878, 1207–1215. Smart JK. History ...

  7. Biological Effects of Low-Dose Exposure

    CERN Document Server

    Komochkov, M M

    2000-01-01

    On the basis of the two-protection reaction model an analysis of stochastic radiobiological effects of low-dose exposure of different biological objects has been carried out. The stochastic effects are the results published in the last decade: epidemiological studies of human cancer mortality, the yield of thymocyte apoptosis of mice and different types of chromosomal aberrations. The results of the analysis show that as dependent upon the nature of biological object, spontanous effect, exposure conditions and radiation type one or another form dose - effect relationship is realized: downwards concave, near to linear and upwards concave with the effect of hormesis included. This result testifies to the incomplete conformity of studied effects of 1990 ICRP recomendations based on the linear no-threshold hypothesis about dose - effect relationship. Because of this the methodology of radiation risk estimation recomended by ICRP needs more precisian and such quantity as collective dose ought to be classified into...

  8. Exposure to low doses of ionizing radiations

    International Nuclear Information System (INIS)

    Le Guen, B.

    2008-01-01

    The author discusses the knowledge about the effects of ionizing radiations on mankind. Some of them have been well documented (skin cancer and leukaemia for the pioneer scientists who worked on radiations, some other types of cancer for workers who handled luminescent paints, rock miners, nuclear explosion survivors, patients submitted to radiological treatments). He also evokes the issue of hereditary cancers, and discusses the issue of low dose irradiation where some surveys can now be performed on workers. He discusses the biological effects of these low doses. He outlines that many questions remain about these effects, notably the influence of dose level and of dose rate level on the biological reaction

  9. Radiation effects after low dose chronic long-term exposure

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Friesecke, I.

    1997-01-01

    This document approaches the radiation effects after low dose chronic long-term exposure, presenting examples occurred, the pathophysiologic mechanisms for cell system tolerance in elevated radiation fields, and the diagnostic and therapeutic possibilities

  10. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

  11. Lymphocytic subsets and low-dose exposure

    International Nuclear Information System (INIS)

    Tuschl, H.; Kovac, R.; Eybl, E.

    1993-03-01

    The present investigations proved the differential radiosensitivity of lymphocytic subpopulations: From in vivo and in vitro irradiations it may be followed that the most sensitive subset are CD8 positive suppressor T cells. CD4/CD8 ratios are increased both in peripheral blood and after mitogen stimulation of lymphocytes of exposed persons. The decrease in B cells is pronounced only at higher radiation doses. Though the rate of DNA synthesis after mitogen stimulation was reduced in some exposed persons, that was no general phenomenon. Especially after tritium exposure, the observed lymphopenia correlated with an increased stimulation by PHA and an increased rate of DNA synthesis in some probands. Thus the present investigations indicate that - despite an inhibition of some immune parameters by radioexposure - the body is able to maintain its immunological homoeostasis. (authors)

  12. Biological effects of low-dose ionizing radiation exposure

    International Nuclear Information System (INIS)

    Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst

    2009-01-01

    The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

  13. Fruit-flies in low-dose exposure experiments

    International Nuclear Information System (INIS)

    Zajnullin, V.G.; Moskalev, A.A.; Shaposhnikov, M.V.; Sheptyakova, A.I.

    2002-01-01

    In vivo exposure of fruit-flies of Drosophila melanogaster line to low doses provided new data indicating that mechanisms of induced genetic instability are involved in radiation-induced alteration of genotype. It is true for increase of genetic variance due to change in transposition number, for change in adaptation capabilities due to modification of gene expression, and for mutability-associated reparation and apoptosis. (author)

  14. Plants as warning signal for exposure to low dose radiation

    International Nuclear Information System (INIS)

    Rusli Ibrahim; Norhafiz Talib

    2012-01-01

    The stamen-hair system of Tradescantia for flower colour has proven to be one of the most suitable materials to study the frequency of mutations induced by low doses of various ionizing radiations and chemical mutagens. The system has also been used successfully for detecting mutagenic synergisms among chemical mutagens and ionizing radiations as well as for studying the variations of spontaneous mutation frequency. In this study of radiobiology, the main objective is to observe somatic mutation (occurrence of pink cells from blue cells) induced on stamen hairs of five Tradescantia sp. available in Malaysia after exposure to low doses of chronic gamma irradiation using Gamma Green House. Pink cells appeared only on Tradescantia Pallida Purpurea stamen hairs after 13 days of exposure to irradiation with different doses of gamma rays. The highest number of stamens with pink cells was recorded from flowers irradiated with the highest dose of 6.37 Gy with 0.07 Gy/ h of dose rate. The lowest number of stamens with pink cells was recorded with an average of 0.57, irradiated with the lowest dose of 0.91 Gy with 0.01 Gy/ h of dose rate. There were no pink cells observed on Tradescantia Spathaceae Discolor after exposure to different doses of gamma rays. Similar negative results were observed for the control experiments. The principal cells in this assay are the mitotic stamen hair cells developing in the young flower buds. After exposure to radiation, the heterozygous dominant blue character of the stamen hair cell is prevented, resulting in the appearance of the recessive pink color. Furthermore, no pink cell appears on all species of Tradescantia spathaceae after irradiated with different doses of gamma rays. The sensitivity of the Tradescantia has been used widely and has demonstrated the relation between radiation dose and frequency of mutation observed at low doses which can contribute to the effects of low doses and their consequences for human health. This system

  15. Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs

    International Nuclear Information System (INIS)

    Che, Magnus M.; Conti, Michele; Chanda, Soma; Boylan, Megan; Sabnekar, Praveena; Rezk, Peter; Amari, Ethery; Sciuto, Alfred M.; Gordon, Richard K.; Doctor, Bhupendra P.; Nambiar, Madhusoodana P.

    2009-01-01

    We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m 3 sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.

  16. Global DNA methylation responses to low dose radiation exposure

    International Nuclear Information System (INIS)

    Newman, M.R.; Ormsby, R.J.; Blyth, B.J.; Sykes, P.J.; Bezak, E.

    2011-01-01

    Full text: High radiation doses cause breaks in the DNA which are considered the critical lesions in initiation of radiation-induced cancer. However, at very low radiation doses relevant for the general public, the induction of such breaks will be rare, and other changes to the DNA such as DNA methylation which affects gene expression may playa role in radiation responses. We are studying global DNA methylation after low dose radiation exposure to determine if low dose radiation has short- and/or long-term effects on chromatin structure. We developed a sensitive high resolution melt assay to measure the levels of DNA methylation across the mouse genome by analysing a stretch of DNA sequence within Long Interspersed Nuclear Elements-I (LINE I) that comprise a very large proportion of the mouse and human genomes. Our initial results suggest no significant short-term or longterm) changes in global NA methylation after low dose whole-body X-radiation of 10 J1Gyor 10 mGy, with a significant transient increase in NA methylation observed I day after a high dose of I Gy. If the low radiation doses tested are inducing changes in bal DNA methylation, these would appear to be smaller than the variation observed between the sexes and following the general stress of the sham-irradiation procedure itself. This research was funded by the Low Dose Radiation Research Program, Biological and Environmental Research, US DOE, Grant DE-FG02-05ER64104 and MN is the recipient of the FMCF/BHP Dose Radiation Research Scholarship.

  17. Exposures at low doses and biological effects of ionizing radiations

    International Nuclear Information System (INIS)

    Masse, R.

    2000-01-01

    Everyone is exposed to radiation from natural, man-made and medical sources, and world-wide average annual exposure can be set at about 3.5 mSv. Exposure to natural sources is characterised by very large fluctuations, not excluding a range covering two orders of magnitude. Millions of inhabitants are continuously exposed to external doses as high as 10 mSv per year, delivered at low dose rates, very few workers are exposed above the legal limit of 50 mSv/year, and referring to accidental exposures, only 5% of the 116 000 people evacuated following the Chernobyl disaster encountered doses above 100 mSv. Epidemiological survey of accidentally, occupationally or medically exposed groups have revealed radio-induced cancers, mostly following high dose-rate exposure levels, only above 100 mSv. Risk coefficients were derived from these studies and projected into linear models of risk (linear non-threshold hypothesis: LNT), for the purpose of risk management following exposures at low doses and low dose-rates. The legitimacy of this approach has been questioned, by the Academy of sciences and the Academy of medicine in France, arguing: that LNT was not supported by Hiroshima and Nagasaki studies when neutron dose was revisited; that linear modelling failed to explain why so many site-related cancers were obviously nonlinearly related to the dose, and especially when theory predicted they ought to be; that no evidence could be found of radio-induced cancers related to natural exposures or to low exposures at the work place; and that no evidence of genetic disease could be shown from any of the exposed groups. Arguments were provided from cellular and molecular biology helping to solve this issue, all resulting in dismissing the LNT hypothesis. These arguments included: different mechanisms of DNA repair at high and low dose rate; influence of inducible stress responses modifying mutagenesis and lethality; bystander effects allowing it to be considered that individual

  18. Low dose TBT exposure decreases amphipod immunocompetence and reproductive fitness.

    Science.gov (United States)

    Jacobson, Therese; Sundelin, Brita; Yang, Gongda; Ford, Alex T

    2011-01-17

    The antifouling agent tributyltin (TBT) is a highly toxic pollutant present in many aquatic ecosystems. Despite of regulations on the usage of TBT, it remains in high concentrations in sediments both in harbors and in off-shore sites. The toxicity of TBT in mollusks is well documented. However, adverse effects in other aquatic organisms, such as crustaceans, are less well known. This study is an effort to assess the effects of environmentally realistic concentrations of TBT on an ecologically important species in Swedish fresh and brackish water ecosystems, the benthic amphipod Monoporeia affinis. Field collected animals were exposed during gonad maturation to TBT (70 and 170 ng/g sediment d wt) for five weeks in static microcosms with natural sediment. Exposure concentrations were chosen to reflect effects at concentrations found in Swedish coastal sediment, but below expected effects on survival. TBT exposure resulted in a statistically significant adverse effect on oocyte viability and a doubling of the prevalence of microsporidian parasites in females, from 17% in the control to 34% in the 170 ng TBT/g sediment d wt exposure. No effects on survival were observed. Borderline significant effects were observed on male sexual maturation in the 70 ng TBT/g d wt exposure and on ecdysteroid levels in the 170 ng/g sediment d wt exposure. Both reproduction and parasite infection effects are of ecological importance since they have the potential to affect population viability in the field. This study gives further evidence to the connection between low dose contaminant exposure and increases in microsporidian parasite infection. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Health Effects of Exposure to Low Dose of Radiation

    International Nuclear Information System (INIS)

    Alatas, Zubaidah

    2003-01-01

    Human beings are exposed to natural radiation from external sources include radionuclides in the earth and cosmic radiation, and by internal radiation from radionuclides, mainly uranium and thorium series, incorporated into the body. Living systems have adapted to the natural levels of radiation and radioactivity. But some industrial practices involving natural resources enhance these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Biological effects of ionizing radiation are the outcomes of physical and chemical processes that occur immediately after the exposure, then followed by biological process in the body. These processes will involve successive changes in the molecular, cellular, tissue and whole organism levels. Any dose of radiation, no matter how small, may produce health effects since even a single ionizing event can result in DNA damage. The damage to DNA in the nucleus is considered to be the main initiating event by which radiation causes damage to cells that results in the development of cancer and hereditary disease. It has also been indicated that cytogenetic damage can occur in cells that receive no direct radiation exposure, known as bystander effects. This paper reviews health risks of low dose radiation exposure to human body causing stochastic effects, i.e. cancer induction in somatic cells and hereditary disease in genetic cells. (author)

  20. Lyssavirus infection: 'low dose, multiple exposure' in the mouse model.

    Science.gov (United States)

    Banyard, Ashley C; Healy, Derek M; Brookes, Sharon M; Voller, Katja; Hicks, Daniel J; Núñez, Alejandro; Fooks, Anthony R

    2014-03-06

    The European bat lyssaviruses (EBLV-1 and EBLV-2) are zoonotic pathogens present within bat populations across Europe. The maintenance and transmission of lyssaviruses within bat colonies is poorly understood. Cases of repeated isolation of lyssaviruses from bat roosts have raised questions regarding the maintenance and intraspecies transmissibility of these viruses within colonies. Furthermore, the significance of seropositive bats in colonies remains unclear. Due to the protected nature of European bat species, and hence restrictions to working with the natural host for lyssaviruses, this study analysed the outcome following repeat inoculation of low doses of lyssaviruses in a murine model. A standardized dose of virus, EBLV-1, EBLV-2 or a 'street strain' of rabies (RABV), was administered via a peripheral route to attempt to mimic what is hypothesized as natural infection. Each mouse (n=10/virus/group/dilution) received four inoculations, two doses in each footpad over a period of four months, alternating footpad with each inoculation. Mice were tail bled between inoculations to evaluate antibody responses to infection. Mice succumbed to infection after each inoculation with 26.6% of mice developing clinical disease following the initial exposure across all dilutions (RABV, 32.5% (n=13/40); EBLV-1, 35% (n=13/40); EBLV-2, 12.5% (n=5/40)). Interestingly, the lowest dose caused clinical disease in some mice upon first exposure ((RABV, 20% (n=2/10) after first inoculation; RABV, 12.5% (n=1/8) after second inoculation; EBLV-2, 10% (n=1/10) after primary inoculation). Furthermore, five mice developed clinical disease following the second exposure to live virus (RABV, n=1; EBLV-1, n=1; EBLV-2, n=3) although histopathological examination indicated that the primary inoculation was the most probably cause of death due to levels of inflammation and virus antigen distribution observed. All the remaining mice (RABV, n=26; EBLV-1, n=26; EBLV-2, n=29) survived the tertiary and

  1. Long-Term Effects of Subchronic Exposure to Sarin, Alone and With Stress or Other Chemicals

    National Research Council Canada - National Science Library

    Abou-Donia, Mohamed

    2002-01-01

    ...) and stress on the development of chronic and neurologic deficits. An important finding from our studies is that brain AChE and plasma BChE inhibition might be used as a biomarker for exposure, not for sarin-induced neurologic deficits...

  2. Relationship to carcinogenesis of repetitive low-dose radiation exposure

    International Nuclear Information System (INIS)

    Ootsuyama, Akira

    2016-01-01

    We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose. (author)

  3. Global Gene Expression Profiling of Human Genome Following Exposure to Sarin and Soman

    International Nuclear Information System (INIS)

    Gopalakrishnakone, P.; Pachiappan, A.; Srinivasan, K. N.; Loke, W. K.; Lee, F. K.

    2007-01-01

    Toxicogenomics merges genomics with toxicology is a rapidly expanding field on the assumption that the transcriptional responses of cells to different toxic exposure are sufficiently distinct robust and reproducible to discriminate toxin from different families/classes which can be called as 'fingerprints' or 'Atlases'. In this study chemical weapons sarin was studied in a time and dose dependent manner after exposure to human neuroblastoma cell line. (Sarin or GB) exerts its effect through inhibition of acetylcholinesterase activity and induction of delayed neurotoxicity in a dose [EC 50 50 ppm, (around 372.4 μM)] and time-dependent manner. The effect and/or the mechanism of single or repeated exposures to GB, however, are less clear and yet to be explored at cellular level. The present study aims to scrutinize, the global gene expression profile following sarin toxicity in neuronal cells using Affymetrix-GeneChips. A tim-course study on the effect of a single (3 or 24h) or repeated (24 or 48h) doses of sarin (5ppm) on SHSY5Y cells was carried out. Using GeneSpring (PCA) analysis, 550 genes whose expression was significantly (p less than 0.01) altered by at least 2.5-fold, were selected. The results indicate that the low-level single dose exposure do not always parallel acute toxicity, but can cause a reversible down-regulation of genes and a range of anti-cholinesterase effects. In contrast, repeated doses produced persistent irreversible down-regulation of genes related to neurodegenerative mechanism at 48h. Real-time PCR and western blot analysis confirmed the reduced expression of presenilin 1 (TMP21), 2 and dopa.decarboxylase (DDC) mRNA and proteins. Besides providing an in vitro experimental model for studies on the neuropathophysiology and brain cells this investigation indicate possible mechanisms by which sarin could mediate neuro-degeneration. A comparison will be made with similar study with soman. (author)

  4. Total Risk Management for Low Dose Radiation Exposures

    International Nuclear Information System (INIS)

    Simic, Z.; Mikulicic, V.; Sterc, D.

    2012-01-01

    Our civilization is witnessing about century of nuclear age mixed with enormous promises and cataclysmic threats. Nuclear energy seems to encapsulate both potential for pure good and evil or at least we humans are able to perceive that. These images are continuously with us and they are both helping and distracting from making best of nuclear potentials for civilization. Today with nuclear use significantly present and with huge potential to further improve our life with energy and medical use it is of enormous importance to try to have calmed, rational, and objective view on potential risks and certain benefits. Because all use of nuclear energy proved that their immediate risks are negligible (i.e., Three Mile Island and Fukushima) or much smaller than from the other alternatives (i.e., Chernobyl) it seems that the most important issue is the amount of risk from the long term effects to people from exposure to small doses of radiation. A similar issue is present in the increased use of modern computational tomography and other radiation sources use in medicine for examination and therapy. Finally, extreme natural exposures are third such potential risk sources. Definition of low doses varies depending on the way of delivery (i.e., single, multiple or continuous exposures), and for this paper usual dose of 100 mSv is selected as yearly upper amount. There are three very different scientifically supported views on the potential risks from the low doses exposure. The most conservative theory is that all radiation is harmful, and even small increments from background levels (i.e., 2-3 mSv) present additional risk. This view is called linear no threshold theory (LNT) and it is accepted as a regulatory conservative simple approach which guarantees safety. Risk is derived from the extrapolation of the measured effects of high levels of radiation. Opposite theory to LNT is hormesis which assumes that in fact small doses of radiation are helpful and they are improving our

  5. Neurophysiologic and Neuropathologic Effects in Monkeys of Low Level Exposures to Sarin, Pyridostigmine, Pesticides and Botulinum Toxoid

    National Research Council Canada - National Science Library

    Olson, Carl

    1998-01-01

    .... Pilot studies are being performed to select doses of pyridostigmine bromide (PB), chlorpyrifos (CPF), and sarin (GE) to be used in two-week exposures with a 9-month post-dosing evaluation period...

  6. Assay techniques for detection of exposure to sulfur mustard, cholinesterase inhibitors, sarin, soman, GF, and cyanide. Technical bulletin

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-05-01

    This technical bulletin provides analytical techniques to identify toxic chemical agents in urine or blood samples. It is intended to provide the clinician with laboratory tests to detect exposure to sulfur mustard, cholinesterase inhibitors, sarin, soman, GF, and cyanide.

  7. Exposure to low dose ionising radiation: Molecular and clinical consequences.

    LENUS (Irish Health Repository)

    Martin, Lynn M

    2014-07-10

    This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HRS and the impact of HRS on the cellular response to radiation in mammalian cells. Particular attention is paid to the balance of evidence suggesting a role for DNA repair processes in the response, evidence suggesting a role for the cell cycle checkpoint processes, and evidence investigating the clinical implications\\/relevance of the effect.

  8. Injury of the blood-testies barrier after low-dose-rate chronic radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Young Hoon; Bae Min Ji; Lee, Chang Geun; Yang, Kwang Mo; Jur, Kyu; Kim, Jong Sun [Dongnam Institute of Radiological and Medical Science, Busan (Korea, Republic of)

    2014-04-15

    The systemic effect of radiation increases in proportionally with the dose and dose rate. Little is known concerning the relationships between harmful effects and accumulated dose, which is derived from continuous low-dose rate radiation exposure. Recent our studies show that low-dose-rate chronic radiation exposure (3.49 mGy/h) causes adverse effects in the testis at a dose of 2 Gy (6 mGy/h). However, the mechanism of the low-dose-rate 2 Gy irradiation induced testicular injury remains unclear. The present results indicate that low-dose rate chronic radiation might affect the BTB permeability, possibly by decreasing levels of ZO-1, Occludin-1, and NPC-2. Furthermore, our results suggest that there is a risk of male infertility through BTB impairment even with low-dose-rate radiation if exposure is continuous.

  9. Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

    International Nuclear Information System (INIS)

    Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel; Chapman, Shira; Bloch-Shilderman, Eugenia; Grauer, Ettie

    2016-01-01

    Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. In all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.

  10. Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

    Energy Technology Data Exchange (ETDEWEB)

    Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel; Chapman, Shira; Bloch-Shilderman, Eugenia; Grauer, Ettie, E-mail: ettieg@iibr.gov.il

    2016-11-01

    Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. In all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.

  11. Low dose radiation exposure and atherosclerosis in ApoE{sup -/-} mice

    Energy Technology Data Exchange (ETDEWEB)

    Mitchel, R.E.J. [Atomic Energy of Canada Limited, Chalk River, ON (Canada); Hasu, M. [Univ. of Ottawa, Department of Pathology and Lab. Medicine, and Cellular and Molecular Medicine, Ottawa, ON (Canada); Univ. of Ottawa Heart Inst., Vascular Biology Group, Ottawa, ON (Canada); Bugden, M.; Wyatt, H. [Atomic Energy of Canada Limited, Chalk River, ON (Canada); Little, M. [Imperial Coll., Faculty of Medicine, St. Marys Campus, London (United Kingdom); Hildebrandt, G. [Univ. Hospital, Dept. of Radiotherapy, Rostock (Germany); Priest, N.D. [Atomic Energy of Canada Limited, Chalk River, ON (Canada); Whitman, S.C. [Univ. of Ottawa, Department of Pathology and Lab. Medicine, and Cellular and Molecular Medicine, Ottawa, ON (Canada); Univ. of Ottawa Heart Inst., Vascular Biology Group, Ottawa, ON (Canada)

    2010-07-01

    The hypothesis that single low dose exposures (0.025-0.5 Gy) to low LET radiation, given at either high (240 mGy/min) or low (1 mGy/min) dose rate, would promote aortic atherosclerosis was tested in female C57BI/6 mice genetically predisposed to this disease (ApoE-/-). Mice were exposed either at early stage disease (2 months of age) and examined 3 or 6 months later, or at late stage disease (8 months of age) and examined 2 or 4 months later. Compared to unexposed controls, all doses given at low or high dose rate at early stage disease had significant inhibitory effects on lesion growth and, at 25 or 50 mGy, on lesion frequency. No dose given at low dose rate had any effect on total serum cholesterol, but this was elevated by every dose given at high dose rate. Exposures at low dose rate had no effect on the percentage of lesion lipids contained within macrophages, and, at either high or low dose rate, had no significant effect on lesion severity. Exposure at late stage disease, to any dose at high dose rate, had no significant effect on lesion frequency, but at low dose rate some doses produced a small transient increase in this frequency. Exposure to low doses at low, but not high dose rate, significantly, but transiently reduced average lesion size, and at either dose rate transiently reduced lesion severity. Exposure to any dose at low dose rate (but not high dose rate) resulted in large and persistent decreases in serum cholesterol. These data indicate that a single low dose exposure, depending on dose and dose rate, generally protects against various measures of atherosclerosis in genetically susceptible mice. This result contrasts with the known, generally detrimental effects of high doses on this disease in the same mice, suggesting that a linear extrapolation of risk from high doses is not appropriate. (author)

  12. Low dose radiation exposure and atherosclerosis in ApoE-/- mice

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Hasu, M.; Bugden, M.; Wyatt, H.; Little, M.; Hildebrandt, G.; Priest, N.D.; Whitman, S.C.

    2010-01-01

    The hypothesis that single low dose exposures (0.025-0.5 Gy) to low LET radiation, given at either high (240 mGy/min) or low (1 mGy/min) dose rate, would promote aortic atherosclerosis was tested in female C57BI/6 mice genetically predisposed to this disease (ApoE-/-). Mice were exposed either at early stage disease (2 months of age) and examined 3 or 6 months later, or at late stage disease (8 months of age) and examined 2 or 4 months later. Compared to unexposed controls, all doses given at low or high dose rate at early stage disease had significant inhibitory effects on lesion growth and, at 25 or 50 mGy, on lesion frequency. No dose given at low dose rate had any effect on total serum cholesterol, but this was elevated by every dose given at high dose rate. Exposures at low dose rate had no effect on the percentage of lesion lipids contained within macrophages, and, at either high or low dose rate, had no significant effect on lesion severity. Exposure at late stage disease, to any dose at high dose rate, had no significant effect on lesion frequency, but at low dose rate some doses produced a small transient increase in this frequency. Exposure to low doses at low, but not high dose rate, significantly, but transiently reduced average lesion size, and at either dose rate transiently reduced lesion severity. Exposure to any dose at low dose rate (but not high dose rate) resulted in large and persistent decreases in serum cholesterol. These data indicate that a single low dose exposure, depending on dose and dose rate, generally protects against various measures of atherosclerosis in genetically susceptible mice. This result contrasts with the known, generally detrimental effects of high doses on this disease in the same mice, suggesting that a linear extrapolation of risk from high doses is not appropriate. (author)

  13. Low-level exposure of guinea pigs and marmosets to sarin vapour in air: Lowest-observable-adverse-effect level (LOAEL) for miosis

    NARCIS (Netherlands)

    Helden, H.P.M. van; Trap, H.C.; Kuijpers, W.C.; Oostdijk, J.P.; Benschop, H.P.; Langenberg, J.P.

    2004-01-01

    The purpose of this pilot study was to indicate, for low-level exposure of conscious guinea pigs and marmoset monkeys to sarin vapour in air, the lowest-observable-adverse-effect level (LOAEL) of sarin for miosis. This is the concentration × time (C·t) value (t = 5 h) of exposure at which miosis

  14. Protection against soman and sarin exposure by transdermal physostigmine and scopolamine

    Energy Technology Data Exchange (ETDEWEB)

    Meshulam, Y.; Davidovici, R.; Levy, A.

    1993-05-13

    The purpose of this study was to evaluate the prophylactic efficacy of physostigmine (physo), administered via sustained release (SR) methods, with and without scopolamine, against soman and sarin exposure in guinea-pigs. Transdermal physo pad (3 sq cm/kg; 60-80 ug/sq cm), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 hours before exposure to the cholinesterase (ChE) inhibitors. At the time of exposure, physo concentrations in brain and plasma were 3.6 ng/g and 4.1 ng/ml respectively. Brain and whole blood ChE activity were inhibited to 70% and 57% of their original activity. Transdermal physo by itself protected up to 70% of the animals exposed to 1.5 LD(50) of soman or sarin (100% mortality was recorded in the control group). Combining transdermal physo with Scopoderm (by Ciba Geigy Inc.) provided full protection against 1.5 LD(50).

  15. A systematic review of Bisphenol A "low dose" studies in the context of human exposure: a case for establishing standards for reporting "low-dose" effects of chemicals.

    Science.gov (United States)

    Teeguarden, Justin G; Hanson-Drury, Sesha

    2013-12-01

    Human exposure to the chemical Bisphenol A is almost ubiquitous in surveyed industrialized societies. Structural features similar to estrogen confer the ability of Bisphenol A (BPA) to bind estrogen receptors, giving BPA membership in the group of environmental pollutants called endocrine disruptors. References by scientists, the media, political entities, and non-governmental organizations to many toxicity studies as "low dose" has led to the belief that exposure levels in these studies are similar to humans, implying that BPA is toxic to humans at current exposures. Through systematic, objective comparison of our current, and a previous compilation of the "low-dose" literature to multiple estimates of human external and internal exposure levels, we found that the "low-dose" moniker describes exposures covering 8-12 orders of magnitude, the majority (91-99% of exposures) being greater than the upper bound of human exposure in the general infant, child and adult U.S. Population. "low dose" is therefore a descriptor without specific meaning regarding human exposure. Where human exposure data are available, for BPA and other environmental chemicals, reference to toxicity study exposures by direct comparison to human exposure would be more informative, more objective, and less susceptible to misunderstanding. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Sarin Exposures in A Cohort of British Military Participants in Human Experimental Research at Porton Down 1945-1987.

    Science.gov (United States)

    Keegan, Thomas J; Carpenter, Lucy M; Brooks, Claire; Langdon, Toby; Venables, Katherine M

    2017-12-15

    The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK's centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken. Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis. In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28-51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present. These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  17. Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

    Science.gov (United States)

    Madas, Balázs G

    2016-07-01

    Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

  18. Whole body exposure to low-dose γ-radiation enhances the antioxidant defense system

    International Nuclear Information System (INIS)

    Pathak, C.M.; Avti, P.K.; Khanduja, K.L.; Sharma, S.C.

    2008-01-01

    It is believed that the extent of cellular damage by low- radiation dose is proportional to the effects observed at high radiation dose as per the Linear-No-Threshold (LNT) hypothesis. However, this notion may not be true at low-dose radiation exposure in the living system. Recent evidence suggest that the living organisms do not respond to ionizing radiations in a linear manner in the low dose range 0.01-0.5Gy and rather restore the homeostasis both in vivo and in vitro by normal physiological mechanisms such as cellular and DNA repair processes, immune reactions, antioxidant defense, adaptive responses, activation of immune functions, stimulation of growth etc. In this study, we have attempted to find the critical radiation dose range and the post irradiation period during which the antioxidant defense systems in the lungs, liver and kidneys remain stimulated in these organs after whole body exposure of the animals to low-dose radiation

  19. Biological effects of low-dose ionizing radiation exposure; Biologische Wirkungen niedriger Dosen ionisierender Strahlung

    Energy Technology Data Exchange (ETDEWEB)

    Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst (comps.)

    2009-07-01

    The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

  20. Subacute Low Dose Nerve Agent Exposure Causes DNA Fragmentation in Guinea Pig Leukocytes

    Science.gov (United States)

    2005-10-01

    1 SUBACUTE LOW DOSE NERVE AGENT EXPOSURE CAUSES DNA FRAGMENTATION IN GUINEA PIG LEUKOCYTES. Jitendra R. Dave1, John R. Moffett1, Sally M...DNA fragmentation in blood leukocytes from guinea pigs by ‘Comet’ assay after exposure to soman at doses ranging from 0.1LD50 to 0.4 LD50, once per...computer. Data obtained for exposure to soman demonstrated significant increases in DNA fragmentation in circulating leukocytes in CWNA treated guinea pigs as

  1. Exposure of luminous marine bacteria to low-dose gamma-radiation.

    Science.gov (United States)

    Kudryasheva, N S; Petrova, A S; Dementyev, D V; Bondar, A A

    2017-04-01

    The study addresses biological effects of low-dose gamma-radiation. Radioactive 137 Cs-containing particles were used as model sources of gamma-radiation. Luminous marine bacterium Photobacterium phosphoreum was used as a bioassay with the bioluminescent intensity as the physiological parameter tested. To investigate the sensitivity of the bacteria to the low-dose gamma-radiation exposure (≤250 mGy), the irradiation conditions were varied as follows: bioluminescence intensity was measured at 5, 10, and 20°С for 175, 100, and 47 h, respectively, at different dose rates (up to 4100 μGy/h). There was no noticeable effect of gamma-radiation at 5 and 10°С, while the 20°С exposure revealed authentic bioluminescence inhibition. The 20°С results of gamma-radiation exposure were compared to those for low-dose alpha- and beta-radiation exposures studied previously under comparable experimental conditions. In contrast to ionizing radiation of alpha and beta types, gamma-emission did not initiate bacterial bioluminescence activation (adaptive response). As with alpha- and beta-radiation, gamma-emission did not demonstrate monotonic dose-effect dependencies; the bioluminescence inhibition efficiency was found to be related to the exposure time, while no dose rate dependence was found. The sequence analysis of 16S ribosomal RNA gene did not reveal a mutagenic effect of low-dose gamma radiation. The exposure time that caused 50% bioluminescence inhibition was suggested as a test parameter for radiotoxicity evaluation under conditions of chronic low-dose gamma irradiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Safety and efficacy of low-dose, subacute exposure of mature ewes to sodium chlorate

    Science.gov (United States)

    The objective was to determine the safety and efficacy of low-dose, subacute exposure of mature ewes to NaClO3 in the drinking water. Twenty-five ewes (BW = 62.5 ± 7.3 kg) were placed indoors in individual pens with ad libitum access to water and feed. After 7 d of adaptation, ewes were assigned ran...

  3. Low-Dose Radiation Exposure and Atherosclerosis in ApoE(-/-) Mice

    NARCIS (Netherlands)

    Mitchel, R. E. J.; Hasu, M.; Bugden, M.; Wyatt, H.; Little, M. P.; Gola, A.; Hildebrandt, G.; Priest, N. D.; Whitman, S. C.

    The hypothesis that single low-dose exposures (0.025-0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE(-/-)). Mice were exposed

  4. What happens at very low levels of radiation exposure ? Are the low dose exposures beneficial ?

    International Nuclear Information System (INIS)

    Deniz, Dalji

    2006-01-01

    . This adaptive response seems to be the manifestation of a protective effect that may reduce risk at very low doses. Current knowledge in molecular biology shows no evidence of a threshold effect for Stochastic Effects. Therefore, any level of radiation may be considered to cause them. Conversely, some studies show that low levels of irradiation are in fact beneficial to the health (Radiation Hormesis). However, in the absence of clear scientific evidence, the regulators adopted a conservative approach and consider all levels of radiation as being potentially damaging to the human body (LNT theory). According to LNT theory; the effects of low doses of ionizing radiation can be estimated by linear extrapolation from effects observed by linear extrapolation from effects observed by high doses. There is not any safe dose because even very low doses of ionizing radiation produce some biological effect. The results of many investigations do not support the LNT theory. Furthermore relationship between environmental radon concentrations and lung cancer even contradict this theory and clearly suggest a hermetic effect -radiation hormesis-. Although data are still incomplete, extensive epidemiological studies have indicated that radiation hormesis is really exist. In this review, contradictory evidence Linear No-Threshold Theory and Radiation Hormesis Effect is discussed

  5. Exposure to low-dose barium by drinking water causes hearing loss in mice.

    Science.gov (United States)

    Ohgami, Nobutaka; Hori, Sohjiro; Ohgami, Kyoko; Tamura, Haruka; Tsuzuki, Toyonori; Ohnuma, Shoko; Kato, Masashi

    2012-10-01

    We continuously ingest barium as a general element by drinking water and foods in our daily life. Exposure to high-dose barium (>100mg/kg/day) has been shown to cause physiological impairments. Direct administration of barium to inner ears by vascular perfusion has been shown to cause physiological impairments in inner ears. However, the toxic influence of oral exposure to low-dose barium on hearing levels has not been clarified in vivo. We analyzed the toxic influence of oral exposure to low-dose barium on hearing levels and inner ears in mice. We orally administered barium at low doses of 0.14 and 1.4 mg/kg/day to wild-type ICR mice by drinking water. The doses are equivalent to and 10-fold higher than the limit level (0.7 mg/l) of WHO health-based guidelines for drinking water, respectively. After 2-week exposure, hearing levels were measured by auditory brain stem responses and inner ears were morphologically analyzed. After 2-month exposure, tissue distribution of barium was measured by inductively coupled plasma mass spectrometry. Low-dose barium in drinking water caused severe hearing loss in mice. Inner ears including inner and outer hair cells, stria vascularis and spiral ganglion neurons showed severe degeneration. The Barium-administered group showed significantly higher levels of barium in inner ears than those in the control group, while barium levels in bone did not show a significant difference between the two groups. Barium levels in other tissues including the cerebrum, cerebellum, heart, liver and kidney were undetectably low in both groups. Our results demonstrate for the first time that low-dose barium administered by drinking water specifically distributes to inner ears resulting in severe ototoxicity with degeneration of inner ears in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Data integration reveals key homeostatic mechanisms following low dose radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, Susan C.; Matzke, Melissa M. [Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, WA 99338 (United States); Sowa, Marianne B.; Stenoien, David L.; Weber, Thomas J. [Health Impacts and Exposure Science, Pacific Northwest National Laboratory, Richland, WA 99338 (United States); Morgan, William F. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99338 (United States); Waters, Katrina M., E-mail: katrina.waters@pnnl.gov [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99338 (United States)

    2015-05-15

    , ROS/RNS and DNA repair pathways detected • Low dose exposure alters metabolites involved in nitric oxide biosynthesis and wound healing. • Computationally predicted regulators of primary mechanisms were experimentally validated.

  7. Occupational radiation exposure to low doses of ionizing radiation and female breast cancer

    International Nuclear Information System (INIS)

    Adelina, P.; Bliznakov, V.; Bairacova, A.

    2003-01-01

    The aim of this study is to examine the relationship between past occupational radiation exposure to low doses of ionizing radiation and cases of diagnosed and registered breast cancer [probability of causation - PC] among Bulgarian women who have used different ionizing radiation sources during their working experience. The National Institute of Health (NIH) in US has developed a method for estimating the probability of causation (PC) between past occupational radiation exposure to low doses of ionizing radiation and cases of diagnosed cancer. We have used this method. A group of 27 women with diagnosed breast cancer has been studied. 11 of them are former workers in NPP - 'Kozloduy', and 16 are from other sites using different sources of ionizing radiation. Analysis was performed for 14 women, for whom full personal data were available. The individual radiation dose for each of them is below 1/10 of the annual dose limit, and the highest cumulative dose for a period of 14 years of occupational exposure is 50,21 mSv. The probability of causation (PC) values in all analyzed cases are below 1%, which confirms the extremely low probability of causation (PC) between past occupational radiation exposure to low doses of ionizing radiation and occurring cases of breast cancer. (orig.)

  8. Hormesis of Low Doses of Ionizing Radiation Exposure on Immune System

    International Nuclear Information System (INIS)

    Ragab, M.H.; Abbas, M.O.; El-Asady, R.S.; Amer, H.A.; El-Khouly, W.A.; Shabon, M.H.

    2015-01-01

    The effect of low doses of ionizing radiation on the immune system has been a controversial subject. To evaluate the effect of low-doses γ-irradiation exposure on immune system. An animal model, using Rattus Rattus rats was used. The rats were divided into groups exposed to either continuous or fractionated 100, 200, 300, 400 and 500 mSv of radiation and compared to control rats that did not receive radiation. All groups were exposed to a total white blood count (Wcs), lymphocyte count and serum IgG level measurement, as indicators of the function of the cell-mediated (T lymphocytes) and the humoral (B lymphocytes) immune system. The results of the current study revealed that the counts of total leukocytes (WBCs) and lymphocytes, as well as the serum level of IgG were increased significantly in rats receiving low dose radiation, indicating enhancement of immune system. The data suggests that low-dose gamma-radiation improved hematological parameters and significantly enhances immune response indices of the exposed rats. These findings are similar to the radiation adaptive responses in which a small dose of pre irradiation would induce certain radiation resistance and enhances the cell response after exposure to further irradiation doses The applied low doses used in the present study may appear effective inducing the radio adaptive response. Farooqi and Kesavan (1993) and Bravard et al. (1999) reported that the adaptive response to ionizing radiation refers to the phenomenon by which cells irradiated with low (cGy) or sublethal doses (conditioning doses) become less susceptible to genotoxic effects of a subsequent high dose (challenge dose, several Gy).

  9. Chronic low dose radiation exposure and oxidative stress in radiation workers

    International Nuclear Information System (INIS)

    Ali, S.S.; Bhatt, M.B.; Kulkarni, MM.; Rajan, R.; Singh, B.B.; Venkataraman, G.

    1996-01-01

    Free radicals have been implicated in the pathogenesis of several human diseases. In this study free radical stress due to low dose chronic radiation exposures of radiation workers was examined as a possible atherogenic risk factor. Data on lipid profiles, lipid peroxidation and reduced glutathione content in blood indicated an absence of correlation with radiation doses up to 125 mSv. (author). 13 refs., 1 fig

  10. Operator dependency of the radiation exposure in cardiac interventions: feasibility of ultra low dose levels

    International Nuclear Information System (INIS)

    Emre Ozpelit, Mehmet; Ercan, Ertugrul; Pekel, Nihat; Tengiz, Istemihan; Yilmaz, Akar; Ozpelit, Ebru; Ozyurtlu, Ferhat

    2017-01-01

    Introduction: Mean radiation exposure in invasive cardiology varies greatly between different centres and interventionists. The International Commission on Radiological Protection and the EURATOM Council stipulate that, despite reference values, 'All medical exposure for radiodiagnostic purposes shall be kept as low as reasonably achievable' (ALARA). The purpose of this study is to establish the effects of the routine application of ALARA principles and to determine operator and procedure impact on radiation exposure in interventional cardiology. Materials and methods: A total of 240 consecutive cardiac interventional procedures were analysed. Five operators performed the procedures, two of whom were working in accordance with ALARA principles (Group 1 operators) with the remaining three working in a standard manner (Group 2 operators). Radiation exposure levels of these two groups were compared. Results: Total fluoroscopy time and the number of radiographic runs were similar between groups. However, dose area product and cumulative dose were significantly lower in Group 1 when compared with Group 2. Radiation levels of Group 1 were far below even the reference levels in the literature, thus representing an ultra-low-dose radiation exposure in interventional cardiology. Conclusion: By use of simple radiation reducing techniques, ultra-low-dose radiation exposure is feasible in interventional cardiology. Achievability of such levels depends greatly on operator awareness, desire, knowledge and experience of radiation protection. (authors)

  11. Low-dose CT of the paranasal sinuses. Minimizing X-ray exposure with spectral shaping

    Energy Technology Data Exchange (ETDEWEB)

    Wuest, Wolfgang [Friedrich-Alexander-University Erlangen-Nuremberg, Radiological Institute, Erlangen (Germany); Radiological Institute, Erlangen (Germany); May, Matthias; Saake, Marc; Brand, Michael; Uder, Michael; Lell, Michael [Friedrich-Alexander-University Erlangen-Nuremberg, Radiological Institute, Erlangen (Germany)

    2016-11-15

    Shaping the energy spectrum of the X-ray beam has been shown to be beneficial in low-dose CT. This study's aim was to investigate dose and image quality of tin filtration at 100 kV for pre-operative planning in low-dose paranasal CT imaging in a large patient cohort. In a prospective trial, 129 patients were included. 64 patients were randomly assigned to the study protocol (100 kV with additional tin filtration, 150mAs, 192 x 0.6-mm slice collimation) and 65 patients to the standard low-dose protocol (100 kV, 50mAs, 128 x 0.6-mm slice collimation). To assess the image quality, subjective parameters were evaluated using a five-point scale. This scale was applied on overall image quality and contour delineation of critical anatomical structures. All scans were of diagnostic image quality. Bony structures were of good diagnostic image quality in both groups, soft tissues were of sufficient diagnostic image quality in the study group because of a high level of noise. Radiation exposure was very low in both groups, but significantly lower in the study group (CTDI{sub vol} 1.2 mGy vs. 4.4 mGy, p < 0.001). Spectral optimization (tin filtration at 100 kV) allows for visualization of the paranasal sinus with sufficient image quality at a very low radiation exposure. (orig.)

  12. Quantitative determination of circulating endothelial cells in persons with low dose radioactivity exposure

    International Nuclear Information System (INIS)

    Al-Massarani, Gh.; Najjar, F.

    2013-04-01

    The aim of this study was to determine the risk of occupational exposure to low doses of ionizing radiation on the endothelium detachment through the quantification of circulating endothelial cells (CEC) in the peripheral blood of 63 workers in the Atomic Energy Commission in Syria (AECS) using a Magnetic Immuno-separation technique (IMS) and compare the results with 28 healthy (controls) is not exposed during their careers for any type of ionizing radiation. Our study showed for the first time the significantly increasing in the circulating endothelial cells count (P <0.0001) when employees are exposed to low doses of radiation less than 50 mSv. This result with previous studies about the late effects of radiation, assuming the existence of impact late radiation exposure on the cohesion of the endothelium, despite the lack of correlation with radiation dose measured during the past four years of work in AECS (between 2006-2010). This is due to several reasons, including the small sample size and lack of commitment by some workers develop individual control films during some periods of their work. The prospective studies for such workers can allow us to know if the rise in the number of CEC will be considered an early indicator for the risk of a cardiovascular disease when workers exposed to low-doses of ionizing radiation( tens of millisievert) that up to date are considered harmless (author).

  13. Cytogenetic damage at low doses and the problem of bioindication of chronic low level radiation exposure

    International Nuclear Information System (INIS)

    Geras'kin, S.A.; Dikarev, V.G.; Nesterov, E.B.; Vasiliev, D.V.; Dikareva, N.S.

    2000-01-01

    The analysis undertaken by us of the experimentally observed cellular responses to low dose irradiation has shown that the relationship between the yield of induced cytogenetic damage and radiation dose within low dose range is non-linear and universal in character. Because of the relationship between the yield of cytogenetic damage and dose within low dose range is non-linear, the aberration frequency cannot be used in biological dosimetry in the most important in terms of practical application case. The cytogenetic damage frequency cannot be used in biological dosimetry also because of the probability of synergistic and antagonistic interaction effects of the different nature factors simultaneously acting on test-object in real conditions is high within low dose (concentration) range. In our experimental study of the regularities in the yield of structural mutations in conditions of combined influence of ionizing radiation, heavy metals and pesticides it was found that synergistic and antagonistic effects are mainly induced in conditions of combined action of low exposure injuring agents. Experiments on agricultural plants were carried out in 1986-1989 at the 30-km zone around Chernobyl NPP. It was shown that chronic low dose exposure could cause an inheritable destabilization of genetic structures expressing in increase of cytogenetic damage and yield karyotypic variability in offspring's of irradiated organisms. Obviously exactly this circumstance is the reason of the phenomenon found in our researches of significant time delay of cytogenetic damage reduction rate from radioactive pollution reduction rate from time past from the accident moment. Research of cytogenetic damage of reproductive (seeds) and vegetative (needles) plant organs of the Pinus sylvestris tree micropopulations growing in contrast by radioactive pollution level sites of the 30-km ChNPP zone and also in the vicinity of the industrial plant > for processing and temporary storage of

  14. Effects of low-level sarin and cyclosarin exposure on hippocampal subfields in Gulf War Veterans.

    Science.gov (United States)

    Chao, Linda L; Kriger, Stephen; Buckley, Shannon; Ng, Peter; Mueller, Susanne G

    2014-09-01

    More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Gulf War (GW). We previously reported reduced hippocampal volume in GW veterans with suspected GB/GF exposure relative to matched, unexposed GW veterans estimated from 1.5T magnetic resonance images (MRI). Here we investigate, in a different cohort of GW veterans, whether low-level GB/GF exposure is associated with structural alterations in specific hippocampal subfields, estimated from 4T MRI. The Automatic Segmentation of Hippocampal Subfields (ASHS) technique was used to quantify CA1, CA2, CA3 and dentate gyrus (DG), and subiculum (SUB) subfields volumes from high-resolution T2-weighted images acquired on a 4T MR scanner in 56 GW veterans with suspected GB/GF exposure and 56 "matched" unexposed GW veterans (mean age 49±7 years). GB/GF exposed veterans had smaller CA2 (p=0.003) and CA3/DG (p=0.01) subfield volumes compared to matched, unexposed GW veterans. There were no group difference in total hippocampal volume, quantified with FreeSurfer, and no dose-response relationship between estimated levels of GB/GF exposure and total hippocampal or subfield volume. These findings extend our previous report of structural alterations in the hippocampi of GW veterans with suspected GB/GF exposure to volume changes in the CA2, CA3, and DG hippocampal subfields in a different cohort of GW veterans with suspected GB/GF exposure. Published by Elsevier B.V.

  15. Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans.

    Science.gov (United States)

    Chao, Linda L; Zhang, Yu

    2018-05-04

    In early March 1991, shortly after the end of the Gulf War (GW), a munitions dump was destroyed at Khamisiyah, Iraq. Later, in 1996, the dump was found to have contained the organophosphorus (OP) nerve agents sarin and cyclosarin. We previously reported evidence of smaller hippocampal volumes in GW veterans with predicted exposure to the Khamisiyah plume compared to unexposed GW veterans. To investigate whether these macroscopic hippocampal volume changes are accompanied by microstructural alterations in the hippocampus, the current study acquired diffusion-tensor imaging (DTI), T1-, and T2-weighted images from 170 GW veterans (mean age: 53 ± 7 years), 81 of whom had predicted exposure to the Khamisiyah plume according to Department of Defense (DOD) plume modeling. We examined fractional anisotropy (FA), mean diffusivity (MD), and grey matter (GM) density from a hippocampal region of interest (ROI). Results indicate that, even after accounting for total hippocampal GM density (or hippocampal volume), age, sex, apolipoprotein ε4 genotype, and potential confounding OP pesticide exposures, hippocampal MD significantly predicted Khamisiyah exposure status (model p = 0.005, R 2  = 0.215, standardized coefficient β = 0.26, t = 2.85). Hippocampal MD was also inversely correlated with verbal memory learning performance in the entire study sample (p = 0.001). There were no differences in hippocampal FA or GM density; however, veterans with predicted Khamisiyah exposure had smaller hippocampal volumes compared to unexposed veterans. Because MD is sensitive to general microstructural disruptions that lead to increased extracellular spaces due to neuronal death, inflammation and gliosis, and/or to axonal loss or demyelination, these findings suggest that low-level exposure to the Khamisiyah plume has a detrimental, lasting effects on both macro- and micro-structure of the hippocampus. Copyright © 2018. Published by Elsevier Inc.

  16. Assessment of Subchronic Neurobehaviorial and Neuropathologic Effects in Rats Following Low-Level Sarin Exposure

    National Research Council Canada - National Science Library

    Olson, Carl

    1999-01-01

    .... Doses of pyridostigmine bromide (PB) i.m., Sarin (GB) s.c., and chlorpyrifos (CPF) topically which produced approximately 20-30, 5-10, and 5-10 percent whole blood cholinesterase inhibition (ChE...

  17. Estimates of Health Detriments and Tissue Weighting Factors for Hong Kong Populations from Low Dose, Low Dose Rate and Low LET Ionising Radiation Exposure

    International Nuclear Information System (INIS)

    Lee, S.K.

    1998-01-01

    The total health detriments and the tissue weighting factors for the Hong Kong populations from low dose, low dose rate and low LET ionising radiation exposure are obtained according to the methodology recommended in ICRP Publication 60. The probabilities of fatal cancers for the general (ages 0-90) and working (ages 20-64) populations due to lifetime exposure at low dose and low dose rate are 4.9 x 10 -2 Sv -1 and 3.6 x 10 -2 Sv -1 respectively, comparing with the ICRP 60 estimates of 5.0 x 10 -2 Sv -1 and 4.0 x 10 -2 Sv -1 . The corresponding total health detriments for the general and working populations are 6.9 x 10 -2 Sv -1 and 4.9 x 10 -2 Sv -1 respectively comparing with the ICRP 60 estimates of 7.3 x 10 -2 Sv -1 and 5.6 x 10 -2 Sv -1 . Tissue weighting factors for the general population are 0.01 (bone surface and skin), 0.02 (liver, oesophagus and thyroid), 0.04 (bladder and breast), 0.08 (remainder), 0.10 (stomach), 0.11 (bone marrow), 0.15 (colon), 0.19 (lung) and 0.21 (gonads) and for the working population are 0.01 (bone surface and skin), 0.03 (liver, oesophagus and thyroid), 0.04 (breast), 0.06 (remainder), 0.07 (bladder), 0.08 (colon), 0.14 (bone marrow and stomach), 0.16 (lung) and 0.20 (gonads). (author)

  18. A review of the bystander effect and its implications for low-dose exposure

    International Nuclear Information System (INIS)

    Prise, K.M.; Folkard, M.; Michael, B.D.

    2003-01-01

    Current models for the interaction between ionising radiation and living cells or tissues are based on direct genetic damage produced by energy deposition in cellular DNA. An important observation which has questioned this basic assumption is radiation-induced bystander response, in which cells which have not been directly targeted respond if their neighbours have been exposed. This response predominates at low doses of relevance to radiation risk analysis (<0.2 Gy) and therefore needs to be fully characterised. The development of microbeams, which allow individual cells within populations to be targeted with precise doses of radiation, has provided a useful tool for quantifying this response. The authors' studies have targeted individual human and mouse cells with counted protons and helium ions and monitored neighbouring cells for the production of bystander responses. Bystander responses have been measured after exposures as low as a single proton or helium ion delivered to an individual cell. An important aspect is that these responses saturate with increasing dose to the single target cell, thus the relative roles of direct and indirect (non-targeted) responses change with dose. Studies with multicellular, tissue-based models are providing evidence that bystander responses may have a complex phenotype involving multiple pathways and the overall response may be a balance between multiple signalling processes and responses to radiation exposure. Current models for radiation risk assume a linear non-threshold response and have generally been extrapolated from high-dose exposures. The involvement of competing processes at low doses may have important consequences for understanding the effects of low-dose exposure. (author)

  19. Estimation of radiation exposure from lung cancer screening program with low-dose computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Su Yeon; Jun, Jae Kwan [Graduate School of Cancer Science and Policy, National Cancer Center, Seoul (Korea, Republic of)

    2016-12-15

    The National Lung Screening Trial (NLST) demonstrated that screening with Low-dose Computed Tomography (LDCT) screening reduced lung cancer mortality in a high-risk population. Recently, the United States Preventive Services Task Force (USPSTF) gave a B recommendation for annual LDCT screening for individuals at high-risk. With the promising results, Korea developed lung cancer screening guideline and is planning a pilot study for implementation of national lung cancer screening. With widespread adoption of lung cancer screening with LDCT, there are concerns about harms of screening, including high false-positive rates and radiation exposure. Over the 3 rounds of screening in the NLST, 96.4% of positive results were false-positives. Although the initial screening is performed at low dose, subsequent diagnostic examinations following positive results additively contribute to patient's lifetime exposure. As with implementing a large-scale screening program, there is a lack of established risk assessment about the effect of radiation exposure from long-term screening program. Thus, the purpose of this study was to estimate cumulative radiation exposure of annual LDCT lung cancer screening program over 20-year period.

  20. Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure.

    Science.gov (United States)

    Camarata, Andrew S; Switchenko, Jeffrey M; Demidenko, Eugene; Flood, Ann B; Swartz, Harold M; Ali, Arif N

    2016-04-01

    Current radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose-rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy min. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for the low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures.

  1. The special cell effects and somatic consequences of exposure to low dose radiation

    International Nuclear Information System (INIS)

    Regina Fedortseva; Sergei Aleksanin; Eugene Zheleznyakov; Irina Bychkovskaya

    2007-01-01

    Complete text of publication follows. Objective: The experimental data presented in the report put some clarity into the ongoing polemics about possibility of induction of harmful non-carcinogenic effects in human body as a result of exposure to low doses of radiation. The denial of this possibility is based on the fact that traditionally studied genotoxic effects cannot be the cause of this pathology: the incidence of these effects in exposure to low doses of radiation is fairly low; the effects are not overt in critical slowly regenerating tissues, since they can only be morphologically manifested in actively growing cell populations. Methods: Endothelium of myocardial and alveolar capillaries were studied ultra-structurally in 236 rats irradiated by a wide range of X-ray doses (0,25;0,5;2,25;4,5;9;30;48;100) and 28 intact control animals. Studies were conducted during 12-18 months. The material consisted of 2-3 portions from various parts of myocardium and lung. From each portion, sections were prepared, in which all capillary sections were analyzed and ultra-structure of all lining capillary endotheliocytes (their number most often was more than 100) was studied. In each animal the percentage of non-viable endotheliocytes with signs of generalized organoid destruction, damage of plasmalemma and nuclear structures was accounted. Results: Irradiation of rat to low and higher doses caused significant (up to 7 times) increase number of endothelial cells with various ultra-structural damages (from relatively light ones to in the cell death). Even the lowest dose - 0,25 Gy produce an increasing degeneration, intracellular lysis and defects of mitochondria. We found unusual features of postradiational endothelium changes: dose independence, necessity of revealing the long-term, non-mutational cellular effects, massive involvement of cells, early development of the maximum effect already after the low dose irradiation. These special somatic effects, unlike genotoxic

  2. Long term neurocognitive impact of low dose prenatal methylmercury exposure in Hong Kong.

    Science.gov (United States)

    Lam, Hugh Simon; Kwok, Ka Ming; Chan, Peggy Hiu Ying; So, Hung Kwan; Li, Albert Martin; Ng, Pak Cheung; Fok, Tai Fai

    2013-04-01

    International studies suggest that low dose prenatal methylmercury exposure (>29 nmol/L) has long-term adverse neurocognitive effects. There is evidence that the majority of children in Hong Kong exceed this level as a result of high fish consumption of mothers during pregnancy. To study whether there are any associations between low-dose prenatal methylmercury exposure and neurocognitive outcomes in Hong Kong children. All 1057 children from the original birth cohort were eligible for entry into the study, except children with conditions that would affect neurocognitive development, but were unrelated to methylmercury exposure. Subjects were assessed by a wide panel of tests covering a broad range of neurocognitive functions: Hong Kong Wechsler Intelligence Scale for Children (HK-WISC), Hong Kong List Learning Test (HKLLT), Tests of Everyday Attention for Children (TEACH), Boston Naming Test, and Grooved Pegboard Test. 608 subjects were recruited (median age 8.2 years, IQR 7.3, 8.8; 53.9% boys). After correction by confounders including child age and sex, multivariate analysis showed that cord blood mercury concentration was significantly associated with three subtests: Picture Arrangement of HK-WISC (coefficient -0.944, P=0.049) and Short and Long Delay Recall Difference of the HKLLT (coefficient -1.087, P=0.007 and coefficient -1.161, P=0.005, respectively), i.e., performance worsened with increasing prenatal methylmercury exposure in these subtests. Small, but statistically significant adverse associations between prenatal methylmercury exposure and long-term neurocognitive effects (a visual sequencing task and retention ability of verbal memory) were found in our study. These effects are compatible with findings of studies with higher prenatal methylmercury exposure levels and suggest that safe strategies to further reduce exposure levels in Hong Kong are desirable. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Single whole-body exposure to sarin vapor in rats: Long-term neuronal and behavioral deficits

    International Nuclear Information System (INIS)

    Grauer, Ettie; Chapman, Shira; Rabinovitz, Ishai; Raveh, Lily; Weissman, Ben-Avi; Kadar, Tamar; Allon, Nahum

    2008-01-01

    Freely moving rats were exposed to sarin vapor (34.2 ± 0.8 μg/l) for 10 min. Mortality at 24 h was 35% and toxic sings in the surviving rats ranged from sever (prolonged convulsions) through moderate to almost no overt signs. Some of the surviving rats developed delayed, intermittent convulsions. All rats were evaluated for long-term functional deficits in comparison to air-exposed control rats. Histological analysis revealed typical cell loss at 1 week post inhalation exposure. Neuronal inflammation was demonstrated by a 20-fold increase in prostaglandin (PGE 2 ) levels 24 h following exposure that markedly decreased 6 days later. An additional, delayed increase in PGE 2 was detected at 1 month and continued to increase for up to 6 months post exposure. Glial activation following neural damage was demonstrated by an elevated level of peripheral benzodiazepine receptors (PBR) seen in the brain 4 and 6 months after exposure. At the same time muscarinic receptors were unaffected. Six weeks, four and six months post exposure behavioral evaluations were performed. In the open field, sarin-exposed rats showed a significant increase in overall activity with no habituation over days. In a working memory paradigm in the water maze, these same rats showed impaired working and reference memory processes with no recovery. Our data suggest long lasting impairment of brain functions in surviving rats following a single sarin exposure. Animals that seem to fully recover from the exposure, and even animals that initially show no toxicity signs, developed some adverse neural changes with time

  4. Low-dose cadmium exposure exacerbates polyhexamethylene guanidine-induced lung fibrosis in mice.

    Science.gov (United States)

    Kim, Min-Seok; Kim, Sung-Hwan; Jeon, Doin; Kim, Hyeon-Young; Han, Jin-Young; Kim, Bumseok; Lee, Kyuhong

    2018-01-01

    Cadmium (Cd) is a toxic metal present in tobacco smoke, air, food, and water. Inhalation is an important route of Cd exposure, and lungs are one of the main target organs for metal-induced toxicity. Cd inhalation is associated with an increased risk of pulmonary diseases. The present study aimed to assess the effects of repeated exposure to low-dose Cd in a mouse model of polyhexamethylene guanidine (PHMG)-induced lung fibrosis. Mice were grouped into the following groups: vehicle control (VC), PHMG, cadmium chloride (CdCl 2 ), and PHMG + CdCl 2 . Animals in the PHMG group exhibited increased numbers of total cells and inflammatory cells in the bronchoalveolar lavage fluid (BALF) accompanied by inflammation and fibrosis in lung tissues. These parameters were exacerbated in mice in the PHMG + CdCl 2 group. In contrast, mice in the CdCl 2 group alone displayed only minimal inflammation in pulmonary tissue. Expression of inflammatory cytokines and fibrogenic mediators was significantly elevated in lungs of mice in the PHMG group compared with that VC. Further, expression of these cytokines and mediators was enhanced in pulmonary tissue in mice administered PHMG + CdCl 2 . Data demonstrate that repeated exposure to low-dose Cd may enhance the development of PHMG-induced pulmonary fibrosis.

  5. Exposure to Low-Dose X-Ray Radiation Alters Bone Progenitor Cells and Bone Microarchitecture.

    Science.gov (United States)

    Lima, Florence; Swift, Joshua M; Greene, Elisabeth S; Allen, Matthew R; Cunningham, David A; Braby, Leslie A; Bloomfield, Susan A

    2017-10-01

    Exposure to high-dose ionizing radiation during medical treatment exerts well-documented deleterious effects on bone health, reducing bone density and contributing to bone growth retardation in young patients and spontaneous fracture in postmenopausal women. However, the majority of human radiation exposures occur in a much lower dose range than that used in the radiation oncology clinic. Furthermore, very few studies have examined the effects of low-dose ionizing radiation on bone integrity and results have been inconsistent. In this study, mice were irradiated with a total-body dose of 0.17, 0.5 or 1 Gy to quantify the early (day 3 postirradiation) and delayed (day 21 postirradiation) effects of radiation on bone microarchitecture and bone marrow stromal cells (BMSCs). Female BALBc mice (4 months old) were divided into four groups: irradiated (0.17, 0.5 and 1 Gy) and sham-irradiated controls (0 Gy). Micro-computed tomography analysis of distal femur trabecular bone from animals at day 21 after exposure to 1 Gy of X-ray radiation revealed a 21% smaller bone volume (BV/TV), 22% decrease in trabecular numbers (Tb.N) and 9% greater trabecular separation (Tb.Sp) compared to sham-irradiated controls (P X-rays, whereas osteoclastogenesis was enhanced. A better understanding of the effects of radiation on osteoprogenitor cell populations could lead to more effective therapeutic interventions that protect bone integrity for individuals exposed to low-dose ionizing radiation.

  6. Consequences of low dose ionizing radiation exposure on the hippocampal microenvironment.

    Directory of Open Access Journals (Sweden)

    Munjal M Acharya

    Full Text Available The response of the brain to irradiation is complex, involving a multitude of stress inducible pathways that regulate neurotransmission within a dynamic microenvironment. While significant past work has detailed the consequences of CNS radiotherapy following relatively high doses (≥ 45 Gy, few studies have been conducted at much lower doses (≤ 2 Gy, where the response of the CNS (like many other tissues may differ substantially from that expected from linear extrapolations of high dose data. Low dose exposure could elicit radioadaptive modulation of critical CNS processes such as neurogenesis, that provide cellular input into hippocampal circuits known to impact learning and memory. Here we show that mice deficient for chemokine signaling through genetic disruption of the CCR2 receptor exhibit a neuroprotective phenotype. Compared to wild type (WT animals, CCR2 deficiency spared reductions in hippocampal neural progenitor cell survival and stabilized neurogenesis following exposure to low dose irradiation. While radiation-induced changes in microglia levels were not found in WT or CCR2 deficient animals, the number of Iba1+ cells did differ between each genotype at the higher dosing paradigms, suggesting that blockade of this signaling axis could moderate the neuroinflammatory response. Interestingly, changes in proinflammatory gene expression were limited in WT animals, while irradiation caused significant elevations in these markers that were attenuated significantly after radioadaptive dosing paradigms in CCR2 deficient mice. These data point to the importance of chemokine signaling under low dose paradigms, findings of potential significance to those exposed to ionizing radiation under a variety of occupational and/or medical scenarios.

  7. Environmental exposure to low-doses of ionizing radiation. Effects on early nephrotoxicity in mice.

    Science.gov (United States)

    Bellés, Montserrat; Gonzalo, Sergio; Serra, Noemí; Esplugas, Roser; Arenas, Meritxell; Domingo, José Luis; Linares, Victoria

    2017-07-01

    Nuclear accidents of tremendous magnitude, such as those of Chernobyl (1986) and Fukushima (2011), mean that individuals living in the contaminated areas are potentially exposed to ionizing radiation (IR). However, the dose-response relationship for effects of low doses of radiation is not still established. The present study was aimed at investigating in mice the early effects of low-dose internal radiation exposure on the kidney. Adult male (C57BL/6J) mice were divided into three groups. Two groups received a single subcutaneous (s.c.) doses of cesium ( 137 Cs) with activities of 4000 and 8000Bq/kg bw. A third group (control group) received a single s.c. injection of 0.9% saline. To evaluate acute and subacute effects, mice (one-half of each group) were euthanized at 72h and 10 days post-exposure to 137 Cs, respectively. Urine samples were collected for biochemical analysis, including the measurement of F2-isoprostane (F2-IsoP) and kidney injury molecule-1 (KIM-1) levels. Moreover, the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA damage, were measured in renal tissue. Urinary excretion of total protein significantly increased at 72h in mice exposed to Cs4000. Uric acid and lactate dehydrogenase (LDH) decreased significantly at both times post-exposure in animals exposed to Cs8000. After 72h and 10d of exposure to Cs4000, a significant increase in the γ-glutamil transferase (GGT) and N-acetyl-β-D-glucosaminidase (NAG) activities was observed. In turn, F2-IsoP levels increased -mainly in the Cs4000 group- at 72h post-exposure. Following irradiation ( 137 Cs), the highest level of KIM-1 was corresponded to the Cs4000 group at 72h. Likewise, the main DNA damage was detected in mice exposed to Cs4000, mainly at 10d after irradiation. The alterations observed in several biomarkers suggest an immediate renal damage following exposure to low doses of IR (given as 137 Cs). Further investigations are required to clarify the

  8. Causes of genome instability: the effect of low dose chemical exposures in modern society

    Science.gov (United States)

    Langie, Sabine A.S.; Koppen, Gudrun; Desaulniers, Daniel; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Azqueta, Amaya; Bisson, William H.; Brown, Dustin; Brunborg, Gunnar; Charles, Amelia K.; Chen, Tao; Colacci, Annamaria; Darroudi, Firouz; Forte, Stefano; Gonzalez, Laetitia; Hamid, Roslida A.; Knudsen, Lisbeth E.; Leyns, Luc; Lopez de Cerain Salsamendi, Adela; Memeo, Lorenzo; Mondello, Chiara; Mothersill, Carmel; Olsen, Ann-Karin; Pavanello, Sofia; Raju, Jayadev; Rojas, Emilio; Roy, Rabindra; Ryan, Elizabeth; Ostrosky-Wegman, Patricia; Salem, Hosni K.; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Van Schooten, Frederik J.; Valverde, Mahara; Woodrick, Jordan; Zhang, Luoping; van Larebeke, Nik; Kirsch-Volders, Micheline; Collins, Andrew R.

    2015-01-01

    Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome’s integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis. PMID:26106144

  9. Lifetime exposure to low doses of lead in rats: effect on selected parameters of carbohydrate metabolism.

    Science.gov (United States)

    Nováková, Jaroslava; Lukačínová, Agnesa; Lovásová, Eva; Cimboláková, Iveta; Rácz, Oliver; Ništiar, František

    2015-05-01

    The aim of the study was to assess the effects of exposure to low doses of lead dissolved in drinking water (average daily dose of 2.2 mg kg(-1) day(-1)) on selected carbohydrate metabolism parameters in 20 wistar rats. Animals were divided into two groups - control (C) (group drinking clear water) and experimental group (Pb; group exposed to low doses of lead acetate in a concentration of 100 μmol l(-1) of drinking water). In this study, we studied the biochemical parameters (glucose, haemoglobin (Hb), glycated haemoglobin (HbA1c), lactate dehydrogenase (LDH) and amylase (AMS)) in rat blood. Glucose and Hb concentration and AMS activity decreased, LDH activity increased but HbA1c concentration levels did not change in rats exposed to lead. Our results well documented that lifetime exposure to lead affected carbohydrate metabolism of rats. Some parameters like concentration of Hb as well as activities of AMS and LDH are useful markers of intoxication of rats with lead. For the evaluation of results (e.g. AMS), not only the data at the end of the experiment should be taken into account but also the entire duration of trials (i.e. more time steps) that makes results more objective should be considered. © The Author(s) 2013.

  10. Consequences of the exposure at low dose rates-contribution of animal experimentation

    International Nuclear Information System (INIS)

    Masse, R.

    1990-01-01

    The exposure of laboratory animals to the various types of radiations will induce cancers in relation with the tissue absorbed doses. The shape of the dose-effet relationship is most variable. It is important to distinguish which tumours are comparable to human tumours. Those showing more analogies answer but seldom to the classical lineo-quadratic relationship; however, a strong attenuation of induction is demonstrated at low dose rates. Quasi-threshold relationships are seen after the exposure of some tissues to high-LET radiations. These observations question the validity of generalizing the radiobiologists' dual action theory, setting the origin of the dose-effect relationship in the induction of events within the DNA molecule. There is an alternative in the cellular collaboration events; it assumes that the effectiveness per dose unit decreases constantly as an inverse function of the dose rate [fr

  11. Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans.

    Science.gov (United States)

    Chao, Linda L; Rothlind, Johannes C; Cardenas, Valerie A; Meyerhoff, Dieter J; Weiner, Michael W

    2010-09-01

    Potentially more than 100,000 US troops may have been exposed to the organophosphate chemical warfare agents sarin (GB) and cyclosarin (GF) when a munitions dump at Khamisiyah, Iraq was destroyed during the Gulf War (GW) in 1991. Although little is known about the long-term neurobehavioral or neurophysiological effects of low-dose exposure to GB/GF in humans, recent studies of GW veterans from the Devens Cohort suggest decrements in certain cognitive domains and atrophy in brain white matter occur individuals with higher estimated levels of presumed GB/GF exposure. The goal of the current study is to determine the generalizability of these findings in another cohort of GW veterans with suspected GB/GF exposure. Neurobehavioral and imaging data collected in a study on Gulf War Illness between 2002 and 2007 were used in this study. We focused on the data of 40 GW-deployed veterans categorized as having been exposed to GB/GF at Khamisiyah, Iraq and 40 matched controls. Magnetic resonance images (MRI) of the brain were analyzed using automated and semi-automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and hippocampus. GW veterans with suspected GB/GF exposure had reduced total GM and hippocampal volumes compared to their unexposed peers (p< or =0.01). Although there were no group differences in measures of cognitive function or total WM volume, there were significant, positive correlations between total WM volume and measures of executive function and visuospatial abilities in veterans with suspected GB/GF exposure. These findings suggest that low-level exposure to GB/GF can have deleterious effects on brain structure and brain function more than decade later. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Low dose perfluorooctanoate exposure promotes cell proliferation in a human non-tumor liver cell line

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hongxia; Cui, Ruina [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Guo, Xuejiang [State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029 (China); Hu, Jiayue [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Dai, Jiayin, E-mail: daijy@ioz.ac.cn [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China)

    2016-08-05

    Highlights: • Differential expression of proteins induced by PFOA in HL-7702 was identified. • Most of the differentially expressed proteins are related to cell proliferation. • A low dose of PFOA stimulates HL-7702 cell proliferation. • A high dose of PFOA inhibits HL-7702 cell proliferation. - Abstract: Perfluorooctanoate (PFOA) is a well-known persistent organic pollutant widely found in the environment, wildlife and humans. Medical surveillance and experimental studies have investigated the potential effects of PFOA on human livers, but the hepatotoxicity of PFOA on humans and its underlying mechanism remain to be clarified. We exposed a human liver cell line (HL-7702) to 50 μM PFOA for 48 h and 96 h, and identified 111 significantly differentially expressed proteins by iTRAQ analysis. A total of 46 proteins were related to cell proliferation and apoptosis. Through further analysis of the cell cycle, apoptosis and their related proteins, we found that low doses of PFOA (50–100 μM) promoted cell proliferation and numbers by promoting cells from the G1 to S phases, whereas high doses of PFOA (200–400 μM) led to reduced HL-7702 cell numbers compared with that of the control mainly due to cell cycle arrest in the G0/G1 phase. To our knowledge, this is the first report on the promotion of cell cycle progression in human cells following PFOA exposure.

  13. Investigations of putative reproductive toxicity of low-dose exposures to vinclozolin in Wistar rats.

    Science.gov (United States)

    Flick, Burkhard; Schneider, Steffen; Melching-Kollmuss, Stephanie; Fussell, Karma C; Gröters, Sibylle; Buesen, Roland; Strauss, Volker; van Ravenzwaay, Bennard

    2017-04-01

    The current investigation examines whether the fungicide vinclozolin, which has an anti-androgenic mode of action, is capable of disrupting endocrine homeostasis at very low doses. The data generated clarify whether a non-monotonic dose-response relationship exists to enhance the current debate about the regulation of endocrine disruptors. Moreover, it is part of a series of investigations assessing the dose-response relationship of single and combined administration of anti-androgenic substances. A pre-postnatal in vivo study design was chosen which was compliant with regulatory testing protocols. The test design was improved by additional endpoints addressing hormone levels, morphology and histopathological examinations. Doses were chosen to represent an effect level (20 mg/kg bw/d), the current NOAEL (4 mg/kg bw/d), and a dose close to the "ADI" (0.005 mg/kg bw/d) for the detection of a possible non-monotonic dose-response curve. Anti-androgenic changes were observable at the effect level but not at lower exposures. Nipple/areola counts appeared to be the most sensitive measure of effect, followed by male sex organ weights at sexual maturation, and finally gross and histopathological findings. The results indicate the absence of evidence for effects at low or very low dose levels. A non-monotonic dose-response relationship was not evident.

  14. Studies on chromosome aberrations induced in human lymphocytes by very low-dose exposure to tritium

    International Nuclear Information System (INIS)

    Hori, T.; Moriya, Junko; Nakai, Sayaka

    1978-01-01

    Assessment of potential hazard from environmental tritium to man becomes very important with increasing the development of nuclear-power industry. However, little data are available as to the determination on the genetic effect of tritium especially at the low levels. The object of the present study is to obtain quantitative data for chromosome aberrations in human lymphocytes, as an indicator for genetic risk estimation, induced by tritium at very low dose levels. Leukocyte cultures of human peripheral blood were chronically exposed for 48h to tritiated water and 3 H-thymidine using a wide range of tritium doses, and aberrations in lymphocyte chromosomes at the first metaphases were examined. In the experimental conditions, the types of aberrations induced by radiation emitted from both tritiated water and 3 H-thymidine were mostly chromatid types, such as chromatid gaps and deletions. The dose-response relations for chromatid breaks per cell exhibited unusual dose-dependency in both cases. It was demonstrated that at higher dose range the yields of chromatid breaks increased linearly with dose, while those at lower dose range were significantly higher than would be expected by a downward extraporation from the linear relation. Partial-hit or partial-target kinetics events appeared at very low dose exposure. (author)

  15. Low dose perfluorooctanoate exposure promotes cell proliferation in a human non-tumor liver cell line

    International Nuclear Information System (INIS)

    Zhang, Hongxia; Cui, Ruina; Guo, Xuejiang; Hu, Jiayue; Dai, Jiayin

    2016-01-01

    Highlights: • Differential expression of proteins induced by PFOA in HL-7702 was identified. • Most of the differentially expressed proteins are related to cell proliferation. • A low dose of PFOA stimulates HL-7702 cell proliferation. • A high dose of PFOA inhibits HL-7702 cell proliferation. - Abstract: Perfluorooctanoate (PFOA) is a well-known persistent organic pollutant widely found in the environment, wildlife and humans. Medical surveillance and experimental studies have investigated the potential effects of PFOA on human livers, but the hepatotoxicity of PFOA on humans and its underlying mechanism remain to be clarified. We exposed a human liver cell line (HL-7702) to 50 μM PFOA for 48 h and 96 h, and identified 111 significantly differentially expressed proteins by iTRAQ analysis. A total of 46 proteins were related to cell proliferation and apoptosis. Through further analysis of the cell cycle, apoptosis and their related proteins, we found that low doses of PFOA (50–100 μM) promoted cell proliferation and numbers by promoting cells from the G1 to S phases, whereas high doses of PFOA (200–400 μM) led to reduced HL-7702 cell numbers compared with that of the control mainly due to cell cycle arrest in the G0/G1 phase. To our knowledge, this is the first report on the promotion of cell cycle progression in human cells following PFOA exposure.

  16. Pre- and postnatal exposure to low dose glufosinate ammonium induces autism-like phenotypes in mice.

    Science.gov (United States)

    Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Hébert, Betty; Aguillon-Naury, Marine; Richard, Olivier; Menuet, Arnaud; Mazaud-Guittot, Séverine; Lesné, Laurianne; Briault, Sylvain; Jegou, Bernard; Pichon, Jacques; Montécot-Dubourg, Céline; Mortaud, Stéphane

    2014-01-01

    Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 - two genes implicated in autism-like deficits - was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.

  17. Perinatal exposure to low dose glufosinate ammonium induces autism-like phenotypes in mice.

    Directory of Open Access Journals (Sweden)

    Anthony eLaugeray

    2014-11-01

    Full Text Available Glufosinate ammonium (GLA is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in normalized brain weight of the offspring. In addition, reduced expression of Pten and Peg3 - two genes implicated in autism-like deficits – was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between perinatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.

  18. Cardiovascular effects after low-dose exposure and radiotherapy: what research is needed?

    Energy Technology Data Exchange (ETDEWEB)

    Wondergem, Jan [International Atomic Energy Agency, Applied Radiation Biology and Radiotherapy Section, Division of Human Health, Department of Nuclear Sciences and Applications, Vienna (Austria); Boerma, Marjan [University of Arkansas for Medical Sciences, Division of Radiation Health, Department of Pharmaceutical Sciences, Little Rock, AR (United States); Kodama, Kazunori [Radiation Effects Research Foundation, Hiroshima (Japan); Stewart, Fiona A. [Netherlands Cancer Institute, Biological Stress Response (H3), Amsterdam (Netherlands); Trott, Klaus R.

    2013-11-15

    The authors of this report met at the Head Quarter of the International Atomic Energy Agency (IAEA) in Vienna, Austria, on 2-4 July 2012, for intensive discussions of an abundance of original publications on new epidemiological studies on cardiovascular effects after low-dose exposure and radiotherapy and radiobiological experiments as well as several comprehensive reviews that were published since the previous meeting by experts sponsored by the IAEA in June 2006. The data necessitated a re-evaluation of the situation with special emphasis on the consequences current experimental and clinical data may have for clinical oncology/radiotherapy and radiobiological research. The authors jointly arrived at the conclusions and recommendations presented here. (orig.)

  19. Cardiovascular effects after low-dose exposure and radiotherapy: what research is needed?

    International Nuclear Information System (INIS)

    Wondergem, Jan; Boerma, Marjan; Kodama, Kazunori; Stewart, Fiona A.; Trott, Klaus R.

    2013-01-01

    The authors of this report met at the Head Quarter of the International Atomic Energy Agency (IAEA) in Vienna, Austria, on 2-4 July 2012, for intensive discussions of an abundance of original publications on new epidemiological studies on cardiovascular effects after low-dose exposure and radiotherapy and radiobiological experiments as well as several comprehensive reviews that were published since the previous meeting by experts sponsored by the IAEA in June 2006. The data necessitated a re-evaluation of the situation with special emphasis on the consequences current experimental and clinical data may have for clinical oncology/radiotherapy and radiobiological research. The authors jointly arrived at the conclusions and recommendations presented here. (orig.)

  20. Biochemical Tolerance During Low Dose Propylene Glycol Exposure in Neonates: A Formulation-Controlled Evaluation

    Directory of Open Access Journals (Sweden)

    Aida Kulo

    2012-07-01

    Full Text Available Background and purpose of the study: Propylene glycol (PG is a frequently co-administered solvent in formulations administered to neonates, but reports on its (intolerance are limited. We aimed to report on renal, metabolic and hepatic tolerance before, during and following intravenous (iv PG-paracetamol exposure and compared these data with similar datasets reported in literature on neonates exposed to PG without paracetamol or paracetamol without PG.Methods: Renal (diuresis, creatinemia, sodium, metabolic (Base Excess, Anion Gap, lactate, bicarbonate and hepatic (liver enzymes, bilirubinemia indicators before, during and following iv paracetamol-PG exposure in neonates as included in the PARANEO (paracetamol in neonates study (intra-individual trends, ANOVA were collected and analysed.Comparison with observations collected in cases exposed to either iv phenobarbital-PG or iv paracetamol-mannitol (inter-individual comparison, Mann Whitney-U test were made. Results: PG exposure (median 34.1 mg/kg/24 h did not affect postnatal renal, metabolic and hepatic adaptations in 60 cases exposed to paracetamol-PG. These indicators were similar when compared to 29 cases exposed to phenobarbital- PG or 172 cases exposed to paracetamol-mannitol.Major conclusion: Based on observations in 89 neonates, low dose PG exposure was tolerated well. Studies on PG pharmacokinetics and its covariates are needed to estimate the upper level of PG tolerance in neonates.

  1. Plants ecotoxicology. A case of low doses and multi pollutant exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' Kin, S.; Kim, J.; Evseeva, T.; Oudalova, A.; Dikarev, V. [Russian Institute of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2004-07-01

    In this report, results of long-term laboratory, 'green-house' and field experiments carried out on different species of wild and agricultural plants (spring barley, Scots pine, spider wort, bulb onion and others) to study toxic and genotoxic effects of low doses and concentrations of such common pollutants as acute and chronic {gamma}-radiation, heavy natural radionuclides, compounds of heavy and alkaline earth metals, pesticides are presented for the first time. Special attention is paid to eco-toxic effects of chronic low dose exposures, the dose-rate effect, synergistic and antagonistic effects of different factors' combined exposures and biological effects of incorporated radionuclides. The results of long-term field experiments in the 30-km Chernobyl NPP zone, in the vicinity of the facility for the processing and storage of radioactive wastes (Leningrad region), in the vicinity of the radium production industry storage cell (Komi Republic), at the site of an underground nuclear explosion (Perm region) are discussed. These findings suggest that the further evolution of investigations in this field would issue in the development of a theoretical bases and practical procedures for environmental protection against radioactivity, taking into account the new experimentally confirmed facts about the presence of such essentially important singularities of the biological effect of low ionizing radiation doses as the nonlinearity of a dose-effect relationship, radiation-induced genomic instability, phenomenon of radio-adaptation, increased probability of synergetic and antagonistic effects of the combined action of different nature factors. A development of a new concept of radiation protection for a human and biota should be based on the clear understanding of these effects and their contribution to the response of biological objects. (author)

  2. Low-Dose Ionizing Radiation Exposure, Oxidative Stress and Epigenetic Programing of Health and Disease.

    Science.gov (United States)

    Tharmalingam, Sujeenthar; Sreetharan, Shayenthiran; Kulesza, Adomas V; Boreham, Douglas R; Tai, T C

    2017-10-01

    Ionizing radiation exposure from medical diagnostic imaging has greatly increased over the last few decades. Approximately 80% of patients who undergo medical imaging are exposed to low-dose ionizing radiation (LDIR). Although there is widespread consensus regarding the harmful effects of high doses of radiation, the biological effects of low-linear energy transfer (LET) LDIR is not well understood. LDIR is known to promote oxidative stress, however, these levels may not be large enough to result in genomic mutations. There is emerging evidence that oxidative stress causes heritable modifications via epigenetic mechanisms (DNA methylation, histone modification, noncoding RNA regulation). These epigenetic modifications result in permanent cellular transformations without altering the underlying DNA nucleotide sequence. This review summarizes the major concepts in the field of epigenetics with a focus on the effects of low-LET LDIR (stress on epigenetic gene modification. In this review, we show evidence that suggests that LDIR-induced oxidative stress provides a mechanistic link between LDIR and epigenetic gene regulation. We also discuss the potential implication of LDIR exposure during pregnancy where intrauterine fetal development is highly susceptible to oxidative stress-induced epigenetic programing.

  3. Comparative toxicity of low dose tributyltin chloride on serum, liver, lung and kidney following subchronic exposure.

    Science.gov (United States)

    Mitra, Sumonto; Gera, Ruchi; Singh, Vikas; Khandelwal, Shashi

    2014-02-01

    Tributyltin (TBT) pollution is rampant worldwide and is a growing threat due to its bio-accumulative property. Isolated studies of TBT toxicity on different organs are available but consolidated information is greatly lacking. We planned this study to delineate the effect of subchronic (1 month) exposure to low dose TBT-chloride (TBTC) (1 and 5 mg/kg) in male Wistar rats. Total tin concentration was found to be significantly increased in liver, kidney and blood, and marginally in lungs. Organo-somatic indices were seen to be altered with little effect on serum biochemical markers (liver and kidney function, and general parameters). Reactive oxygen species but not lipid peroxidation content was observed to be significantly elevated both in the tissues and serum. TBTC was found to act as a hyperlipidemic agent and it also affected heme biosynthetic pathway. Hematological analysis showed that TBTC exposure resulted in minor alterations in RBC parameters. Histological studies demonstrated marked tissue damage in all the 3 organs. Calcium inhibitors (BAPTA-AM, EGTA) and antioxidants (NAC, C-PC) significantly restored TBTC induced loss in cell viability, under ex-vivo conditions. Antioxidants were evidently more efficient in comparison to the calcium inhibitors, implying major role of oxidative stress pathways in TBTC toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Perinatal exposure to low doses of tributyltin chloride reduces sperm count and quality in mice.

    Science.gov (United States)

    Si, Jiliang; Li, Peng; Xin, Quanbing; Li, Xuewen; An, Lihong; Li, Jie

    2015-01-01

    Exposure to endocrine disruptors (EDs) during early development might lead to adverse health outcomes later in life. Tributyltin (TBT), a proven ED, is widely used in consumer goods and industrial products. Herein we demonstrate the effects of low doses of tributyltin chloride (TBTCl) on reproduction of male KM mice. Pregnant mice were administered by gavage with 0, 1, 10, or 100 μg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. TBTCl dramatically decreased sperm counts and motility on postnatal days (PNDs) 49 and 152. Meanwhile, a significant increase in sperm abnormality was observed in exposed mice on PND 49, but comparable to that in the control on PND 152. The histopathological analysis of testes of treated animals showed a dose-dependent increase in sloughing of germ cells in seminiferous tubules. Mice treated with 10 μg TBTCl/kg exhibited decreased intratesticular 17β-estradiol (E2) levels on PND 49, and then followed by an obvious recovery on PND 152. While, no significant differences in serum E2, testosterone (T) levels and intratesticular T levels were detectable between control and TBTCl-exposed offspring at the sacrifice. These results suggest that perinatal TBTCl exposure is implicated in causing long lasting alterations in male reproductive system and these changes may persist far into adulthood. © 2013 Wiley Periodicals, Inc.

  5. Deterioration in brain and heart functions following a single sub-lethal (0.8 LCt50) inhalation exposure of rats to sarin vapor:

    International Nuclear Information System (INIS)

    Allon, N.; Chapman, S.; Egoz, I.; Rabinovitz, I.; Kapon, J.; Weissman, B.A.; Yacov, G.; Bloch-Shilderman, E.; Grauer, E.

    2011-01-01

    The main injuries among victims of the terrorist act in the Tokyo subway resulted from sub-lethal inhalation and whole body exposure to sarin vapor. In order to study the long term effects of such exposure and to simulate these conditions, freely moving rats were exposed to sarin vapor (27.2 ± 1.7 μg/l) for 10 min. About 50% of the rats showed no overt symptoms and the rest had mild to moderate clinical symptoms that subsided within 4 h following exposure. A reduction of weight was noted during the first 3 days with full recovery on the 4th day. Rat's heart was challenged with epinephrine 1 and 6 months post exposure. A significant reduction in the threshold for epinephrine-induced arrhythmia (EPIA) was noted in rats exposed to sarin. A time dependent increase in the kD and Bmax values of muscarinic auto receptors (M2) was recorded in the rat's cortex and striatum. No changes were recorded in the rats' brain trans locator protein (TSPO) levels, concomitant with no observed changes in the animals' performance in A Morris water maze test. A significant increase in open field activity was noted 6 months following exposure to sarin vapor as well as a significant decrease in prostaglandin E 2 (PGE 2 ) production in the brain. It is speculated that down regulation of the M2 auto receptor function, caused hyper reactivity of the cholinergic system which leads to the changes described above. The continuous reduction in M2 auto-receptor system through an unknown mechanism may be the cause for long lasting decline in sarin-exposed casualties' health.

  6. Adverse effects on sexual development in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides

    DEFF Research Database (Denmark)

    Hass, Ulla; Boberg, Julie; Christiansen, Sofie

    2012-01-01

    The present study investigated whether a mixture of low doses of five environmentally relevant endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, would cause adverse developmental toxicity effects in rats. In rat dams, a significant increase...... and cumulative intake, because of the potentially serious impact of mixed exposure on development and reproduction in humans....

  7. Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

    International Nuclear Information System (INIS)

    Li Rong; Ai Guoping; Xu Hui; Su Yongping; Cheng Tianmin; Leng Yanbing

    2007-01-01

    Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F 0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg -1 ·d -1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F 0 rats were detected, as well as the survival rate and weight of F 1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F 0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F 1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F 0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F 1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na + -K + -ATPase decreased in F 1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F 0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F 1 generation was observed at any dose. (authors)

  8. Differential stimulation of antioxidant defense in various organs of mice after whole body exposure to low-dose gamma radiation

    International Nuclear Information System (INIS)

    Pathak, C.M.; Avti, P.K.; Khanduja, K.L.; Sharma, S.C.

    2007-01-01

    It has been generally considered that any dose of ionizing radiation is detrimental to the living organisms, however low the radiation dose may be. The much relied upon 'Linear-No-Threshold' (LNT) hypothesis dose not have any convincing experimental evidence regarding the damaging effects at very low-doses and low-dose rates. Generally, the deleterious biological effects have been inferred theoretically by extrapolating the known effects of high radiation dose to low-dose range. Recently, it has been reported that the living organisms do not respond to ionizing radiations in a linear manner in the low-dose range 0.01-0.50 Gy and rather restore the homeostasis both in-vivo and in-vitro by normal physiological mechanisms such as, cellular and DNA repair processes, immune reactions, antioxidant defense, adaptive responses, activation of immune functions; stimulation of growth etc. In this study, we have attempted to find: (i) the critical radiation dose range and the post irradiation period during which the antioxidant defense systems in the lungs, liver and kidneys remain stimulated; and (ii) to evaluate the degree to which these defense mechanisms remain stimulated in these organs after whole body exposure of the animal to low-dose radiation

  9. Homeostatic balance as an indicator of prolonged technogenic exposure in low dose range

    International Nuclear Information System (INIS)

    Karpov, A.B.; Voronova, I.A.; Takhauov, R.M.; Semyonova, Yu.V.; Sherstoboev, E.Yu.; Udut, V.V.

    2008-01-01

    Full text: Indication of changes induced by ionizing radiation starting up a wide range of pathologic reactions in the disease developments still poses a significant problem in radiation medicine. It mainly concerns exposure to low dose-rate ionizing radiation, since its effects are still open to question, and today any researcher acknowledges that radiation induced pathological changes can accumulate at both subclinical and prenosological stages and develop not only in exposed persons, but also in their offspring. The subject of this study was workers of reactor and radiochemical productions of Siberian Group of Chemical Enterprises (SGCE) exposed to external and combined (external and internal) radiation respectively. Two comparative groups were formed: reactor and radiochemical production workers. In the reactor production group of workers the cumulative dose of external γ-radiation was up to 300 mSv, in the radiochemical production group - up to 150 mSv. Age ranged from 40 to 50 years. The two groups were compared between each other. Above all, there were formed 'insider control' groups (workers of the same productions with zero doses) to assess the impact of radiation factor on central homeostatic mechanisms. These groups were created using pair technique in order to level somatic disorders influence on the parameters under study. Numbers of full and biochemical blood examinations, energy metabolism between cells, hormones of homeostasis by the adaptive hormone level - insulin and cortisol, lipid peroxidation and antioxidant protection systems, immune and vegetative systems were all analyzed. Analyses of the systems performed, it was found out that in persons having been exposed to long term occupational radiation there were significant changes indicating lipid peroxidation system activation, antioxidant protection system depression, as well as lowered energy metabolism. The higher external γ-doses the bigger these changes are. Results from the two groups of

  10. Transcriptional responses of the nerve agent-sensitive brain regions amygdala, hippocampus, piriform cortex, septum, and thalamus following exposure to the organophosphonate anticholinesterase sarin

    Directory of Open Access Journals (Sweden)

    Meyerhoff James L

    2011-07-01

    Full Text Available Abstract Background Although the acute toxicity of organophosphorus nerve agents is known to result from acetylcholinesterase inhibition, the molecular mechanisms involved in the development of neuropathology following nerve agent-induced seizure are not well understood. To help determine these pathways, we previously used microarray analysis to identify gene expression changes in the rat piriform cortex, a region of the rat brain sensitive to nerve agent exposure, over a 24-h time period following sarin-induced seizure. We found significant differences in gene expression profiles and identified secondary responses that potentially lead to brain injury and cell death. To advance our understanding of the molecular mechanisms involved in sarin-induced toxicity, we analyzed gene expression changes in four other areas of the rat brain known to be affected by nerve agent-induced seizure (amygdala, hippocampus, septum, and thalamus. Methods We compared the transcriptional response of these four brain regions to sarin-induced seizure with the response previously characterized in the piriform cortex. In this study, rats were challenged with 1.0 × LD50 sarin and subsequently treated with atropine sulfate, 2-pyridine aldoxime methylchloride, and diazepam. The four brain regions were collected at 0.25, 1, 3, 6, and 24 h after seizure onset, and total RNA was processed for microarray analysis. Results Principal component analysis identified brain region and time following seizure onset as major sources of variability within the dataset. Analysis of variance identified genes significantly changed following sarin-induced seizure, and gene ontology analysis identified biological pathways, functions, and networks of genes significantly affected by sarin-induced seizure over the 24-h time course. Many of the molecular functions and pathways identified as being most significant across all of the brain regions were indicative of an inflammatory response. There

  11. Perinatal exposure to low-dose BDE-47, an emergent environmental contaminant, causes hyperactivity in rat offspring.

    Science.gov (United States)

    Suvorov, Alexander; Girard, Sylvie; Lachapelle, Sophie; Abdelouahab, Nadia; Sebire, Guillaume; Takser, Larissa

    2009-01-01

    Polybrominated diphenyl ethers (PBDE) are a group of environmental contaminants increasing in North America. Few data are available on neurobehavioral effects at low-dose exposure. Our goal in the present study was to evaluate whether low-dose BDE-47, which is the most abundant PBDE in human samples, affects the neurobehavioral development of rats. Dams were exposed to vehicle or low-dose BDE-47 (0.002, 0.02 and 0.2 mg/kg body weight) each 5 days from gestational day 15 to postnatal day (PND) 20 by intravenous injections. Spontaneous locomotor activity of pups was assessed using the open field test on PND 15, 20 and 25. Sensorimotor coordination was assessed using a RotaRod on PND 30. Exposure to BDE-47 increased locomotor activity of pups. Developmental landmarks and sensorimotor coordination were not influenced by exposure to BDE-47. BDE-47 content in adipose tissue of exposed rats was similar to that known for human populations. These results indicate neurodevelopmental disruption induced in rats by BDE-47 at levels found in the human population.

  12. The basic approaches to evaluation of effects of the long-therm radiation exposure in a range of 'low' doses

    International Nuclear Information System (INIS)

    Takhauov, R.M.; Karpov, A.B.; Litvyakov, N.V.

    2010-01-01

    The previously performed research allowed forming the main concepts about deterministic effects of radiation impact and defining the main postulates of radiation medicine with respect to average and high levels of exposure. At the same time the research performed to evaluate stochastic effects caused by 'low' doses of ionizing radiation influence failed to find a single-valued answer relating both to dose impact inducing the effect development and to the spectrum of recorded pathologic processes or diseases. In this connection on our opinion the most prospective decision of present problem are studies in follow directions: 1. The evaluation of radiation productions personal and residents of nearby territories mortality and morbidity structure and dynamics. 2. The estimation of risk main diseases development with long-term radiation exposure and analysis of radiation factor role in its pathogenesis. 3. The study of genetic disturbances of persons and their descendants exposed long-term ionizing radiation in 'low' doses. 4. The study of individual radio sensitivity genetic markers. 5. The evaluation of structural and functional homeostasis disturbances inducing the radiation exposure in 'low' doses. The object of study is the Close administrative territorial formation Seversk population and mainly Siberian Group Chemical Enterprises (SGCE) personal - the largest complex productions of atomic industry in the world. The Regional Medico-Dosimetric Register (RMDR), creating since 2001 is the basis for epidemiological studies. The register database contain the information concerning to about 66 000 SGCE workers (it is a whole number of workers in all years of SGCE existence from 1950 to now day). The 35 000 from 66 000 workers are the workers of so-called main productions. About 96% workers exposed external radiation has cumulative dose less 500 mSv. On the base of laboratory of genomic medicine it was created and constantly enriched the bank DNA and biological material

  13. Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E

    2003-07-01

    In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

  14. Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

    International Nuclear Information System (INIS)

    Feinendegen, L.E.

    2003-01-01

    In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

  15. Model of avascular tumor growth and response to low dose exposure

    International Nuclear Information System (INIS)

    Rodriguez Aguirre, J M; Custidiano, E R

    2011-01-01

    A single level cellular automata model is described and used to simulate early tumor growth, and the response of the tumor cells under low dose radiation affects. In this model the cell cycle of the population of normal and cancer cells is followed. The invasion mechanism of the tumor is simulated by a local factor that takes into account the microenvironment hardness to cell development, in a picture similar to the AMTIH model. The response of normal and cancer cells to direct effects of radiation is tested for various models and a model of bystander response is implemented.

  16. Evaluation of experimental animal biological state at exposure to low-dose ionizing radiation

    International Nuclear Information System (INIS)

    Rozanov, V.A.; Rejtarova, T.Je.; Chernyikov, G.B.; Timoshevs'ka, Je.V.; Kozozojeva, O.O.

    1997-01-01

    New approaches to quantitative evaluation of ionizing radiation absorbed dose within the low-dose range (up to 400 mGy) according to the degree of the organism biological response was developed. The purpose of the stage of the work published in Communication 1 is to evaluate the shifts in the animal behaviour and cellular composition of the blood at irradiation by the dose of 100,200 and 400 mGy. Distinct dose dependence of behaviour reactions and hematological indices within the dose range of 100-400 mGy was not noted

  17. Long term/low dose formalin exposure to small-scale recirculation aquaculture systems

    DEFF Research Database (Denmark)

    Pedersen, Lars-Flemming; Pedersen, Per Bovbjerg; Nielsen, Jeppe L.

    2010-01-01

    on a daily basis as compared to untreated systems. In systems intermittently treated with formalin, increased variation and minor reductions of ammonium and nitrite oxidation rates were observed. Nitrifying bacteria were screened by specific gene probes using fluorescence in situ hybridization and quantified...... Nitrobacter sp. was not detected. The relative abundances of AOB and NOB in the untreated system were generally higher compared to the system exposed to formalin. Low dose formalin in recirculated aquaculture systems proved to be a possible treatment strategy, as the effect on nitrification was minimal. Since...

  18. The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

    National Research Council Canada - National Science Library

    Adams, T. K; Capacio, B. R; Smith, J. R; Whalley, C. E; Korte, W. D

    2004-01-01

    The fluoride reactivation process was evaluated for measuring the level of sarin or soman nerve agents reactivated from substrates in plasma and tissue from in vivo exposed guinea pigs (Cava porcellus...

  19. Gene expression analysis after low dose ionising radiation exposure of the developing organism

    International Nuclear Information System (INIS)

    Abderrafi Benotmane, M.

    2007-01-01

    Measuring gene expression using microarrays is relevant to many areas of biology and medicine, such as follow up of developmental stages and diseases onset, and treatment study. Since there can be tens of thousands of distinct probes on an array, each micro array experiment can accomplish the equivalent number of genetic tests in parallel. Arrays have therefore dramatically accelerated many types of investigations. For example, microarrays can be used to identify stress response genes by comparing gene expression in challenged versus normal cells. In the Molecular and Cellular Biology lab (MCB), the micro array experiments are performed within the Genomic Platform, fully equipped to analyse either the behaviour of bacteria during long space flight, the effect of low dose ionising radiation on the developing organism in mice, or the human individual radiation sensitivity. For the low dose effect, two main stages of development are of interest; 1) the gastrula stage at which ionizing radiation can induce several malformations. 2) the organogenesis. During brain development, epidemiological studies of the atomic bomb survivors of Hiroshima/Nagasaki showed increased risk of mental retardation in children of women exposed between weeks 8-15 of pregnancy or at a lower extend between weeks 15 to 25

  20. A study on mice exposure dose for low-dose gamma-irradiation using glass dosimeter

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Sung Jin; Kim, Hyo Jin; Kim, Hyun; Jeong, Dong Hyeok; Son, Tae Gen; Kim, Jung Ki; Yang, Kwang Mo; Kang, Yeong Rok [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Nam, Sang Hee [Dept. of Biomedical Engineering, Inje University, Gimhae (Korea, Republic of)

    2015-12-15

    The low dose radiation is done for a long period, thus researchers have to know the exact dose distribution for the irradiated mouse. This research has been conducted in order to find out methods in transmitting an exact dose to mouse in a mouse irradiation experiment carried out using {sup 137}C{sub s} irradiation equipment installed in the DIRAMS (Dongnam Institution of Radiological and Medical Sciences) research center. We developed a single mouse housing cage and shelf with adjustable geometric factors such as distance and angle from collimator. The measurement of irradiated dose showed a maximal 42% difference of absorbed dose from the desired dose in the conventional irradiation system, whereas only 6% difference of the absorbed dose was measured in the self-developed mouse apartment system. In addition, multi mice housing showed much difference of the absorbed dose in between head and body, compared to single mouse housing in the conventional irradiation system. This research may allow further research about biological effect assessment for the low dose irradiation using the self-developed mouse apartment to provide more exact doses which it tries to transmit, and to have more reliability for the biological analysis results.

  1. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

    Science.gov (United States)

    Goodson, William H; Lowe, Leroy; Carpenter, David O; Gilbertson, Michael; Manaf Ali, Abdul; Lopez de Cerain Salsamendi, Adela; Lasfar, Ahmed; Carnero, Amancio; Azqueta, Amaya; Amedei, Amedeo; Charles, Amelia K; Collins, Andrew R; Ward, Andrew; Salzberg, Anna C; Colacci, Annamaria; Olsen, Ann-Karin; Berg, Arthur; Barclay, Barry J; Zhou, Binhua P; Blanco-Aparicio, Carmen; Baglole, Carolyn J; Dong, Chenfang; Mondello, Chiara; Hsu, Chia-Wen; Naus, Christian C; Yedjou, Clement; Curran, Colleen S; Laird, Dale W; Koch, Daniel C; Carlin, Danielle J; Felsher, Dean W; Roy, Debasish; Brown, Dustin G; Ratovitski, Edward; Ryan, Elizabeth P; Corsini, Emanuela; Rojas, Emilio; Moon, Eun-Yi; Laconi, Ezio; Marongiu, Fabio; Al-Mulla, Fahd; Chiaradonna, Ferdinando; Darroudi, Firouz; Martin, Francis L; Van Schooten, Frederik J; Goldberg, Gary S; Wagemaker, Gerard; Nangami, Gladys N; Calaf, Gloria M; Williams, Graeme; Wolf, Gregory T; Koppen, Gudrun; Brunborg, Gunnar; Lyerly, H Kim; Krishnan, Harini; Ab Hamid, Hasiah; Yasaei, Hemad; Sone, Hideko; Kondoh, Hiroshi; Salem, Hosni K; Hsu, Hsue-Yin; Park, Hyun Ho; Koturbash, Igor; Miousse, Isabelle R; Scovassi, A Ivana; Klaunig, James E; Vondráček, Jan; Raju, Jayadev; Roman, Jesse; Wise, John Pierce; Whitfield, Jonathan R; Woodrick, Jordan; Christopher, Joseph A; Ochieng, Josiah; Martinez-Leal, Juan Fernando; Weisz, Judith; Kravchenko, Julia; Sun, Jun; Prudhomme, Kalan R; Narayanan, Kannan Badri; Cohen-Solal, Karine A; Moorwood, Kim; Gonzalez, Laetitia; Soucek, Laura; Jian, Le; D'Abronzo, Leandro S; Lin, Liang-Tzung; Li, Lin; Gulliver, Linda; McCawley, Lisa J; Memeo, Lorenzo; Vermeulen, Louis; Leyns, Luc; Zhang, Luoping; Valverde, Mahara; Khatami, Mahin; Romano, Maria Fiammetta; Chapellier, Marion; Williams, Marc A; Wade, Mark; Manjili, Masoud H; Lleonart, Matilde E; Xia, Menghang; Gonzalez, Michael J; Karamouzis, Michalis V; Kirsch-Volders, Micheline; Vaccari, Monica; Kuemmerle, Nancy B; Singh, Neetu; Cruickshanks, Nichola; Kleinstreuer, Nicole; van Larebeke, Nik; Ahmed, Nuzhat; Ogunkua, Olugbemiga; Krishnakumar, P K; Vadgama, Pankaj; Marignani, Paola A; Ghosh, Paramita M; Ostrosky-Wegman, Patricia; Thompson, Patricia A; Dent, Paul; Heneberg, Petr; Darbre, Philippa; Sing Leung, Po; Nangia-Makker, Pratima; Cheng, Qiang Shawn; Robey, R Brooks; Al-Temaimi, Rabeah; Roy, Rabindra; Andrade-Vieira, Rafaela; Sinha, Ranjeet K; Mehta, Rekha; Vento, Renza; Di Fiore, Riccardo; Ponce-Cusi, Richard; Dornetshuber-Fleiss, Rita; Nahta, Rita; Castellino, Robert C; Palorini, Roberta; Abd Hamid, Roslida; Langie, Sabine A S; Eltom, Sakina E; Brooks, Samira A; Ryeom, Sandra; Wise, Sandra S; Bay, Sarah N; Harris, Shelley A; Papagerakis, Silvana; Romano, Simona; Pavanello, Sofia; Eriksson, Staffan; Forte, Stefano; Casey, Stephanie C; Luanpitpong, Sudjit; Lee, Tae-Jin; Otsuki, Takemi; Chen, Tao; Massfelder, Thierry; Sanderson, Thomas; Guarnieri, Tiziana; Hultman, Tove; Dormoy, Valérian; Odero-Marah, Valerie; Sabbisetti, Venkata; Maguer-Satta, Veronique; Rathmell, W Kimryn; Engström, Wilhelm; Decker, William K; Bisson, William H; Rojanasakul, Yon; Luqmani, Yunus; Chen, Zhenbang; Hu, Zhiwei

    2015-06-01

    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. © The Author 2015. Published by Oxford University Press.

  2. Effect of continuous exposure to very low dose rates of gamma rays on life span and neoplasia in mice

    International Nuclear Information System (INIS)

    Tanaka, I.B. III; Tanaka, Satoshi; Ichinohe, Kazuaki; Matsumoto, Tsuneya; Otsu, Hiroshi; Oghiso, Yoichi; Sato, Fumiaki; Matsushita, Satoru

    2008-01-01

    Late effects of continuous exposure to ionizing radiation are potential hazards to workers in radiation facilities as well as to the general public. In the recent years, low-dose-rate and low-dose effects have become a serious concern. Using a total of 4,000 mice, we studied the late biological effects of chronic exposure to low-dose-rate radiation on life span and neoplasia. Two thousand male and 2000 female 8-week-old specific pathogen free (SPF) B6C3F1 mice were randomly divided into 4 groups, one non-irradiated (control) and three irradiated. The irradiated groups were exposed to 137 Cs gamma rays at dose-rates of 21, 1.1 and 0.05 mGy day -1 for approximately 400 days with total doses equivalent to 8000, 400 and 20 mGy, respectively. All mice were kept under SPF conditions until natural death and pathological examination was performed to determine the cause of death. Statistical analyses showed that the life spans of mice of both sexes irradiated with 21 mGy day -1 (P -1 (P 86.7% of all deaths. Compared to the non-irradiated controls, incidences of lethal neoplasms were significantly increased for myeloid leukaemia and hemangiosarcoma in males, soft tissue neoplasms and malignant granulosa cell tumors in females exposed to 21 mGy day -1 . The number of multiple primary neoplasms per mouse was significantly increased in mice irradiated at 21 mGy day -1 . Our results suggest that life shortening in mice continuously exposed to low dose-rate gamma rays is due to early death from a variety of neoplasms and not from increased incidence of specific lethal neoplasms. (author)

  3. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

    Science.gov (United States)

    Goodson, William H.; Lowe, Leroy; Carpenter, David O.; Gilbertson, Michael; Manaf Ali, Abdul; Lopez de Cerain Salsamendi, Adela; Lasfar, Ahmed; Carnero, Amancio; Azqueta, Amaya; Amedei, Amedeo; Charles, Amelia K.; Collins, Andrew R.; Ward, Andrew; Salzberg, Anna C.; Colacci, Anna Maria; Olsen, Ann-Karin; Berg, Arthur; Barclay, Barry J.; Zhou, Binhua P.; Blanco-Aparicio, Carmen; Baglole, Carolyn J.; Dong, Chenfang; Mondello, Chiara; Hsu, Chia-Wen; Naus, Christian C.; Yedjou, Clement; Curran, Colleen S.; Laird, Dale W.; Koch, Daniel C.; Carlin, Danielle J.; Felsher, Dean W.; Roy, Debasish; Brown, Dustin G.; Ratovitski, Edward; Ryan, Elizabeth P.; Corsini, Emanuela; Rojas, Emilio; Moon, Eun-Yi; Laconi, Ezio; Marongiu, Fabio; Al-Mulla, Fahd; Chiaradonna, Ferdinando; Darroudi, Firouz; Martin, Francis L.; Van Schooten, Frederik J.; Goldberg, Gary S.; Wagemaker, Gerard; Nangami, Gladys N.; Calaf, Gloria M.; Williams, Graeme P.; Wolf, Gregory T.; Koppen, Gudrun; Brunborg, Gunnar; Lyerly, H. Kim; Krishnan, Harini; Ab Hamid, Hasiah; Yasaei, Hemad; Sone, Hideko; Kondoh, Hiroshi; Salem, Hosni K.; Hsu, Hsue-Yin; Park, Hyun Ho; Koturbash, Igor; Miousse, Isabelle R.; Scovassi, A.Ivana; Klaunig, James E.; Vondráček, Jan; Raju, Jayadev; Roman, Jesse; Wise, John Pierce; Whitfield, Jonathan R.; Woodrick, Jordan; Christopher, Joseph A.; Ochieng, Josiah; Martinez-Leal, Juan Fernando; Weisz, Judith; Kravchenko, Julia; Sun, Jun; Prudhomme, Kalan R.; Narayanan, Kannan Badri; Cohen-Solal, Karine A.; Moorwood, Kim; Gonzalez, Laetitia; Soucek, Laura; Jian, Le; D’Abronzo, Leandro S.; Lin, Liang-Tzung; Li, Lin; Gulliver, Linda; McCawley, Lisa J.; Memeo, Lorenzo; Vermeulen, Louis; Leyns, Luc; Zhang, Luoping; Valverde, Mahara; Khatami, Mahin; Romano, Maria Fiammetta; Chapellier, Marion; Williams, Marc A.; Wade, Mark; Manjili, Masoud H.; Lleonart, Matilde E.; Xia, Menghang; Gonzalez Guzman, Michael J.; Karamouzis, Michalis V.; Kirsch-Volders, Micheline; Vaccari, Monica; Kuemmerle, Nancy B.; Singh, Neetu; Cruickshanks, Nichola; Kleinstreuer, Nicole; van Larebeke, Nik; Ahmed, Nuzhat; Ogunkua, Olugbemiga; Krishnakumar, P.K.; Vadgama, Pankaj; Marignani, Paola A.; Ghosh, Paramita M.; Ostrosky-Wegman, Patricia; Thompson, Patricia A.; Dent, Paul; Heneberg, Petr; Darbre, Philippa; Leung, Po Sing; Nangia-Makker, Pratima; Cheng, Qiang (Shawn); Robey, R.Brooks; Al-Temaimi, Rabeah; Roy, Rabindra; Andrade-Vieira, Rafaela; Sinha, Ranjeet K.; Mehta, Rekha; Vento, Renza; Di Fiore, Riccardo; Ponce-Cusi, Richard; Dornetshuber-Fleiss, Rita; Nahta, Rita; Castellino, Robert C.; Palorini, Roberta; Hamid, Roslida A.; Langie, Sabine A.S.; Eltom, Sakina E.; Brooks, Samira A.; Ryeom, Sandra; Wise, Sandra S.; Bay, Sarah N.; Harris, Shelley A.; Papagerakis, Silvana; Romano, Simona; Pavanello, Sofia; Eriksson, Staffan; Forte, Stefano; Casey, Stephanie C.; Luanpitpong, Sudjit; Lee, Tae-Jin; Otsuki, Takemi; Chen, Tao; Massfelder, Thierry; Sanderson, Thomas; Guarnieri, Tiziana; Hultman, Tove; Dormoy, Valérian; Odero-Marah, Valerie; Sabbisetti, Venkata; Maguer-Satta, Veronique; Rathmell, W.Kimryn; Engström, Wilhelm; Decker, William K.; Bisson, William H.; Rojanasakul, Yon; Luqmani, Yunus; Chen, Zhenbang; Hu, Zhiwei

    2015-01-01

    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. PMID:26106142

  4. Effect of postnatal low-dose exposure to environmental chemicals on the gut microbiome in a rodent model.

    Science.gov (United States)

    Hu, Jianzhong; Raikhel, Vincent; Gopalakrishnan, Kalpana; Fernandez-Hernandez, Heriberto; Lambertini, Luca; Manservisi, Fabiana; Falcioni, Laura; Bua, Luciano; Belpoggi, Fiorella; L Teitelbaum, Susan; Chen, Jia

    2016-06-14

    This proof-of-principle study examines whether postnatal, low-dose exposure to environmental chemicals modifies the composition of gut microbiome. Three chemicals that are widely used in personal care products-diethyl phthalate (DEP), methylparaben (MPB), triclosan (TCS)-and their mixture (MIX) were administered at doses comparable to human exposure to Sprague-Dawley rats from birth through adulthood. Fecal samples were collected at two time points: postnatal day (PND) 62 (adolescence) and PND 181 (adulthood). The gut microbiome was profiled by 16S ribosomal RNA gene sequencing, taxonomically assigned and assessed for diversity. Metagenomic profiling revealed that the low-dose chemical exposure resulted in significant changes in the overall bacterial composition, but in adolescent rats only. Specifically, the individual taxon relative abundance for Bacteroidetes (Prevotella) was increased while the relative abundance of Firmicutes (Bacilli) was reduced in all treated rats compared to controls. Increased abundance was observed for Elusimicrobia in DEP and MPB groups, Betaproteobacteria in MPB and MIX groups, and Deltaproteobacteria in TCS group. Surprisingly, these differences diminished by adulthood (PND 181) despite continuous exposure, suggesting that exposure to the environmental chemicals produced a more profound effect on the gut microbiome in adolescents. We also observed a small but consistent reduction in the bodyweight of exposed rats in adolescence, especially with DEP and MPB treatment (p gut microbiota in adolescent rats; whether these changes lead to downstream health effects requires further investigation.

  5. Low dose prenatal alcohol exposure does not impair spatial learning and memory in two tests in adult and aged rats.

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    Full Text Available Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol ethanol (EtOH or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult or 15 months (Aged of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance.

  6. Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

    International Nuclear Information System (INIS)

    Picano, Eugenio; Vano, Eliseo; Domenici, Luciano; Bottai, Matteo; Thierry-Chef, Isabelle

    2012-01-01

    According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of < 200 mSv, but with head exposure which may (in absence of protection) arrive at a head equivalent dose of 1 to 3 Sv after a professional lifetime (corresponding to a brain equivalent dose around 500 mSv). At this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed

  7. Acute non-stochastic effect of very low dose whole-body exposure, a thymidine equivalent serum factor

    International Nuclear Information System (INIS)

    Feinendegen, L.E.; Muehlensiepen, H.; Porschen, W.; Booz, J.

    1982-01-01

    Whole-body irradiation of mice causes the dose-dependent appearance of a humoral factor in blood serum which inhibits incorporation of 125-IUdR into tissue culture cells. This factor appears even at doses below 0.01 Gy gamma irradiation and thus is probably not related to cell death. Data are presented relating this humoral factor to thymidine. Since at low doses the target size for this effect was calculated to be the entire cell, a cellular effect is postulated linking the site of few primary absorption events, anywhere in the cell, with the cellular membrane, thus causing changes in membrane charge, structure and/or fluidity. This may lead to blocking thymidine acceptance by the cell, and thus would cause a pile-up of thymidine in the reutilization pathway in peripheral blood and would give rise to the observed effect. The effect appears as a temporary disturbance of the physiological equilibrium and should not be related at present to any cellular damage. The acute low-dose effect described has implications for the measurement of low-dose exposure by biological dosimeters and on basic research on membrane function. (author)

  8. Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans.

    Science.gov (United States)

    Chao, Linda L; Zhang, Yu; Buckley, Shannon

    2015-05-01

    We previously found evidence of reduced gray and white matter volume in Gulf War (GW) veterans with predicted low-level exposure to sarin (GB) and cyclosarin (GF). Because loss of white matter tissue integrity has been linked to both gray and white matter atrophy, the current study sought to test the hypothesis that GW veterans with predicted GB/GF exposure have evidence of disrupted white matter microstructural integrity. Measures of fractional anisotropy and directional (i.e., axial and radial) diffusivity were assessed from the 4T diffusion tensor images (DTI) of 59 GW veterans with predicted GB/GF exposure and 59 "matched" unexposed GW veterans (mean age: 48 ± 7 years). The DTI data were analyzed using regions of interest (ROI) analyses that accounted for age, sex, total brain gray and white matter volume, trauma exposure, posttraumatic stress disorder, current major depression, and chronic multisymptom illness status. There were no significant group differences in fractional anisotropy or radial diffusivity. However, there was increased axial diffusivity in GW veterans with predicted GB/GF exposure compared to matched, unexposed veterans throughout the brain, including the temporal stem, corona radiata, superior and inferior (hippocampal) cingulum, inferior and superior fronto-occipital fasciculus, internal and external capsule, and superficial cortical white matter blades. Post hoc analysis revealed significant correlations between higher fractional anisotropy and lower radial diffusivity with better neurobehavioral performance in unexposed GW veterans. In contrast, only increased axial diffusivity in posterior limb of the internal capsule was associated with better psychomotor function in GW veterans with predicted GB/GF exposure. The finding that increased axial diffusivity in a region of the brain that contains descending corticospinal fibers was associated with better psychomotor function and the lack of significant neurobehavioral deficits in veterans

  9. Low-dose exposure to Veratrum album in children causes mild effects--a case series.

    Science.gov (United States)

    Rauber-Lüthy, Christine; Halbsguth, Ulrike; Kupferschmidt, Hugo; König, Naoko; Mégevand, Chloé; Zihlmann, Karin; Ceschi, Alessandro

    2010-03-01

    White or false hellebore (Veratrum album) has a toxicological relevance because of the potential for misidentification of this plant as yellow gentian (Gentiana lutea). We report a retrospective case series of 11 children (8-12 years) with accidental intake of V. album at a youth camp where they had collected herbs for preparing fresh herb tea. Two children (18%) remained asymptomatic. Nine (82%) developed mild gastrointestinal symptoms, six (55%) presented neurological symptoms, and three (27%) showed bradycardia. All children recovered completely within 10 h of ingestion. The plant was identified at the emergency department; however, detection of veratridine and cevadine by means of high-performance liquid chromatography-Mass spectrometry from the blood of the child with the most severe symptoms was negative (limit 0.01 ng/mL). Veratrum species contain more than 200 different alkaloids, which are the principal toxins and are responsible for most clinical symptoms. There are likely multiple mechanisms of toxicity and some of them are only partially understood. The opening of voltage-gated sodium channels is probably one of the most relevant pathophysiological mechanisms. Veratrum album intoxication in children demonstrated the same clinical course as observed in adults. Accidental ingestion of a low dose of the plant had a favorable outcome with supportive care.

  10. Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring

    International Nuclear Information System (INIS)

    Maiellaro, Marília; Correa-Costa, Matheus; Vitoretti, Luana Beatriz; Gimenes Júnior, João Antônio; Câmara, Niels Olsen Saraiva; Tavares-de-Lima, Wothan; Farsky, Sandra Helena Poliselli; Lino-dos-Santos-Franco, Adriana

    2014-01-01

    Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment. - Highlights: • Formaldehyde exposure does not cause lung inflammation in pregnant rats. • Formaldehyde exposure suppresses allergic lung inflammation in the offspring. • Formaldehyde exposure induces oxidative stress in uterine environment

  11. Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring

    Energy Technology Data Exchange (ETDEWEB)

    Maiellaro, Marília [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo (Brazil); Correa-Costa, Matheus [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo (Brazil); Vitoretti, Luana Beatriz; Gimenes Júnior, João Antônio [Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo (Brazil); Câmara, Niels Olsen Saraiva [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo (Brazil); Tavares-de-Lima, Wothan [Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo (Brazil); Farsky, Sandra Helena Poliselli [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo (Brazil); Lino-dos-Santos-Franco, Adriana, E-mail: adrilino@usp.br [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo (Brazil)

    2014-08-01

    Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment. - Highlights: • Formaldehyde exposure does not cause lung inflammation in pregnant rats. • Formaldehyde exposure suppresses allergic lung inflammation in the offspring. • Formaldehyde exposure induces oxidative stress in uterine environment.

  12. The metabolomic approach identifies a biological signature of low-dose chronic exposure to Cesium 137

    International Nuclear Information System (INIS)

    Grison, S.; Grandcolas, L.; Martin, J.C.

    2012-01-01

    Reports have described apparent biological effects of 137 Cs (the most persistent dispersed radionuclide) irradiation in people living in Chernobyl-contaminated territory. The sensitive analytical technology described here should now help assess the relation of this contamination to the observed effects. A rat model chronically exposed to 137 Cs through drinking water was developed to identify biomarkers of radiation-induced metabolic disorders, and the biological impact was evaluated by a metabolomic approach that allowed us to detect several hundred metabolites in biofluids and assess their association with disease states. After collection of plasma and urine from contaminated and non-contaminated rats at the end of the 9-months contamination period, analysis with a liquid chromatography coupled to mass spectrometry (LC-MS) system detected 742 features in urine and 1309 in plasma. Biostatistical discriminant analysis extracted a subset of 26 metabolite signals (2 urinary, 4 plasma non-polar, and 19 plasma polar metabolites) that in combination were able to predict from 68 up to 94% of the contaminated rats, depending on the prediction method used, with a misclassification rate as low as 5.3%. The difference in this metabolic score between the contaminated and non-contaminated rats was highly significant (P=0.019 after ANOVA cross-validation). In conclusion, our proof-of-principle study demonstrated for the first time the usefulness of a metabolomic approach for addressing biological effects of chronic low-dose contamination. We can conclude that a metabolomic signature discriminated 137 Cs-contaminated from control animals in our model. Further validation is nevertheless required together with full annotation of the metabolic indicators. (author)

  13. Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

    Science.gov (United States)

    Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-02-01

    Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

  14. Behavioral effects in mice of postnatal exposure to low-doses of 137-cesium and bisphenol A.

    Science.gov (United States)

    Heredia, Luis; Bellés, Montserrat; LLovet, Maria Isabel; Domingo, Jose L; Linares, Victoria

    2016-01-18

    Bisphenol A (BPA) is the most important plasticizer used in many household products such as polycarbonate plastics or epoxy resins. Public and scientific concerns exist regarding the possibility that the neonatal exposure to BPA may contribute to neurobehavioral disorders. On the other hand, there is little information on the effects of low doses of ionizing radiation during critical phases of postnatal brain development, as well as the combination of radiation and environmental chemicals. In this study, C57BL/6J mice were exposed to low doses of internal radiation ((137)Cs), and/or BPA on postnatal day 10 (PND10). At the age of two months, animals were submitted to several tests to assess anxiety, activity, learning, and memory. Results showed that exposure to (137)Cs, alone or in combination with BPA, increased the anxiety-like of the animals without changing the activity levels. Animals exposed to (137)Cs showed impaired learning, and spatial memory, an impairment that was not observed in the groups co-exposed to BPA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Effects of chronic exposure to low doses of ionizing radiation on the reproductive performance and outcome of an exposed population

    International Nuclear Information System (INIS)

    Mannino, J.A.

    1978-01-01

    This study was designed to test the hypothesis that low doses of ionizing radiation (cumulative dose less than 5.0 rads/yr) effects the reproductive history and/or outcome of a human population. Medically-related personnel who were exposed to low doses of radiation in the course of their employment were compared with medically-related personnel who were not routinely exposed to ionizing radiation. Each population consisted of 3000 persons from the states of Michigan and Ohio. Reproductive performance, history, and outcome of each sample population was compared statistically. Nineteen congenital defects and 47 postnatal defects were recorded for conceptions of the non-exposed population and 50 congenital defects and 83 postnatal defects were recorded for the exposed group. These groups were further broken down as to whether conception took place before, during, or after exposure and the results statistically analyzed. It was found that the exposure population had greater than expected numbers of postnatal defects and less than expected numbers of normal conceptions

  16. Behavioral effects in mice of postnatal exposure to low-doses of 137-cesium and bisphenol A

    International Nuclear Information System (INIS)

    Heredia, Luis; Bellés, Montserrat; LLovet, Maria Isabel; Domingo, Jose L.; Linares, Victoria

    2016-01-01

    Bisphenol A (BPA) is the most important plasticizer used in many household products such as polycarbonate plastics or epoxy resins. Public and scientific concerns exist regarding the possibility that the neonatal exposure to BPA may contribute to neurobehavioral disorders. On the other hand, there is little information on the effects of low doses of ionizing radiation during critical phases of postnatal brain development, as well as the combination of radiation and environmental chemicals. In this study, C57BL/6J mice were exposed to low doses of internal radiation ( 137 Cs), and/or BPA on postnatal day 10 (PND10). At the age of two months, animals were submitted to several tests to assess anxiety, activity, learning, and memory. Results showed that exposure to 137 Cs, alone or in combination with BPA, increased the anxiety-like of the animals without changing the activity levels. Animals exposed to 137 Cs showed impaired learning, and spatial memory, an impairment that was not observed in the groups co-exposed to BPA.

  17. Perinatal exposure to low-dose imidacloprid causes ADHD-like symptoms: Evidences from an invertebrate model study.

    Science.gov (United States)

    Kim, Seoyoung; Lee, Hee-Seok; Park, Yooheon

    2017-12-01

    The fundamental diagnoses of attention deficit hyperactivity disorder (ADHD) and autism consists of inattention, hyperactivity, and impulsivity, which lead to abnormal social interactions and repetitive and restricted behavior. Several food contaminants are suspected of being a possible contributing factor to the present-day increase in diseases, such as obesity and ADHD, and pesticides are also considered as a contributor to the increased prevalence of ADHD. Imidacloprid is a neonicotinoid insecticide with lower toxicity to mammals. Based on recent reports on neurobehavioral studies using an invertebrate model system, we have assessed ADHD-related impairments to test the effects of low-dose exposure to imidacloprid in Drosophila melanogaster through behavior assays, such as abnormal social interaction, repetitive behaviors, and significant deficiency in locomotion in an open field arena, a decision-making process. Drosophila stocks were treated with imidacloprid at the level of 200 pM. Social interaction among the flies was disturbed by imidacloprid. Travelled distance and velocity was also increased by the treatment. The difference in velocity between the treatment group and the control group was significant, revealing that imidacloprid-exposed flies moved faster and longer than control flies. This study illustrated the behavioral deficiency in Drosophila due to the low-dose imidacloprid exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. FREQUENCY OF CHROMOSOMAL ABERRATIONS AND MICRONUCLEI IN HORSE LYMPHOCYTES FOLLOWING IN VITRO EXPOSURE TO LOW DOSE IONISING RADIATION

    Directory of Open Access Journals (Sweden)

    Dunja Rukavina

    2012-07-01

    Full Text Available Ionising radiation is known to cause chromosomal instability, which is observed as increased frequency of chromosomal aberration and micronuclei. These are listed as reliable criteria in biological dosimetry. Numerous experiments conducted on both animal and plant models demonstrated that increase in radiation dosage is followed by increased mutation frequency, and that mutations occur even at the lowest exposure. We used horse blood in vitro irradiated by low doses of ionizing radiation. Cultivation of peripheral blood lymphocytes and micronucleus test were used as biomarkers of genetic damage. The observed aberrations were recorded and classified in accordance with the International System of Cytogenetic Nomenclature. Micronuclei were identified on the basis of criteria proposed by Fenech et al. (8. Analysis of chromosomal aberration showed increased frequency of aberrations in blood cultures exposed to 0,1 Gy and 0,2 Gy compared to the controls. Microscopic analysis of chromosomal damage in in vitro micronucleus test revealed that the applied radiation dose induced micronuclei while no binucleated cells with micronuclei were found in lymphocytes that were not irradiated. In this paper we analysed the influence of low dose ionising radiation on frequency of chromosomal aberration and micronuclei in horse lymphocytes following in vitro exposure to X-rays (0,1 Gy and 0,2 Gy. Key words: chromosomal aberrations, micronuclei, ionising radiation, horse lymphocytes

  19. Low-dose prenatal alcohol exposure modulates weight gain and eliminates fractalkine expression in e14.5 mouse embryos

    Directory of Open Access Journals (Sweden)

    Jordyn Karliner

    2017-07-01

    Full Text Available Fetal Alcohol Spectrum Disorder (FASD is caused by maternal alcohol consumption during pregnancy and often leads to long-lasting developmental symptoms, including increased microglial migration and increased release of the chemokine, fractalkine, both of which play a role in embryonic brain development. However, the effects of low-dose alcohol exposure on microglia and fractalkine embryonically are not well documented. This study addresses this gap by using the voluntary drinking paradigm, Drinking in the Dark (DiD, to expose mice to acute doses of alcohol from embryonic day 7.5 (E7.5 to E14.5. Maternal mice and embryo analyses revealed increased embryo weights and a trend of increased gestational weight gain in alcohol-exposed mice compared to water-exposed mice. After quantifying soluble fractalkine concentrations through Western Blots, results indicated decreased fractalkine in alcohol-exposed mice compared to water-exposed. Overall, our data suggest that exposure to low doses of alcohol inhibits fractalkine release, which may affect microglial function.

  20. Tritium β-radiation induction of chromosomal damage: a calibration curve for low dose, low dose rate exposures of human cells to tritiated water

    International Nuclear Information System (INIS)

    Morrison, D.P.; Gale, K.L.; Lucas, J.N.

    1997-01-01

    Radiation exposures from tritium contribute to the occupational radiation exposures associated with CANDU reactors. Tritiated water is of particular interest since it is readily taken up by human cells and its elimination from the body, and, consequently, the radiation exposure of the cells, is spread over a period of days. Occupational exposures to tritiated water result in what are effectively chronic β-radiation exposures. The doses and dose rates ordinarily used in the definition of cellular responses to radiation in vitro, for use in biological dosimetry (the assessment of radiation exposures based on the observed levels of changes in the cells of exposed individuals), are usually much higher than for most occupational exposures and involve radiations other than tritium β-rays. As a result, their use in assessing the effects from tritiated water exposures may not be appropriate. We describe here an in vitro calibration curve for chronic tritium β-radiation induction of reciprocal chromosomal translocations in humn peripheral blood lymphocytes (PBLs) for use in biodosimetry. (author)

  1. Issues with using radiological exposures as a company performance measure in a low dose environment

    International Nuclear Information System (INIS)

    Wilkins, Richard I.

    2008-01-01

    Full text: Collective and maximum individual doses are two measures commonly used as an indicator for measuring Company performance. There is often an expectation for year on year improvements by optimisation of exposures through improved working methods and modernisation of facilities. Eventually a level of exposure can be reached that is no longer easy to measure which makes meaningful trend analysis difficult. The paper discusses the issues that arose at AWE where the majority of exposures are close the limit of detection for the TLD system used. It details the investigation that was carried out when recorded doses where observed to unexpectedly increase significantly. The paper shows the significant effect of a small change in the background radiation levels that are subtracted for each individual dose measurement. Also discussed is the effect of using TLD dosimeter readers that have undergone recent maintenance and are therefore assessing slightly increased exposures. Compounding the apparent increase in gamma dose a slight change in the manufacturing process for the plastic neutron film in the neutron dosimeters also gave an increased neutron exposure measurement which is detailed. The paper concludes with describing the changes that have been made to better ensure reproducibility of the exposure measurements so that any improvements in Company performance can be shown. It also questions the use of Collective Dose as a performance measure which is commonly misused across the industry. (author)

  2. TU-C-18A-01: Models of Risk From Low-Dose Radiation Exposures: What Does the Evidence Say?

    International Nuclear Information System (INIS)

    Bushberg, J; Boreham, D; Ulsh, B

    2014-01-01

    what dose level are risk vs. benefit discussions with patients appropriate, 3) at what dose level should we tell a pregnant woman that the baby’s health risk from a prenatal radiation exposure is “significant”, 4) is informed consent needed for patients undergoing medical imaging, and 5) at what dose level is evacuation appropriate after a radiological accident. Examples of the tremendous impact that choosing different risks models can have on the answers to these types of questions will be given.A moderated panel discussion will allow audience members to pose questions to the faculty members, each of whom is an established expert in his respective discipline. Learning Objectives: Understand the fundamental principles, strengths and limitations of radiation epidemiology and radiation biology for determining the risk from exposures to low doses of ionizing radiation Become familiar with common models of risk used to describe the dose-response relationship at low dose levels Learn to identify strengths and weaknesses in studies designed to measure the effect of low doses of ionizing radiation Understand the implications of different risk models on public policy and health care decisions

  3. TU-C-18A-01: Models of Risk From Low-Dose Radiation Exposures: What Does the Evidence Say?

    Energy Technology Data Exchange (ETDEWEB)

    Bushberg, J [UC Davis Medical Center, Sacramento, CA (United States); Boreham, D [McMaster University, Ontario, CA (Canada); Ulsh, B

    2014-06-15

    what dose level are risk vs. benefit discussions with patients appropriate, 3) at what dose level should we tell a pregnant woman that the baby’s health risk from a prenatal radiation exposure is “significant”, 4) is informed consent needed for patients undergoing medical imaging, and 5) at what dose level is evacuation appropriate after a radiological accident. Examples of the tremendous impact that choosing different risks models can have on the answers to these types of questions will be given.A moderated panel discussion will allow audience members to pose questions to the faculty members, each of whom is an established expert in his respective discipline. Learning Objectives: Understand the fundamental principles, strengths and limitations of radiation epidemiology and radiation biology for determining the risk from exposures to low doses of ionizing radiation Become familiar with common models of risk used to describe the dose-response relationship at low dose levels Learn to identify strengths and weaknesses in studies designed to measure the effect of low doses of ionizing radiation Understand the implications of different risk models on public policy and health care decisions.

  4. Lung cancer incidence after exposure of rats to low doses of radon: influence of dose rate

    Energy Technology Data Exchange (ETDEWEB)

    Morlier, J.P.; Morin, M.; Monchaux, G.; Fritsch, P.; Lafuma, J.; Masse, R. [CEA Centre d`Etudes Nucleaires de Fontenay-aux-Roses, 92 (France). Dept. de Protection Technique; Pineau, J.F. [ALGADE, Bessines (France); Chameaud, J. [Compagnie Generale des Matieres Nucleaires (COGEMA), 87 - Razes (France)

    1994-12-31

    To study the effect on lung cancer incidence of a long exposure to low levels of radon, 500 male 3-months-old Sprague-Dawley rats, were exposed to a cumulative dose of 25 WLM of radon and its daughters, 6 hours a day, 5 days a week, during 18 months. Exposure conditions were controlled in order to maintain a defined PAEC: 42 x 10{sup 6} J.m{sup -3} (2 WL), in the range of domestic and environmental exposures. Animals were kept until they died or given euthanasia when moribund. Mean survival times were similar in both irradiated and control groups: 828 days (SD = 169) and 830 days (SD = 137), as well as lung cancer incidence, 0.60% at 25 WLM and 0.63% for controls. The incidence of lung lesions was compared statistically with controls and those previously obtained at cumulative exposures of 25 and 50 WLM delivered over a 4-6 month period, inducing a significant increase of lung cancer, 2.2% and 3.8% respectively. Such a comparison showed a decreased lung cancer incidence related to a decrease in the dose rate for low levels of radon exposure. (author).

  5. Lung cancer incidence after exposure of rats to low doses of radon: influence of dose rate

    International Nuclear Information System (INIS)

    Morlier, J.P.; Morin, M.; Monchaux, G.; Fritsch, P.; Lafuma, J.; Masse, R.; Chameaud, J.

    1994-01-01

    To study the effect on lung cancer incidence of a long exposure to low levels of radon, 500 male 3-months-old Sprague-Dawley rats, were exposed to a cumulative dose of 25 WLM of radon and its daughters, 6 hours a day, 5 days a week, during 18 months. Exposure conditions were controlled in order to maintain a defined PAEC: 42 x 10 6 J.m -3 (2 WL), in the range of domestic and environmental exposures. Animals were kept until they died or given euthanasia when moribund. Mean survival times were similar in both irradiated and control groups: 828 days (SD = 169) and 830 days (SD = 137), as well as lung cancer incidence, 0.60% at 25 WLM and 0.63% for controls. The incidence of lung lesions was compared statistically with controls and those previously obtained at cumulative exposures of 25 and 50 WLM delivered over a 4-6 month period, inducing a significant increase of lung cancer, 2.2% and 3.8% respectively. Such a comparison showed a decreased lung cancer incidence related to a decrease in the dose rate for low levels of radon exposure. (author)

  6. Complex mixtures: Relevance of combined exposure to substances at low dose levels

    NARCIS (Netherlands)

    Leeman, W.R.; Krul, L.; Houben, G.F.

    2013-01-01

    Upon analysis of chemically complex food matrices a forest of peaks is likely to be found. Identification of these peaks and concurrent determination of the toxicological relevance upon exposure is very time consuming, expensive and often requires animal studies. Recently, a safety assessment

  7. Combined exposure to low doses of pesticides causes decreased birth weights in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Christiansen, Sofie; Petersen, Marta Axelstad

    2017-01-01

    Decreased birth weight is a common effect of many pesticides in reproductive toxicity studies, but there are no empirical data on how pesticides act in combination on this endpoint. We hypothesized that a mixture of six pesticides (cyromazine, MCPB, pirimicarb, quinoclamine, thiram, and ziram) wo...... to avoid potentially serious impact of mixed exposure on prenatal development and pregnancy in humans....

  8. Low-dose effect of developmental bisphenol A exposure on sperm count and behaviour in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Christiansen, Sofie; Boberg, Julie

    2016-01-01

    /day. In the offspring, growth, sexual maturation, weights and histopathology of reproductive organs, oestrus cyclicity and sperm counts were assessed. Neurobehavioural development was investigated using a behavioural testing battery including tests for motor activity, sweet preference, anxiety and spatial learning....... Decreased sperm count was found at the lowest bisphenol A dose, that is 25 μg/kg/day, but not at the higher doses. Reproductive organ weight and histology were not affected and no behavioural effects were seen in male offspring. In the female offspring, exposure to 25 μg/kg bw/day bisphenol A dose resulted...... not significantly affected. In conclusion, the present study using a robust experimental study design, has shown that developmental exposure to 25 μg/kg bw/day bisphenol A can cause adverse effects on fertility (decreased sperm count), neurodevelopment (masculinization of spatial learning in females) and lead...

  9. Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells

    DEFF Research Database (Denmark)

    Dreyer-Andersen, Nanna; Almeida, Ana Sofia; Jensen, Pia

    2018-01-01

    cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting...... in both protection and generation of reactive oxygen species. The present study investigated the effect of CO produced by a novel CO-releasing molecule on dopaminergic differentiation of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4 significantly increased the relative content...... of β-tubulin III-immunoreactive immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons, as assessed 6 days after differentiation. Also the number of microtubule associated protein 2-positive mature neurons had increased significantly. Moreover, the content of apoptotic cells...

  10. High dose and low dose radiation exposure in the induction of breast cancer

    International Nuclear Information System (INIS)

    Fernandez-Vicioso, E.; Ruiz-Cruces, R.; Pastor Vega, Jose M.

    2001-01-01

    In today's modern practice of Radiation Oncology it is becoming increasingly common to follow many patients with breast cancer. There is a proven association between prior radiation and the development of breast cancer, although in many instances the available sources of data are confusing. Characteristic features of radiation induced breast cancer are the importance of age at first exposure to radiation and the long latency period. The risk of breast cancer is highest in women exposed in the first decade of life and lessens progressively with increased age at exposure. The latency period is typically 10 years or more; a time in which other age dependent factors may influence the expression of the malignant phenotype. Genetic factors may also (in theory) increase a particular patient's susceptibility. (author)

  11. Breast cancer incidence following low-dose rate environmental exposure: Techa River Cohort, 1956–2004

    Science.gov (United States)

    Ostroumova, E; Preston, D L; Ron, E; Krestinina, L; Davis, F G; Kossenko, M; Akleyev, A

    2008-01-01

    In the 1950s, the Mayak nuclear weapons facility in Russia discharged liquid radioactive wastes into the Techa River causing exposure of riverside residents to protracted low-to-moderate doses of radiation. Almost 10 000 women received estimated doses to the stomach of up to 0.47 Gray (Gy) (mean dose=0.04 Gy) from external γ-exposure and 137Cs incorporation. We have been following this population for cancer incidence and mortality and as in the general Russian population, we found a significant temporal trend of breast cancer incidence. A significant linear radiation dose–response relationship was observed (P=0.01) with an estimated excess relative risk per Gray (ERR/Gy) of 5.00 (95% confidence interval (CI), 0.80, 12.76). We estimated that approximately 12% of the 109 observed cases could be attributed to radiation. PMID:19002173

  12. Induction of potent local cellular immunity with low dose X4 SHIVSF33A vaginal exposure

    International Nuclear Information System (INIS)

    Tasca, Silvana; Tsai, Lily; Trunova, Nataliya; Gettie, Agegnehu; Saifuddin, Mohammed; Bohm, Rudolf; Chakrabarti, Lisa; Cheng-Mayer, Cecilia

    2007-01-01

    Intravaginal inoculation of rhesus macaques with varying doses of the CXCR4 (X4)-tropic SHIV SF33A isolate revealed a threshold inoculum for establishment of systemic virus infection and a dose dependency in overall viral burden and CD4+ T cell depletion. While exposure to inoculum size of 1000 or greater 50% tissue infectious dose (TCID 50 ) resulted in high viremia and precipitous CD4+ T cell loss, occult infection was observed in seven of eight macaques exposed to 500 TCID 50 of the same virus. The latter was characterized by intermittent detection of low level virus with no evidence of seroconversion or CD4+ T cell decline, but with signs of an ongoing antiviral T cell immune response. Upon vaginal re-challenge with the same limiting dose 11-12 weeks after the first, classic pathogenic X4 SHIV SF33A infection was established in four of the seven previously exposed seronegative macaques, implying enhanced susceptibility to systemic infection with prior exposure. Pre-existing peripheral SIV gag-specific CD4+ T cells were more readily demonstrable in macaques that became systemically infected following re-exposure than those that were not. In contrast, early presence of circulating polyfunctional cytokine secreting CD8+ T cells or strong virus-specific proliferative responses in draining lymph nodes and in the gut associated lymphoid tissue (GALT) following the first exposure was associated with protection from systemic re-infection. These studies identify the gut and lymphoid tissues proximal to the genital tract as sites of robust CD8 T lymphocyte responses that contribute to containment of virus spread following vaginal transmission

  13. Obesity in the United States—dysbiosis from exposure to low-dose antibiotics?

    Directory of Open Access Journals (Sweden)

    Lee W Riley

    2013-12-01

    Full Text Available The rapid increase in obesity prevalence in the United States in the last 20 years is unprecedented and not well explained. Here, we explore a hypothesis that the obesity epidemic may be driven by population-wide chronic exposures to low-residue antibiotics that have increasingly entered the American food chain over the same time period. We propose this hypothesis based on two recent bodies of published reports—1 those that provide evidence for the spread of antibiotics into the American food chain, and 2 those that examine the relationship between the gut microbiota and body physiology. The livestock use of antimicrobial agents has sharply increased in the US over the same 20-year period of the obesity epidemic, especially with the expansion of intensified livestock production, such as the concentrated animal feeding operations (CAFOs. Observational and experimental studies support the idea that changes in the intestinal microbiota exert a profound effect on body physiology. We propose that chronic exposures to low-residue antimicrobial drugs in food could disrupt the equilibrium state of intestinal microbiota and cause dysbiosis that can contribute to changes in body physiology. The obesity epidemic in the United States may be partly driven by the mass exposure of Americans to food containing low-residue antimicrobial agents. While this hypothesis cannot discount the impact of diet and other factors associated with obesity, we believe studies are warranted to consider this possible driver of the epidemic.

  14. Susceptibility of linear and nonlinear otoacoustic emission components to low-dose styrene exposure.

    Science.gov (United States)

    Tognola, G; Chiaramello, E; Sisto, R; Moleti, A

    2015-03-01

    To investigate potential susceptibility of active cochlear mechanisms to low-level styrene exposure by comparing TEOAEs in workers and controls. Two advanced analysis techniques were applied to detect sub-clinical changes in linear and nonlinear cochlear mechanisms of OAE generation: the wavelet transform to decompose TEOAEs into time-frequency components and extract signal-to-noise ratio and latency of each component, and the bispectrum to detect and extract nonlinear TEOAE contributions as quadratic frequency couplings (QFCs). Two cohorts of workers were examined: subjects exposed exclusively to styrene (N = 9), and subjects exposed to styrene and noise (N = 6). The control group was perfectly matched by age and sex to the exposed group. Exposed subjects showed significantly lowered SNR in TEOAE components at mid-to-high frequencies (above 1.6 kHz) and a shift of QFC distribution towards lower frequencies than controls. No systematic differences were observed in latency. Low-level styrene exposure may have induced a modification of cochlear functionality as concerns linear and nonlinear OAE generation mechanisms. The lack of change in latency seems to suggest that the OAE components, where generation region and latency are tightly coupled, may not have been affected by styrene and noise exposure levels considered here.

  15. Antagonistic effects of gestational dietary exposure to low-dose vinclozolin and genistein on rat fetal germ cell development.

    Science.gov (United States)

    Lehraiki, Abdelali; Messiaen, Sébastien; Berges, Raymond; Canivenc-Lavier, Marie-Chantal; Auger, Jacques; Habert, René; Levacher, Christine

    2011-05-01

    Continuous, low-dose exposure to a phytoestrogen (1 mg/kg/day genistein) and/or to an antiandrogenic food contaminant (1 mg/kg/day vinclozolin) has been recently reported to affect male reproductive tract and fertility [1] in adults. We investigated whether alterations of the testis are already present at the end of in utero exposure using the same rat model and doses following exposure from conception to delivery. After vinclozolin exposure, we observed in the neonate a slight but significant alteration of steroidogenesis and gametogenesis with a reduction of testosterone secretion and of the number of gonocytes. In contrast, genistein exposure had no effect. While the vinclozolin-genistein mixture acts in a synergistic manner to induce the most significant alterations in the adult, interestingly, genistein antagonized the deleterious effect of vinclozolin on germ cells in the neonate. This difference emphasizes the importance of studying the effects of endocrine disruptors during various developmental stages to understand their effects. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Toxic Effects of a Whole-Body Inhalation Sarin (GR) Vapor Exposure in the Gottingen Minipig

    National Research Council Canada - National Science Library

    Hulet, S. W; Jakubowski, E. M; Dabisch, P. A; Foster, J. S; Miller, D. B; Benton, B. J; Muse, W. T; Way, R. A; Edwards, J. L; McGuire, J.M

    2004-01-01

    .... In order to assess the toxic hazards of such exposures and define chemical defense materiel requirements, it is essential to fill gaps in toxicological databases that define the physiological progression...

  17. Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells

    DEFF Research Database (Denmark)

    Dreyer-Andersen, Nanna; Almeida, Ana Sofia; Jensen, Pia

    2018-01-01

    Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem...... cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting...... in Parkinson's disease....

  18. Epidemiologic study on respiratory cancer among miners with low dose radiation exposures

    International Nuclear Information System (INIS)

    Comba, P.

    1993-01-01

    The aim of the project is the study of specific mortality causes among Italian miners, with special reference to respiratory malignancies. The contrast between observed and expected mortality rates for lung cancer of miners exposed to different levels of radiation provide figures for estimating the number of extra cases of lung cancer per working level month and person years of exposure. The study included 1357 subjects, 60 of whom were lost to follow-up. The total number of deceased subjects was 527; for 30 of them it was not possible to ascertain the cause of death. (R.P.) 2 refs., 3 tabs

  19. The Assessment of DNA Damage in Poultry Spermatozoa after Exposure to Low Doses of Ionising Radiation

    International Nuclear Information System (INIS)

    Kasuba, V.; Milic, M.; Pejakovic Hlede, J.; Gottstein, Z.; Karadjole, M.; Miljanic, S.

    2013-01-01

    The existence of dose-related induction of DNA strand breaks in spermatozoa following in vitro exposure to ionising radiation represents sperm DNA integrity as an important parameter in the evaluation of semen functionality. Maintaining of normal sperm becomes even more important when it is known that DNA in semen samples is already fragmentated in certain amount in human and turkey semen and that it lacks DNA repair mechanisms making DNA damage irreversible. The aim of this paper was to provide an insight in the amount of DNA damage detected in chicken spermatozoa (5 cocks, 45 weeks old) of heavy line after radiation with doses of 0.3, 0.5, 1 and 2 Gy gamma radiation and to address the question of the potential ecological consequences of the damage that was measured with comet assay. Scored parameters included tail intensity, tail length and tail moment. Results showed sensitivity of comet assay technique that detected significant DNA damage even after exposure to 0.3 Gy, but also showed no dose-related responses after 0.5, 1 and 2 Gy. Distribution of damaged cells was widely spread for the higher doses, showing the influence of possible adaptive response, but for further conclusions, larger studies are needed to answer that question.(author)

  20. Prenatal and lactational exposure to low-doses of bisphenol A alters adult mice behavior.

    Science.gov (United States)

    Nakamura, Keiko; Itoh, Kyoko; Dai, Hongmei; Han, Longzhe; Wang, Xiaohang; Kato, Shingo; Sugimoto, Tohru; Fushiki, Shinji

    2012-01-01

    Bisphenol A (BPA) is an endocrine-disrupting chemical, widely used in dentistry and various industries. We previously reported that BPA affected murine neocortical development by accelerating neuronal differentiation/migration, resulting in abnormal neocortical architecture as well as aberrant thalamocortical connections in the brains of adult mice. The aim of this study was to investigate whether prenatal and lactational BPA exposure affected behavior in adult mice. Pregnant mice were injected subcutaneously with 20μg/kg of BPA daily from embryonic day 0 (E0) until postnatal day 21 (P21). Control animals received a vehicle alone. Behavioral tests (n=15-20) were conducted at postnatal 3weeks (P3W) and P10-15W. After an open-field test, an elevated plus maze and Morris water maze tests were performed. The total distance in the elevated plus maze test at P3W and in the open-field test at P10W was significantly decreased in the BPA-exposed group, compared with the control group. Significant sex differences were observed in the time spent in the central area in the open-field test at P3W and in the total distance in the elevated plus maze test at P11W. These results indicated that prenatal and lactational BPA exposure disturbed the murine behavior in the postnatal development period and the adult mice. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  1. Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

    Science.gov (United States)

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

    2009-01-01

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

  2. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    International Nuclear Information System (INIS)

    Lowe, Xiu R.; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-01-01

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p -53 ) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease

  3. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-06-06

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.

  4. Effect of anxiolytic aphobazole on hemopoietic system under exposure to low doses of ionizing radiation and emotional stress

    International Nuclear Information System (INIS)

    Moroz, B.B.; Deshevoj, Yu.B.; Seredenin, S.B.; Lyrshchikova, A.V.; Lebedev, V.G.

    2001-01-01

    Effect of aphobazole in investigated on the course of adaptation reactions and state of compensatory capabilities of hemopoietic system of rats-males under long-term emotional stress developed following the low-dose gamma-radiation. Gamma-quanta from 137 Cs source at 0.9 Gy dose (1.3 Gy/min dose rate) were used for single and uniform irradiation of animals. Two days later rats were exposed to long-term emotional stress. Aphobazole at the dose of 10.0 mg/kg was incorporated into rats once a day. It is shown that aphobazole permits to stop the violations in adaptation reactions and compensatory capabilities of hemopoietic system under conditions of emotional stress development in the early period following the exposure to gamma radiation at 0.9 Gy dose [ru

  5. [Complex pathogenetic treatment schemes of vascular dyscirculatory disorders in the remote period after exposure to low dose radiation].

    Science.gov (United States)

    Holodova, N B; Zhavoronkova, L A; Ryzhov, B N

    2013-01-01

    Complex studies including modern methods of investigation of structures and functions of nervous system: electroencephalograsphy (EEG), coherent analysis, neuropsychological study and methods of neuroimaging were performed in 517 participants in liquidation of consequences of the accident (LCA) at the Chernobyl NPP in 1986-1987. Dyscirculatory metabolic encephalopathy was revealed to be the main pathology with the etiological mechanism based on dyscirculatorhypoxic and metabolic disorders. Complexity of the revealed symptoms testified to an early organism aging in remote periods after exposure to low dose radiation. Pathogenetic schemes were developed for treatment of dyscirculatory encephalopathy in liquidators, which include drugs improving blood supply, antiaggregants, antioxidants and metabolites of the brains in various combinations. Taking into consideration that early appearance of vascular dyscirculatory disorders observed in liquidators is the sign of early aging of the organism, geroprotectors were added to treatment schemes.

  6. Targeted computerised tomography scanning of the ankle syndesmosis with low dose radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kotwal, Rahul [Princess of Wales Hospital, Bridgend (United Kingdom); Rath, Narendra [Royal Gwent Hospital, Newport (United Kingdom); Paringe, Vishal; Hemmadi, Sandeep; Thomas, Rhys; Lyons, Kath [University Hospital of Wales, Cardiff (United Kingdom)

    2016-03-15

    To devise a new protocol for targeted CT scanning of the distal tibiofibular syndesmosis with minimal radiation exposure to patients. We also aimed to correlate the reduction of the syndesmosis as seen on CT scans with the functional outcome of patients. Prospective study. Forty adults undergoing surgical stabilisation of an acute distal tibiofibular syndesmosis injury were recruited. A targeted five-cut computerised tomography scan protocol was developed. The radiation exposure to the patient with this protocol was only 0.002 mSv. Scans were performed 12 weeks after surgery. The contralateral ankle of every patient was used as a control to determine the accuracy of the reduction of the syndesmosis for that individual patient. American Orthopaedic Foot and Ankle Society (AOFAS) scores were obtained at a minimum of 1 year after surgery. After considering the exclusions, 36 patients formed the study group. A wide variation was observed in the anatomy of the normal syndesmosis. If we considered a difference of more than 2 mm between the normal and injured syndesmosis relationship as significant, 15 (41.6 %) of our patients had a significant difference between the injured and normal sides. AOFAS scores were available for 13 of these patients and were good to excellent in 11(84.6 %). Our study describes a reliable new CT scanning technique for the distal tibiofibular syndesmosis using only five cuts and a low-radiation-dose protocol. Clinical correlation of the findings on the scan with functional outcomes suggests that routine post-operative CT of the syndesmosis is probably not justified. (orig.)

  7. Targeted computerised tomography scanning of the ankle syndesmosis with low dose radiation exposure

    International Nuclear Information System (INIS)

    Kotwal, Rahul; Rath, Narendra; Paringe, Vishal; Hemmadi, Sandeep; Thomas, Rhys; Lyons, Kath

    2016-01-01

    To devise a new protocol for targeted CT scanning of the distal tibiofibular syndesmosis with minimal radiation exposure to patients. We also aimed to correlate the reduction of the syndesmosis as seen on CT scans with the functional outcome of patients. Prospective study. Forty adults undergoing surgical stabilisation of an acute distal tibiofibular syndesmosis injury were recruited. A targeted five-cut computerised tomography scan protocol was developed. The radiation exposure to the patient with this protocol was only 0.002 mSv. Scans were performed 12 weeks after surgery. The contralateral ankle of every patient was used as a control to determine the accuracy of the reduction of the syndesmosis for that individual patient. American Orthopaedic Foot and Ankle Society (AOFAS) scores were obtained at a minimum of 1 year after surgery. After considering the exclusions, 36 patients formed the study group. A wide variation was observed in the anatomy of the normal syndesmosis. If we considered a difference of more than 2 mm between the normal and injured syndesmosis relationship as significant, 15 (41.6 %) of our patients had a significant difference between the injured and normal sides. AOFAS scores were available for 13 of these patients and were good to excellent in 11(84.6 %). Our study describes a reliable new CT scanning technique for the distal tibiofibular syndesmosis using only five cuts and a low-radiation-dose protocol. Clinical correlation of the findings on the scan with functional outcomes suggests that routine post-operative CT of the syndesmosis is probably not justified. (orig.)

  8. Low-dose mutation-response relationships in Tradescantia; principles and comparison to mutagenesis following low-dose gaseous chemical mutagen exposure

    International Nuclear Information System (INIS)

    Nauman, C.H.; Sparrow, A.H.; Underbrink, A.G.; Schairer, L.A.

    1976-01-01

    Inflorescences of several clones of Tradescantia heterozygous for flower color have been treated with ionizing radiation and with the gaseous form of several known or suspected chemical mutagens. Pink somatic mutations were subsequently scored in the stamen hair cells of mature flowers and dose-/exposure-response curves constructed. Results indicate clearly that there is no evidence for a threshold for mutation response following x or neutron irradiation. Results so far obtained for gaseous chemical mutagens are less clear, but also suggest that there is no threshold for mutation response

  9. Low-dose effect of developmental bisphenol A exposure on sperm count and behaviour in rats.

    Science.gov (United States)

    Hass, U; Christiansen, S; Boberg, J; Rasmussen, M G; Mandrup, K; Axelstad, M

    2016-07-01

    Bisphenol A is widely used in food contact materials and other products and is detected in human urine and blood. Bisphenol A may affect reproductive and neurological development; however, opinion of the European Food Safety Authority (EFSA) on bisphenol A (EFSA J, 13, 2015 and 3978) concluded that none of the available studies were robust enough to provide a point of departure for setting a tolerable daily intake for bisphenol A. In the present study, pregnant Wistar rats (n = 17-21) were gavaged from gestation day 7 to pup day 22 with bisphenol A doses of 0, 25 μg, 250 μg, 5 mg or 50 mg/kg bw/day. In the offspring, growth, sexual maturation, weights and histopathology of reproductive organs, oestrus cyclicity and sperm counts were assessed. Neurobehavioural development was investigated using a behavioural testing battery including tests for motor activity, sweet preference, anxiety and spatial learning. Decreased sperm count was found at the lowest bisphenol A dose, that is 25 μg/kg/day, but not at the higher doses. Reproductive organ weight and histology were not affected and no behavioural effects were seen in male offspring. In the female offspring, exposure to 25 μg/kg bw/day bisphenol A dose resulted in increased body weight late in life and altered spatial learning in a Morris water maze, indicating masculinization of the brain. Decreased intake of sweetened water was seen in females from the highest bisphenol A dose group, also a possible sign of masculinization. The other investigated endpoints were not significantly affected. In conclusion, the present study using a robust experimental study design, has shown that developmental exposure to 25 μg/kg bw/day bisphenol A can cause adverse effects on fertility (decreased sperm count), neurodevelopment (masculinization of spatial learning in females) and lead to increased female body weight late in life. These results suggest that the new EFSA temporary tolerable daily intake of 4 μg/kg bw

  10. Subacute effects of low dose lead nitrate and mercury chloride exposure on kidney of rats.

    Science.gov (United States)

    Apaydın, Fatma Gökçe; Baş, Hatice; Kalender, Suna; Kalender, Yusuf

    2016-01-01

    Lead nitrate and mercury chloride are the most common heavy metal pollutants. In the present study, the effects of lead and mercury induced nephrotoxicity were studied in Wistar rats. Lead nitrate (LN, 45 mg/kg b.w/day) and mercury chloride (MC, 0.02 mg/kg b.w/day) and their combination were administered orally for 28 days. Four groups of rats were used in the study: control, LN, MC and LN plus MC groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in kidney tissues were investigated in all treatment groups. LN and MC caused severe histopathological changes. It was shown that LN, MC and also co-treatment with LN and MC exposure induced significant increase in serum urea, uric acid and creatinine levels. There were also statistically significant changes in antioxidant enzyme activities (SOD, CAT, GPx and GST) and lipid peroxidation (MDA) in all groups except control group. In this study, we showed that MC caused more harmful effects than LN in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Physiological Responses in Chinese Rare Minnow Larvae Following Exposure to Low-Dose Tributyltin.

    Science.gov (United States)

    Li, Ping; Li, Zhi-Hua

    2015-11-01

    In the present study, the antioxidant response and acetylcholinesterase (AChE) activity were measured in Chinese rare minnow larvae (Gobiocypris rarus) after exposure to tributyltin (TBT) (0, 100, 400 and 800 ngL(-1)) for 7 days, as well as the expression of a series of genes, including cr, aptase and prl genes involved in the ion-regulatory process and igfbp3 and gh related to growth rate. Results shows that oxidative stress was generated in fish exposed to TBT, as evidenced by elevated malondialdehyde levels and the inhibition of antioxidant parameters. The activity of acetylcholinesterase (AChE) was also inhibited in fish under higher TBT stress. Moreover, genes involved in ion regulation and growth were affected, based on the regulated transcription of the cr, atpase, gh, prl and igfbp3 genes in the treated groups. The observed effects of TBT upon antioxidant responses and altered expression of genes provides insight into the use of these molecular biomarkers in evaluating mechanisms of TBT toxicity in fish.

  12. EUV patterning using CAR or MOX photoresist at low dose exposure for sub 36nm pitch

    Science.gov (United States)

    Thibaut, Sophie; Raley, Angélique; Lazarrino, Frederic; Mao, Ming; De Simone, Danilo; Piumi, Daniele; Barla, Kathy; Ko, Akiteru; Metz, Andrew; Kumar, Kaushik; Biolsi, Peter

    2018-04-01

    The semiconductor industry has been pushing the limits of scalability by combining 193nm immersion lithography with multi-patterning techniques for several years. Those integrations have been declined in a wide variety of options to lower their cost but retain their inherent variability and process complexity. EUV lithography offers a much desired path that allows for direct print of line and space at 36nm pitch and below and effectively addresses issues like cycle time, intra-level overlay and mask count costs associated with multi-patterning. However it also brings its own sets of challenges. One of the major barrier to high volume manufacturing implementation has been hitting the 250W power exposure required for adequate throughput [1]. Enabling patterning using a lower dose resist could help move us closer to the HVM throughput targets assuming required performance for roughness and pattern transfer can be met. As plasma etching is known to reduce line edge roughness on 193nm lithography printed features [2], we investigate in this paper the level of roughness that can be achieved on EUV photoresist exposed at a lower dose through etch process optimization into a typical back end of line film stack. We will study 16nm lines printed at 32 and 34nm pitch. MOX and CAR photoresist performance will be compared. We will review step by step etch chemistry development to reach adequate selectivity and roughness reduction to successfully pattern the target layer.

  13. The estimate reproductive health status of populations exposured in low doses in result of Chernobyl disaster

    International Nuclear Information System (INIS)

    Ljaginskaja, A.M.; Izhewskij, P.W.; Golovko, O.V.

    1996-01-01

    In general the results achieved show that in the population living on the territories contaminated with radionuclides the most distinct negative dynamic of reproductive health than in the control areas is observed dourly the post-accidental period. The highest intensively of the negative dynamic and for certain the lower (than in the control) absolute indices of the reproductive health are revealed in the population living on the territory with 137 Cs contamination from 5 Ci/km 2 to 15 Ci/km 2 Under the equal conditions of 137 Cs contamination of soil the most distinct decrease of indices of the reproductive health was revealed in the areas with the most original level of the reproductive health that witness about the important role of the original level of the reproductive health in forming the effects of the exposure of the population. In the structure of the chosen indices of the reproductive health the loading place according to the intensively of the negative dynamic takes the indices characterising UPO and the status of the newborns, that is the indices reflecting the somatic stochastic effects of radiation influence. (author)

  14. Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis

    International Nuclear Information System (INIS)

    Jansen-van der Weide, Marijke C.; Greuter, Marcel J.W.; Pijnappel, Ruud M.; Jansen, Liesbeth; Oosterwijk, Jan C.; Bock, Geertruida H. de

    2010-01-01

    Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women. A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). Of 127 articles found, 7 were selected for the meta-analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of ≥5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk. Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques. (orig.)

  15. Subchronic exposure to low-doses of the nerve agent VX: Physiological, behavioral, histopathological and neurochemical studies

    International Nuclear Information System (INIS)

    Bloch-Shilderman, Eugenia; Rabinovitz, Ishai; Egoz, Inbal; Raveh, Lily; Allon, Nahum; Grauer, Ettie; Gilat, Eran; Weissman, Ben Avi

    2008-01-01

    The highly toxic organophosphorous compound VX [O-ethyl-S-(isoporopylaminoethyl) methyl phosphonothiolate] undergoes an incomplete decontamination by conventional chemicals and thus evaporates from urban surfaces, e.g., pavement, long after the initial insult. As a consequence to these characteristics of VX, even the expected low levels should be examined for their potential to induce functional impairments including those associated with neuronal changes. In the present study, we developed an animal model for subchronic, low-dose VX exposure and evaluated its effects in rats. Animals were exposed to VX (2.25 μg/kg/day, 0.05 LD 50 ) for three months via implanted mini osmotic pumps. The rapidly attained continuous and marked whole-blood cholinesterase inhibition (∼ 60%), fully recovered 96 h post pump removal. Under these conditions, body weight, blood count and chemistry, water maze acquisition task, sensitivity to the muscarinic agonist oxotremorine, peripheral benzodiazepine receptors density and brain morphology as demonstrated by routine histopathology, remained unchanged. However, animals treated with VX showed abnormal initial response in an Open Field test and a reduction (∼ 30%) in the expression of the exocytotic synaptobrevin/vesicle associate membrane protein (VAMP) in hippocampal neurons. These changes could not be detected one month following termination of exposure. Our findings indicate that following a subchronic, low-level exposure to the chemical warfare agent VX some important processes might be considerably impaired. Further research should be addressed towards better understanding of its potential health ramifications and in search of optimal countermeasures

  16. Effect of Exposure to Pill Contraceptive Low-dose Levels of Homocysteine and Nitric Oxide in Healthy Women

    Directory of Open Access Journals (Sweden)

    A Dehghani

    2016-07-01

    Full Text Available Introduction: Cardiovascular disease is one of the public health priorities. Consumption of oral contraceptives increase the risk of cardiovascular disease and it still remains a concern. This study aimed to investigate the effect of exposure on pill contraceptive low-dose  levels on homocysteine and nitric oxide. methods: In this cohort ( retrospective+ prospective study, 100 women with normal menstrual cycle aged betwen 20-35 years old refered to health care centers of Yazd, Iran in 2015.  This study was conducted through face to face interviews by the researcher who asked for demographic and anthropometric characteristics. Anthropometic indices  was measured and the levels of homosysteine and nitric oxide was determined. The data were analyzed using t-test, chi- square test and ANOVA by SPSS 21. Results: The mean and standard deviation of homocysteine levels in the exposed group acompared to non-exposed group were (3/848±2/357 μmol/L and (3/284±1/616 μmol/L as well as the mean and standard deviation of nitric oxide in the exposed group were (p-value=0/41 and (181/360±90/44μM and in the non-exposed group were (162/654±90/913 μM and (p-value=0/29 , respectively.According to these results, there was not found any statistical significant  difference among these results. Conclusion: Taking low dose oral contraceptives in healthy women did not change any differences in homocysteine and nitric oxide levels as a modifiable risk factors for cardiovascular disease.

  17. Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility.

    Science.gov (United States)

    Eustache, Florence; Mondon, Françoise; Canivenc-Lavier, Marie Chantal; Lesaffre, Corinne; Fulla, Yvonne; Berges, Raymond; Cravedi, Jean Pierre; Vaiman, Daniel; Auger, Jacques

    2009-08-01

    The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood. We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility. Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays. The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the "neuroactive ligand-receptor interactions" family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production. Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose-albeit not environmental-of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility.

  18. Neuropsychological effects of chronic low-dose exposure to polychlorinated biphenyls (PCBs: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Klett Martin

    2005-10-01

    Full Text Available Abstract Background Exposure to indoor air of private or public buildings contaminated with polychlorinated biphenyls (PCBs has raised health concerns in long-term users. This exploratory neuropsychological group study investigated the potential adverse effects of chronic low-dose exposure to specific air-borne low chlorinated PCBs on well-being and behavioral measures in adult humans. Methods Thirty employees exposed to indoor air contaminated with PCBs from elastic sealants in a school building were compared to 30 non-exposed controls matched for education and age, controlling for gender (age range 37–61 years. PCB exposure was verified by external exposure data and biological monitoring (PCB 28, 101, 138, 153, 180. Subjective complaints, learning and memory, executive function, and visual-spatial function was assessed by standardized neuropsychological testing. Since exposure status depended on the use of contaminated rooms, an objectively exposed subgroup (N = 16; PCB 28 = 0.20 μg/l; weighted exposure duration 17.9 ± 7 years was identified and compared with 16 paired controls. Results Blood analyses indicated a moderate exposure effect size (d relative to expected background exposure for total PCB (4.45 ± 2.44 μg/l; d = 0.4. A significant exposure effect was found for the low chlorinated PCBs 28 (0.28 ± 0.25 μg/l; d = 1.5 and 101 (0.07 ± 0.09 μg/l; d = 0.7. Although no neuropsychological effects exceeded the adjusted significance level, estimation statistics showed elevated effect sizes for several variables. The objectively exposed subgroup showed a trend towards increased subjective attentional and emotional complaints (tiredness and slowing of practical activities, emotional state as well as attenuated attentional performance (response shifting and alertness in a cued reaction task. Conclusion Chronic inhalation of low chlorinated PCBs that involved elevated blood levels was associated with a subtle attenuation of emotional well

  19. Renal and hepatic effects following neonatal exposure to low doses of Bisphenol-A and 137Cs.

    Science.gov (United States)

    Esplugas, Roser; LLovet, Maria Isabel; Bellés, Montserrat; Serra, Noemí; Vallvé, Joan Carles; Domingo, José Luis; Linares, Victoria

    2018-04-01

    137-Cesium ( 137 Cs) is one of the most important distributed radionuclides after a nuclear accident. Humans are usually co-exposed to various environmental toxicants, being Bisphenol-A (BPA) one of them. Exposure to IR and BPA in early life is of major concern, due to the higher vulnerability of developing organs. We evaluate the renal and hepatic effects of low doses of ionizing radiation (IR) and BPA. Sixty male mice (C57BL/6J) were randomly assigned to six experimental groups (n=10) and received a single subcutaneous dose of 0.9% saline solution, 137 Cs and/or BPA on postnatal day 10: control, BPA (25 μg/kgbw), Cs4000 (4000 Bq 137 Cs/kgbw), Cs8000 (8000 Bq 137 Cs/kgbw), BPA/Cs4000 and BPA/Cs8000. At the age of two months, urines (24h) and blood samples were collected from animals of each group to determine biochemical parameters. Finally, kidneys and liver were removed to quantify DNA damage (8-OHdG), as well as to determine CYP1A2 mRNA expression. Data suggest that both BPA and 137 Cs induced renal and liver damage evidenced by oxidative stress. However, when there is a co-exposure, it seems that there are compensatory mechanisms that may reverse the damage induced by each toxic itself. Notwithstanding, more studies are necessary to better understand the synergistic mechanisms behind. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Sex-specific effects of low-dose gestational estradiol-17β exposure on bone development in porcine offspring

    International Nuclear Information System (INIS)

    Flöter, Veronika L.; Galateanu, Gabriela; Fürst, Rainer W.; Seidlová-Wuttke, Dana; Wuttke, Wolfgang; Möstl, Erich; Hildebrandt, Thomas B.

    2016-01-01

    Highlights: • Sex-specific effects and non-monotonic dose responses were demonstrated after low-dose in utero E2 treatment in offspring. • Alterations in bone parameters were found in prepubertal male but not female offspring. • In postpubertal female offspring, cortical and total cross-sectional area were higher at the femoral midpoint. • In utero E2 treatment did neither significantly affect hormone concentrations nor puberty onset in offspring. • The results substantiate the high sensitivity of developing organisms to exogenous estrogens. - Abstract: Estrogens are important for the bone development and health. Exposure to endocrine disrupting chemicals during the early development has been shown to affect the bone phenotype later in life. Several studies have been performed in rodents, while in larger animals that are important to bridge the gap to humans there is a paucity of data. To this end, the pig as large animal model was used in the present study to assess the influence of gestational estradiol-17β (E2) exposure on the bone development of the prepubertal and adult offspring. Two low doses (0.05 and 10 μg E2/kg body weight) referring to the ‘acceptable daily intake’ (ADI) and the ‘no observed effect level’ (NOEL) as stated for humans, and a high-dose (1000 μg E2/kg body weight), respectively, were fed to the sows every day from insemination until delivery. In the male prepubertal offspring, the ADI dose group had a lower strength strain index (p = 0.002) at the proximal tibia compared to controls, which was determined by peripheral quantitative computed tomography. Prepubertal females were not significantly affected. However, there was a higher cortical cross-sectional area (CSA) (p = 0.03) and total CSA (p = 0.02) at the femur midpoint in the adult female offspring of the NOEL dose group as measured by computed tomography. These effects were independent from plasma hormone concentrations (leptin, IGF1, estrogens), which remained

  1. Maternal low-dose estradiol-17β exposure during pregnancy impairs postnatal progeny weight development and body composition

    International Nuclear Information System (INIS)

    Werner Fürst, Rainer; Pistek, Veronika Leopoldine; Kliem, Heike; Skurk, Thomas; Hauner, Hans; Meyer, Heinrich Herman Dietrich; Ulbrich, Susanne Ernestine

    2012-01-01

    Endocrine disrupting chemicals with estrogenic activity play an important role as obesogens. However, studies investigating the most potent natural estrogen, estradiol-17β (E2), at low dose are lacking. We examined endocrine and physiological parameters in gilts receiving distinct concentrations of E2 during pregnancy. We then investigated whether adverse effects prevail in progeny due to a potential endocrine disruption. E2 was orally applied to gilts during the entire period of pregnancy. The concentrations represented a daily consumption at the recommended ADI level (0.05 μg/kg body weight/day), at the NOEL (10 μg/kg body weight/day) and at a high dosage (1000 μg/kg body weight/day). Plasma hormone concentrations were determined using enzyme immuno assays. Offspring body fat was assessed by dual-energy X-ray absorptiometry scanning. In treated gilts receiving 1000 μg E2/kg body weight/day we found significantly elevated plasma E2 levels during pregnancy, paralleled by an increased weight gain. While offspring showed similar weight at birth, piglets exhibited a significant reduction in weight at weaning even though their mothers had only received 0.05 μg E2/kg body weight/day. At 8 weeks of age, specifically males showed a significant increase in overall body fat percentage. In conclusion, prenatal exposure to low doses of E2 affected pig offspring development in terms of body weight and composition. In line with findings from other obesogens, our data suggest a programming effect during pregnancy for E2 causative for the depicted phenotypes. Therefore, E2 exposure may imply a possible contribution to childhood obesity. -- Highlights: ► We investigate the potential role of estradiol-17β (E2) as an obesogen. ► We orally apply E2 at the ADI, NOEL and a high dose to gilts during pregnancy. ► Offspring weight is similar at birth but reduced at weaning even after ADI treatment. ► Male offspring only exhibit an increase in overall body fat percentage

  2. Maternal low-dose estradiol-17β exposure during pregnancy impairs postnatal progeny weight development and body composition

    Energy Technology Data Exchange (ETDEWEB)

    Werner Fürst, Rainer [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); ZIEL PhD Graduate school ‘Epigenetics, Imprinting and Nutrition’, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Pistek, Veronika Leopoldine; Kliem, Heike [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Skurk, Thomas; Hauner, Hans [ZIEL Dep. Nutritional Medicine, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Klinikum rechts der Isar, Technische Universität München, 81675 München (Germany); Meyer, Heinrich Herman Dietrich [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Ulbrich, Susanne Ernestine, E-mail: ulbrich@wzw.tum.de [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany)

    2012-09-15

    Endocrine disrupting chemicals with estrogenic activity play an important role as obesogens. However, studies investigating the most potent natural estrogen, estradiol-17β (E2), at low dose are lacking. We examined endocrine and physiological parameters in gilts receiving distinct concentrations of E2 during pregnancy. We then investigated whether adverse effects prevail in progeny due to a potential endocrine disruption. E2 was orally applied to gilts during the entire period of pregnancy. The concentrations represented a daily consumption at the recommended ADI level (0.05 μg/kg body weight/day), at the NOEL (10 μg/kg body weight/day) and at a high dosage (1000 μg/kg body weight/day). Plasma hormone concentrations were determined using enzyme immuno assays. Offspring body fat was assessed by dual-energy X-ray absorptiometry scanning. In treated gilts receiving 1000 μg E2/kg body weight/day we found significantly elevated plasma E2 levels during pregnancy, paralleled by an increased weight gain. While offspring showed similar weight at birth, piglets exhibited a significant reduction in weight at weaning even though their mothers had only received 0.05 μg E2/kg body weight/day. At 8 weeks of age, specifically males showed a significant increase in overall body fat percentage. In conclusion, prenatal exposure to low doses of E2 affected pig offspring development in terms of body weight and composition. In line with findings from other obesogens, our data suggest a programming effect during pregnancy for E2 causative for the depicted phenotypes. Therefore, E2 exposure may imply a possible contribution to childhood obesity. -- Highlights: ► We investigate the potential role of estradiol-17β (E2) as an obesogen. ► We orally apply E2 at the ADI, NOEL and a high dose to gilts during pregnancy. ► Offspring weight is similar at birth but reduced at weaning even after ADI treatment. ► Male offspring only exhibit an increase in overall body fat percentage

  3. Thyroid hormone levels and hepatic enzyme activity in lactating dams after gestational exposure to low dose PBDE 47

    Energy Technology Data Exchange (ETDEWEB)

    Kuriyama, S.N.; Grande, S.W.; Akkoc, Z.; Souza, C.A.M. de; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin; Fidalgo-Neto, A.A. [Oswaldo Cruz Foundation, Rio de Janeiro (Brazil). Lab. of Environmental Toxicology

    2004-09-15

    Polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants, are found extensively in the environment (shown by several studies on sentinel animal species), as well as in humans. In rodents, technical commercial PBDE mixtures and individual congeners have shown to interfere with thyroid hormone homeostasis, produce a mix-type induction of hepatic microsomal enzymes, disrupt spontaneous behaviour, impair learning and memory and alter the cholinergic transmitter system. In rat and mice, some technical PBDE commercial mixtures such as DE-71 and Bromkal 70 and the congener PBDE 47 have shown to decrease circulating thyroid hormone levels. PBDEs are also able to induce both hepatic phase I and phase II detoxification enzymes, demonstrated by several investigations in laboratory animals. For example, induction of ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-Odespenthylase (PROD) and uridinediphospho-glucuronosyltransferase (UDPGT) has been shown in rodents and cell lines after exposure to technical mixtures or individual congeners. However, these studies deal with doses much higher than that found in human tissues, highlighting the importance of assessing the adverse effects of doses close to human exposure levels. PBDE 47 is the most predominant congener found in environmental and human samples (including human milk) and, therefore, hazard identification is extremely important for human risk assessment. We administered a single dose to gravid dams on gestation day 6 of either 140 {mu}g/kg BW or 700 {mu}g/kg BW of the congener, 2,2'4,4'-tetrabromo diphenyl ether (PBDE 47). These doses are pertinent to human exposure levels because a study by She et al. found a mean level of 33.3 {mu}g PBDE 47 /kg fat in human breast adipose tissue with a range from 7.01 to 196 {mu}g PBDE 47 /kg fat. In this study, thyroid hormone levels and hepatic enzyme activity were evaluated in lactating dams after in utero administration of low dose PBDE 47.

  4. Study on cancer induced by long-term exposure to low dose rate radiation and its treatment

    International Nuclear Information System (INIS)

    Takahashi, Shinji

    1980-01-01

    For the purpose of discovering measures to prevent carcinogenesis by exposure to low dose radiation, radiological and clinical studies were carried out on patients with previous thorotrast injection. X-ray findings of these patients were classified into 8 types; the amount of injected thorotrast was not proportional to the size of the liver or spleen. CT could visualize sites of lymph nodes where thorotrast was remained and intrahepatic distribution of thorotrast. CT was also useful for detecting hepatic carcinoma. The amounts of thorotrast in each organ were calculated from the measurement by the whole body counter, and interstitial thorotrast was identified by fluorescent x-ray analysis. Numerical chromosome aberrations were found in all 9 patients with thorotrast; structural chromosome aberrations were found in 3 of the 9 patients. The appearance rates of small nuclei and H-J bodies in the bone marrow were higher in these patients than in controls. When patients with thorotrast had liver failure, their conditions deteriorated rapidly. Amino acid transfusion by Fisher's description was effective for hepatic encephalopathy. Out of 170 necropsied cases with thorotrast, 112 had malignant tumors of the liver with statistically significance compared to the control population. (Tsunoda, M.)

  5. Study on cancer induced by long-term exposure to low dose rate radiation and its treatment

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, S. (Hamamatsu Univ. School of Medicine, Shizuoka (Japan))

    1980-06-01

    For the purpose of discovering measures to prevent carcinogenesis by exposure to low dose radiation, radiological and clinical studies were carried out on patients with previous thorotrast injection. X-ray findings of these patients were classified into 8 types; the amount of injected thorotrast was not proportional to the size of the liver or spleen. CT could visualize sites of lymph nodes where thorotrast was remained and intrahepatic distribution of thorotrast. CT was also useful for detecting hepatic carcinoma. The amounts of thorotrast in each organ were calculated from the measurement by the whole body counter, and interstitial thorotrast was identified by fluorescent x-ray analysis. Numerical chromosome aberrations were found in all 9 patients with thorotrast; structural chromosome aberrations were found in 3 of the 9 patients. The appearance rates of small nuclei and H-J bodies in the bone marrow were higher in these patients than in controls. When patients with thorotrast had liver failure, their conditions deteriorated rapidly. Amino acid transfusion by Fisher's description was effective for hepatic encephalopathy. Out of 170 necropsied cases with thorotrast, 112 had malignant tumors of the liver with statistically significance compared to the control population.

  6. Effect of prenatal exposure to low dose beta radiation from tritiated water on postnatal growth and neurobehavior of rats

    International Nuclear Information System (INIS)

    Gao Weimin; Zhou Xiangyan

    1998-01-01

    Objective: Effects of prenatal exposure to HTO (tritiated water) on postnatal growth and neurobehavior of rats were studied by determination of multiple parameters. Methods: Pregnant adult Wistar rats were randomly assigned to 4 groups, of which 3 groups were irradiated with beta-rays from tritiated water (HTO) by one single intraperitoneal injection on the 13th day of gestation. Offspring of these rats received cumulative doses of 0.000, 0.044, 0.088 and 0.264 Gy utero, respectively, and were observed for the appearance of three physiologic markers (eye opening, pinna detachment, incisor eruption), the age of acquisition of two reflexes (surface righting, negative geotaxis) and sensuous function (auditory startle), movement and coordination functions and activity (forelimb hanging, continuous corridor activity), and learning and memory (electric avoidance reflex in Y-maze, conditional reflex). Results: Results for most parameters in the 0.044 and 0.088 Gy groups were different significantly from those in the controls and for most parameters a dose-dependent effect was found. Conclusion: Offspring of rats having received prenatal low dose irradiation from HTO showed delayed growth and abnormal neurobehavior

  7. Effects of Low Doses of Ionizing Radiation Exposures on Stress-Responsive Gene Expression in Human Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Mykyta Sokolov

    2014-01-01

    Full Text Available There is a great deal of uncertainty on how low (≤0.1 Gy doses of ionizing radiation (IR affect human cells, partly due to a lack of suitable experimental model systems for such studies. The uncertainties arising from low-dose IR human data undermine practical societal needs to predict health risks emerging from diagnostic medical tests’ radiation, natural background radiation, and environmental radiological accidents. To eliminate a variability associated with remarkable differences in radioresponses of hundreds of differentiated cell types, we established a novel, human embryonic stem cell (hESC-based model to examine the radiobiological effects in human cells. Our aim is to comprehensively elucidate the gene expression changes in a panel of various hESC lines following low IR doses of 0.01; 0.05; 0.1 Gy; and, as a reference, relatively high dose of 1 Gy of IR. Here, we examined the dynamics of transcriptional changes of well-established IR-responsive set of genes, including CDKN1A, GADD45A, etc. at 2 and 16 h post-IR, representing “early” and “late” radioresponses of hESCs. Our findings suggest the temporal- and hESC line-dependence of stress gene radioresponses with no statistically significant evidence for a linear dose-response relationship within the lowest doses of IR exposures.

  8. Low-dose-rate radiation exposure leads to testicular damage with decreases in DNMT1 and HDAC1 in the murine testis

    International Nuclear Information System (INIS)

    Gong, Eun Ji; Son, Tae Gen; Yang, Kwangmo; Heo, Kyu; Kim, Joong Sun; Shin, In Sik

    2014-01-01

    This study examined the effects of continuous low-dose-rate radiation exposure (3.49 mGy/h) of gamma rays on mice testicles. C57BL/6 mice were divided into sham and radiation groups (n = 8 each), and were exposed to either sham irradiation or 2 Gy for 21 days, 0.2 Gy for 2 days, or 0.02 Gy for 6 h of low-dose-rate irradiation. Testicular weight, seminiferous tubular diameter, and seminiferous epithelial depth were significantly decreased in the mice irradiated with 2 Gy at 1 and 9 days after exposure. Moreover, the low-dose-rate radiation exposure induced an increase in malondialdehyde levels, and a decrease in superoxide dismutase activity in the testis of mice irradiated with 2 Gy at 1 and 9 days after exposure. The sperm count and motility in the epididymis also decreased in mice irradiated with 2 Gy at 1 and 9 days after exposure, whereas there was no significant effect on the proportion of abnormal sperm. The expressions of DNA methlytransferases-1 and histone deacetylases 1 in testes irradiated with 2 Gy were significantly decreased compared with the sham group. In conclusion, the damage exerted on the testes and epididymis largely depended on the total dose of low-dose-rate radiation. (author)

  9. Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice

    Energy Technology Data Exchange (ETDEWEB)

    Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; Begriche, Karima [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Trak-Smayra, Viviane [Pathology Department, Saint-Joseph University, Beirut (Lebanon); Martinais, Sophie [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Porceddu, Mathieu [Mitologics SAS, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris (France); Robin, Marie-Anne [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Fromenty, Bernard, E-mail: bernard.fromenty@inserm.fr [INSERM, U991, Université de Rennes 1, 35000 Rennes (France)

    2014-04-01

    Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 10{sup 6} ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 10{sup 6} ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 10{sup 2}–10{sup 3} ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants. - Highlights: • The contamination of drinking water with drugs may have harmful effects on health. • Some drugs can be more hepatotoxic in the context of obesity and fatty liver. • Effects of chronic exposure of trace drugs were studied in lean and obese mouse liver. Drugs and obesity present additive effects on circadian gene expression and toxicity. • Trace

  10. Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland.

    Directory of Open Access Journals (Sweden)

    Perinaaz R Wadia

    Full Text Available Exposure of rodent fetuses to low doses of the endocrine disruptor bisphenol A (BPA causes subtle morphological changes in the prenatal mammary gland and results in pre-cancerous and cancerous lesions during adulthood. To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a associated with changes in mRNA expression reflecting estrogenic actions and/or b dependent on the estrogen receptor α (ERα, we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2 on fetal mammary tissues of wild type and ERα knock-out mice. Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E 8 were harvested at E19. Transcriptomal analyses on the ductal epithelium and periductal stroma revealed altered expression of genes involved in the focal adhesion and adipogenesis pathways in the BPA-exposed stroma while genes regulating the apoptosis pathway changed their expression in the BPA-exposed epithelium. These changes in gene expression correlated with previously reported histological changes in matrix organization, adipogenesis, and lumen formation resulting in enhanced maturation of the fat-pad and delayed lumen formation in the epithelium of BPA-exposed fetal mammary glands. Overall similarities in the transcriptomal effects of BPA and EE2 were more pronounced in the epithelium, than in the stroma. In addition, the effects of BPA and EE2 on the expression of various genes involved in mammary stromal-epithelial interactions were suppressed in the absence of ERα. These observations support a model whereby BPA and EE2 act directly on the stroma, which expresses ERα, ERβ and GPR30 in fetal mammary glands, and that the stroma, in turn, affects gene expression in the epithelium, where ERα and ERβ are below the level of detection at this stage of development.

  11. Disruption of thyroid hormone functions by low dose exposure of tributyltin: an in vitro and in vivo approach.

    Science.gov (United States)

    Sharan, Shruti; Nikhil, Kumar; Roy, Partha

    2014-09-15

    Triorganotins, such as tributyltin chloride (TBTCl), are environmental contaminants that are commonly found in the antifouling paints used in ships and other vessels. The importance of TBTCl as an endocrine-disrupting chemical (EDC) in different animal models is well known; however, its adverse effects on the thyroid gland are less understood. Hence, in the present study, we aimed to evaluate the thyroid-disrupting effects of this chemical using both in vitro and in vivo approaches. We used HepG2 hepatocarcinoma cells for the in vitro studies, as they are a thyroid hormone receptor (TR)-positive and thyroid responsive cell line. For the in vivo studies, Swiss albino male mice were exposed to three doses of TBTCl (0.5, 5 and 50μg/kg/day) for 45days. TBTCl showed a hypo-thyroidal effect in vivo. Low-dose treatment of TBTCl exposure markedly decreased the serum thyroid hormone levels via the down-regulation of the thyroid peroxidase (TPO) and thyroglobulin (Tg) genes by 40% and 25%, respectively, while augmenting the thyroid stimulating hormone (TSH) levels. Thyroid-stimulating hormone receptor (TSHR) expression was up-regulated in the thyroid glands of treated mice by 6.6-fold relative to vehicle-treated mice (p<0.05). In the transient transactivation assays, TBTCl suppressed T3 mediated transcriptional activity in a dose-dependent manner. In addition, TBTCl was found to decrease the expression of TR. The present study thus indicates that low concentrations of TBTCl suppress TR transcription by disrupting the physiological concentrations of T3/T4, followed by the recruitment of NCoR to TR, providing a novel insight into the thyroid hormone-disrupting effects of this chemical. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Alzheimer ’s Disease: Possible Mechanisms Behind Neurohormesis Induced by Exposure to Low Doses of Ionizing Radiation

    Science.gov (United States)

    Bevelacqua, J.J.; Mortazavi, S.M.J.

    2018-01-01

    In 2016, scientists reported that human exposure to low doses of ionizing radiation (CT scans of the brain) might relieve symptoms of both Alzheimer’s disease (AD) and Parkinson disease (PD). The findings were unbelievable for those who were not familiar with neurohormesis. X-ray stimulation of the patient’s adaptive protection systems against neurodegenerative diseases was the mechanism proposed by those authors. Now, some more recent studies performed in the field of neurobiological research confirm that low levels of stress can produce protective responses against the pathogenic processes. This paper outlines possible protective consequences of LDR in preventing the pathogenesis of AD through mechanisms such as restoring the myelin sheath and preventing neurodegeneration caused by oxidative stress. Focal demyelination is frequently reported in the proximity of beta-amyloid plaques within neocortex. Extracellular accumulation of amyloid is among well-characterized pathological changes in AD. It should be noted that LDR has been shown to contribute to the regeneration and functional recovery after transverse peripheral nerve injury (through inducing increased production of VEGF and GAP-43), which advances both the axonal regeneration and myelination. Another mechanism which is possibly involved is preventing neurodegeneration caused by oxidative stress. While high doses can induce reactive oxygen species (ROS) formation, oxidative stress and neuro-inflammation, substantial evidence now indicates that LDR can mitigate tissue damage through antioxidant defenses. Although adult neurogenesis has been reported to be beneficial for the regeneration of nervous system, some studies demonstrate that neurogenesis increases in AD brains. In spite of these reports, cellular therapy is introduced as a promising strategy for AD, and hence, LDR can affect the proliferation and differentiation of neural stem cells. Although such mechanisms are not fully known yet, it is hoped

  13. A model of cardiovascular disease giving a plausible mechanism for the effect of fractionated low-dose ionizing radiation exposure.

    Directory of Open Access Journals (Sweden)

    Mark P Little

    2009-10-01

    Full Text Available Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease at low radiation doses in various occupationally exposed groups receiving small daily radiation doses. Assuming that they are causal, the mechanisms for effects of chronic fractionated radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for atherosclerosis and perform stability analysis, based wherever possible on human data. We show that a predicted consequence of multiple small radiation doses is to cause mean chemo-attractant (MCP-1 concentration to increase linearly with cumulative dose. The main driver for the increase in MCP-1 is monocyte death, and consequent reduction in MCP-1 degradation. The radiation-induced risks predicted by the model are quantitatively consistent with those observed in a number of occupationally-exposed groups. The changes in equilibrium MCP-1 concentrations with low density lipoprotein cholesterol concentration are also consistent with experimental and epidemiologic data. This proposed mechanism would be experimentally testable. If true, it also has substantive implications for radiological protection, which at present does not take cardiovascular disease into account. The Japanese A-bomb survivor data implies that cardiovascular disease and cancer mortality contribute similarly to radiogenic risk. The major uncertainty in assessing the low-dose risk of cardiovascular disease is the shape of the dose response relationship, which is unclear in the Japanese data. The analysis of the present paper suggests that linear extrapolation would be appropriate for this endpoint.

  14. Age and Chronicity of Administration Dramatically Influenced the Impact of Low Dose Paraquat Exposure on Behavior and Hypothalamic-Pituitary-Adrenal Activity

    Directory of Open Access Journals (Sweden)

    Chris A. Rudyk

    2017-07-01

    Full Text Available Little is known of the age-dependent and long-term consequences of low exposure levels of the herbicide and dopaminergic toxicant, paraquat. Thus, we assessed the dose-dependent effects of paraquat using a typical short-term (3 week exposure procedure, followed by an assessment of the effects of chronic (16 weeks exposure to a very low dose (1/10th of what previously induced dopaminergic neuronal damage. Short term paraquat treatment dose-dependently induced deficits in locomotion, sucrose preference and Y-maze performance. Chronic low dose paraquat treatment had a very different pattern of effects that were also dependent upon the age of the animal: in direct contrast to the short-term effects, chronic low dose paraquat increased sucrose consumption and reduced forced swim test (FST immobility. Yet these effects were age-dependent, only emerging in mice older than 13 months. Likewise, Y-maze spontaneous alternations and home cage activity were dramatically altered as a function of age and paraquat chronicity. In both the short and long-term exposure studies, increased corticosterone and altered hippocampal glucocorticoid receptor (GR levels were induced by paraquat, but surprisingly these effects were blunted in the older mice. Thus, paraquat clearly acts as a systemic stressor in terms of corticoid signaling and behavioral outcomes, but that paradoxical effects may occur with: (a repeated exposure at; (b very low doses; and (c older age. Collectively, these data raise the possibility that repeated “hits” with low doses of paraquat in combination with aging processes might have promoted compensatory outcomes.

  15. Exposure to low doses (20 cGy) of Hze results in spatial memory impairment in rats.

    Science.gov (United States)

    Britten, Richard; Johnson, Angela; Davis, Leslie; Green-Mitchell, Shamina; Chabriol, Olivia; Sanford, Larry; Drake, Richard

    Escape hole over the 5 days of training. There was a suggestion that there may be some recovery in spatial memory performance by 6 months post exposure. Our preliminary data on Hze-induced exposure on sleep, suggests that within 4 weeks of Hze exposure there is a change in sleep latency, raising the possibility that some of the observed decline in neurocognitive performance may arise due to perturbed sleep patterns. We have used MALDI-IMS to determine the Hze-induced changes in the neuroproteome with a high degree of spatial resolution. Using this technique we have found that a peptide with a m/z of 14207 is differentially elevated in the Thalamus of irradiated rats that have good spatial memory. MALDI-MSI thus appears to be a powerful tool that can be used to identify radiation-induced changes in ancillary brain regions that correlate with neurocognitive impairment, and will ultimately be useful for identifying proteins whose expression changes in parallel with Hze-induced neurocognitive deficits. SUMMARY. We have found that mission-relevant Hze doses (20 cGy) lead to significant neu-rocognitive defects. Clearly such low doses of Hze are unlikely to lead to a significant loss of neuronal cells, and have not been reported to lead to gliosis etc. We take this as further evi-dence that neurocognitive impairment is not solely dependent upon radiation-induced changes in neurogenesis and neuronal cell death. FUNDING: The authors gratefully acknowledge grant support from NASA (NNJ06HD89D).

  16. Exposure to low dose benzo[a]pyrene during early life stages causes symptoms similar to cardiac hypertrophy in adult zebrafish.

    Science.gov (United States)

    Huang, Lixing; Gao, Dongxu; Zhang, Youyu; Wang, Chonggang; Zuo, Zhenghong

    2014-07-15

    Growing evidence indicates that polycyclic aromatic hydrocarbons (PAHs) can lead to cardiac hypertrophy and recent research indicates that exposure to low dose crude oil during early embryonic development may lead to impacts on heart health at later life stages. The aim of this study was to evaluate whether exposure during early life stages to low dose benzo[a]pyrene (BaP), as a high-ring PAH, would lead to cardiac hypertrophy at later life stages. Zebrafish were exposed to low dose BaP until 96 hpf, then transferred to clean water and maintained for a year before histological and molecular biological analysis. Our results showed that exposure to low level BaP during early life stages increased heart weight to body weight ratios and deposited collagen in the heart of adult zebrafish. ANP, BNP and c-Myc were also induced in the heart of adult zebrafish by BaP. These results proved that low level BaP exposure during early life stages caused symptoms similar to cardiac hypertrophy in adult zebrafish. Our results displayed an elevated expression of CdC42, RhoA, p-ERK1, 2 and Rac1. Therefore, the mechanism of the cardiac hypertrophy caused by BaP exposure during early life stages may be through inducing the expression of CdC42, RhoA and Rac1, together with activating ERK1, 2. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Radiation-induced bystander effects in the Atlantic salmon (salmo salar L.) following mixed exposure to copper and aluminum combined with low-dose gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mothersill, Carmel; Seymour, Colin B. [McMaster University, Medical Physics and Applied Radiation Sciences Department, Hamilton, ON (Canada); Norwegian University of Life Sciences, Department of Plant and Environmental Sciences, Aas (Norway); Smith, Richard W. [McMaster University, Medical Physics and Applied Radiation Sciences Department, Hamilton, ON (Canada); Heier, Lene Soerlie; Teien, Hans-Christian; Land, Ole Christian; Oughton, Deborah; Salbu, Brit [Norwegian University of Life Sciences, Department of Plant and Environmental Sciences, Aas (Norway)

    2014-03-15

    Very little is known about the combined effects of low doses of heavy metals and radiation. However, such ''multiple stressor'' exposure is the reality in the environment. In the work reported in this paper, fish were exposed to cobalt 60 gamma irradiation with or without copper or aluminum in the water. Doses of radiation ranged from 4 to 75 mGy delivered over 48 or 6 h. Copper doses ranged from 10 to 80 μg/L for the same time period. The aluminum dose was 250 μg/L. Gills and skin were removed from the fish after exposure and explanted in tissue culture flasks for investigation of bystander effects of the exposures using a stress signal reporter assay, which has been demonstrated to be a sensitive indicator of homeostatic perturbations in cells. The results show complex synergistic interactions of radiation and copper. Gills on the whole produce more toxic bystander signals than skin, but the additivity scores show highly variable results which depend on dose and time of exposure. The impacts of low doses of copper and low doses of radiation are greater than additive, medium levels of copper alone have a similar level of effect of bystander signal toxicity to the low dose. The addition of radiation stress, however, produces clear protective effects in the reporters treated with skin-derived medium. Gill-derived medium from the same fish did not show protective effects. Radiation exposure in the presence of 80 μg/L led to highly variable results, which due to animal variation were not significantly different from the effect of copper alone. The results are stressor type, stressor concentration and time dependent. Clearly co-exposure to radiation and heavy metals does not always lead to simple additive effects. (orig.)

  18. Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel.

    Science.gov (United States)

    Kwon, Jee Young; Weon, Jong-Il; Koedrith, Preeyaporn; Park, Kang-Sik; Kim, Im Soon; Seo, Young Rok

    2013-09-01

    Cadmium and nickel have been classified as carcinogenic to humans by the World Health Organization's International Agency for Research on Cancer. Given their prevalence in the environment, the fact that cadmium and nickel may cause diseases including cancer even at low doses is a cause for concern. However, the exact mechanisms underlying the toxicological effects induced by low-dose exposure to cadmium and nickel remain to be elucidated. Furthermore, it has recently been recognized that integrative analysis of DNA, mRNA and proteins is required to discover biomarkers and signaling networks relevant to human toxicant exposure. In the present study, we examined the deleterious effects of chronic low-dose exposure of either cadmium or nickel on global profiling of DNA copy number variation, mRNA and proteins. Array comparative genomic hybridization, gene expression microarray and functional proteomics were conducted, and a bioinformatics tool, which predicted signaling pathways, was applied to integrate data for each heavy metal separately and together. We found distinctive signaling networks associated with subchronic low-dose exposure to cadmium and nickel, and identified pathways common to both. ACTB, HSP90AA1, HSPA5 and HSPA8, which are key mediators of pathways related to apoptosis, proliferation and neoplastic processes, were key mediators of the same pathways in low-dose nickel and cadmium exposure in particular. CASP-associated signaling pathways involving CASP3, CASP7 and CASP9 were observed in cadmium-exposed cells. We found that HSP90AA1, one of the main modulators, interacted with HIF1A, AR and BCL2 in nickel-exposed cells. Interestingly, we found that HSP90AA1 was involved in the BCL2-associated apoptotic pathway in the nickel-only data, whereas this gene interacted with several genes functioning in CASP-associated apoptotic signaling in the cadmium-only data. Additionally, JUN and FASN were main modulators in nickel-responsive signaling pathways. Our

  19. Exposure to low doses of 137cesium and nicotine during postnatal development modifies anxiety levels, learning, and spatial memory performance in mice.

    Science.gov (United States)

    Bellés, Montserrat; Heredia, Luis; Serra, Noemí; Domingo, José L; Linares, Victoria

    2016-11-01

    Radiation therapy is a major cause of long-term complications observed in survivors of pediatric brain tumors. However, the effects of low-doses of ionizing radiation (IR) to the brain are less studied. On the other hand, tobacco is one of the most heavily abused drugs in the world. Tobacco is not only a health concern for adults. It has also shown to exert deleterious effects on fetuses, newborns, children and adolescents. Exposure to nicotine (Nic) from smoking may potentiate the toxic effects induced by IR on brain development. In this study, we evaluated in mice the cognitive effects of concomitant exposure to low doses of internal radiation ( 137 Cs) and Nic during neonatal brain development. On postnatal day 10 (PND10), two groups of C57BL/6J mice were subcutaneously exposed to 137-Cesium ( 137 Cs) (4000 and 8000 Bq/kg) and/or Nic (100 μg/ml). At the age of two months, neurobehavior of mice was assessed. Results showed that exposure to IR-alone or in combination with Nic-increased the anxiety-like of the animals without changing the activity levels. Moreover, exposure to IR impaired learning and spatial memory. However, Nic administration was able to reverse this effect, but only at the low dose of 137 Cs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Atomic structure from large-area, low-dose exposures of materials: A new route to circumvent radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, J.C., E-mail: jannik.meyer@univie.ac.at; Kotakoski, J.; Mangler, C.

    2014-10-15

    Beam-induced structural modifications are a major nuisance in the study of materials by high-resolution electron microscopy. Here, we introduce a new approach to circumvent the radiation damage problem by a statistical treatment of large, noisy, low-dose data sets of non-periodic configurations (e.g. defects) in the material. We distribute the dose over a mixture of different defect structures at random positions and with random orientations, and recover representative model images via a maximum likelihood search. We demonstrate reconstructions from simulated images at such low doses that the location of individual entities is not possible. The approach may open a route to study currently inaccessible beam-sensitive configurations. - Highlights: • A new approach to circumvent radiation damage. • Statistical treatment of large noisy data sets. • Analysis of radiation sensitive material defects.

  1. Risk management or mind control? Possible messages in the report by the working group on the risk management of low-dose exposures

    International Nuclear Information System (INIS)

    Onai, Takayuki; Shirabe, Masashi

    2012-01-01

    Fukushima accident discharged a large amount of radioactive materials to the air and brought about a long-term low-dose radiation exposure risk in contaminated area. In December 2011 the government working group (WG) on the risk management of low-dose radiation exposure issued the report on subjects: (1) health effects from annual radiation exposure of 20 mSv, (2) special consideration necessary for children and pregnant women and (3) proper way communicating citizens on radioactive materials and radiation doses in relation to health risks from low-dose radiation exposure. This article recommended making radiation protection strategies based on discussions among experts, government and citizens in consideration of “uncertainty” of scientific knowledge, and it criticized the WG's report mainly in the following respects. 1) The report mixed evacuation order level and ICRP's reference level in its discussion on “20 mSv”. 2) It was over-optimistic and frequently misleading on health risks of low-dose radiation. For example, it sometimes discussed the risks employing data and knowledge against recommendations of international authorities like UNSCEAR and ICRP. 3) It regarded Fukushima residents’ anxieties and stresses to be controlled as the only source of health risks. This attitude offered a counterpoint to UNSCEAR's deliberate attitude to “radiophobia”. 4) Against the spirit of ICRP Publ.111, only experts of WG made decisions about radiation protection in the absence of stakeholders. As its result, 5) risk communication recommended in the report was not interactive, in fact, based on “deficit model” of science communication. (author)

  2. Defence strategies and antibiotic resistance gene abundance in enterococci under stress by exposure to low doses of peracetic acid.

    Science.gov (United States)

    Turolla, Andrea; Sabatino, Raffaella; Fontaneto, Diego; Eckert, Ester M; Colinas, Noemi; Corno, Gianluca; Citterio, Barbara; Biavasco, Francesca; Antonelli, Manuela; Mauro, Alessandro; Mangiaterra, Gianmarco; Di Cesare, Andrea

    2017-10-01

    Peracetic acid (PAA) is an organic compound used efficiently as disinfectant in wastewater treatments. Yet, at low doses it may cause selection; thus, the effect of low doses of PAA on Enterococcus faecium as a proxy of human-related microbial waste was evaluated. Bacteria were treated with increasing doses of PAA (from 0 to 25 mg L -1 min) and incubated in regrowth experiments under non-growing, limiting conditions and under growing, favorable conditions. The changes in bacterial abundance, in bacterial phenotype (number and composition of small cell clusters), and in the abundance of an antibiotic resistance gene (ARG) was evaluated. The experiment demonstrated that the selected doses of PAA efficiently removed enterococci, and induced a long-lasting effect after PAA inactivation. The relative abundance of small clusters increased during the experiment when compared with that of the inoculum. Moreover, under growing favorable conditions the relative abundance of small clusters decreased and the number of cells per cluster increased with increasing PAA doses. A strong stability of the measured ARG was found, not showing any effect during the whole experiment. The results demonstrated the feasibility of low doses of PAA to inactivate bacteria. However, the stress induced by PAA disinfection promoted a bacterial adaptation, even if potentially without affecting the abundance of the ARG. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice

    Science.gov (United States)

    Yu, Kanglun; Doherty, Alison H.; Genik, Paula C.; Gookin, Sara E.; Roteliuk, Danielle M.; Wojda, Samantha J.; Jiang, Zhi-Sheng; McGee-Lawrence, Meghan E.; Weil, Michael M.; Donahue, Seth W.

    2017-11-01

    During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation.

  4. Does the amount of tagged stool and fluid significantly affect the radiation exposure in low-dose CT colonography performed with an automatic exposure control?

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyun Kyong; Lee, Kyoung Ho; Kim, So Yeon; Kim, Young Hoon [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Seoul National University College of Medicine, Seoul National University Medical Research Center, Institute of Radiation Medicine, Bundang (Korea, Republic of); Kim, Kil Joong [Seoul National University College of Medicine, Department of Radiation Applied Life Science, Seoul (Korea, Republic of); Kim, Bohyoung; Lee, Hyunna [Seoul National University, School of Computer Science and Engineering, Seoul (Korea, Republic of); Park, Seong Ho [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Yanof, Jeffrey H. [Philips Healthcare, CT Clinical Science, Cleveland, OH (United States); Hwang, Seung-sik [Inha University School of Medicine, Department of Social and Preventive Medicine, Incheon (Korea, Republic of)

    2011-02-15

    To determine whether the amount of tagged stool and fluid significantly affects the radiation exposure in low-dose screening CT colonography performed with an automatic tube-current modulation technique. The study included 311 patients. The tagging agent was barium (n = 271) or iodine (n = 40). Correlation was measured between mean volume CT dose index (CTDI{sub vol}) and the estimated x-ray attenuation of the tagged stool and fluid (ATT). Multiple linear regression analyses were performed to determine the effect of ATT on CTDI{sub vol} and the effect of ATT on image noise while adjusting for other variables including abdominal circumference. CTDI{sub vol} varied from 0.88 to 2.54 mGy. There was no significant correlation between CTDI{sub vol} and ATT (p = 0.61). ATT did not significantly affect CTDI{sub vol} (p = 0.93), while abdominal circumference was the only factor significantly affecting CTDI{sub vol} (p < 0.001). Image noise ranged from 59.5 to 64.1 HU. The p value for the regression model explaining the noise was 0.38. The amount of stool and fluid tagging does not significantly affect radiation exposure. (orig.)

  5. Does the amount of tagged stool and fluid significantly affect the radiation exposure in low-dose CT colonography performed with an automatic exposure control?

    International Nuclear Information System (INIS)

    Lim, Hyun Kyong; Lee, Kyoung Ho; Kim, So Yeon; Kim, Young Hoon; Kim, Kil Joong; Kim, Bohyoung; Lee, Hyunna; Park, Seong Ho; Yanof, Jeffrey H.; Hwang, Seung-sik

    2011-01-01

    To determine whether the amount of tagged stool and fluid significantly affects the radiation exposure in low-dose screening CT colonography performed with an automatic tube-current modulation technique. The study included 311 patients. The tagging agent was barium (n = 271) or iodine (n = 40). Correlation was measured between mean volume CT dose index (CTDI vol ) and the estimated x-ray attenuation of the tagged stool and fluid (ATT). Multiple linear regression analyses were performed to determine the effect of ATT on CTDI vol and the effect of ATT on image noise while adjusting for other variables including abdominal circumference. CTDI vol varied from 0.88 to 2.54 mGy. There was no significant correlation between CTDI vol and ATT (p = 0.61). ATT did not significantly affect CTDI vol (p = 0.93), while abdominal circumference was the only factor significantly affecting CTDI vol (p < 0.001). Image noise ranged from 59.5 to 64.1 HU. The p value for the regression model explaining the noise was 0.38. The amount of stool and fluid tagging does not significantly affect radiation exposure. (orig.)

  6. Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after low dose exposure to arsenite

    International Nuclear Information System (INIS)

    Sykora, Peter; Snow, Elizabeth T.

    2008-01-01

    Base excision repair (BER) is crucial for development and for the repair of endogenous DNA damage. However, unlike nucleotide excision repair, the regulation of BER is not well understood. Arsenic, a well-established human carcinogen, is known to produce oxidative DNA damage, which is repaired primarily by BER, whilst high doses of arsenic can also inhibit DNA repair. However, the mechanism of repair inhibition by arsenic and the steps inhibited are not well defined. To address this question we have investigated the regulation of DNA polymerase β (Pol β) and AP endonuclease (APE1), in response to low, physiologically relevant doses of arsenic. GM847 lung fibroblasts and HaCaT keratinocytes were exposed to sodium arsenite, As(III), and mRNA, protein levels and BER activity were assessed. Both Pol β and APE1 mRNA exhibited significant dose-dependant down regulation at doses of As(III) above 1 μM. However, at lower doses Pol β mRNA and protein levels, and consequently, BER activity were significantly increased. In contrast, APE1 protein levels were only marginally increased by low doses of As(III) and there was no correlation between APE1 and overall BER activity. Enzyme supplementation of nuclear extracts confirmed that Pol β was rate limiting. These changes in BER correlated with overall protection against sunlight UV-induced toxicity at low doses of As(III) and produced synergistic toxicity at high doses. The results provide evidence that changes in BER due to low doses of arsenic could contribute to a non-linear, threshold dose response for arsenic carcinogenesis

  7. Progress in structure recovery from low dose exposures: Mixed molecular adsorption, exploitation of symmetry and reconstruction from the minimum signal level

    Energy Technology Data Exchange (ETDEWEB)

    Kramberger, C., E-mail: Christian.Kramberger-Kaplan@univie.ac.at; Meyer, J.C., E-mail: Jannik.Meyer@univie.ac.at

    2016-11-15

    We investigate the recovery of structures from large-area, low dose exposures that distribute the dose over many identical copies of an object. The reconstruction is done via a maximum likelihood approach that does neither require to identify nor align the individual particles. We also simulate small molecular adsorbates on graphene and demonstrate the retrieval of images with atomic resolution from large area and extremely low dose raw data. Doses as low as 5 e{sup −}/Å{sup 2} are sufficient if all symmetries (translations, rotations and mirrors) of the supporting membrane are exploited to retrieve the structure of individual adsorbed molecules. We compare different optimization schemes, consider mixed molecules and adsorption sites, and requirements on the amount of data. We further demonstrate that the maximum likelihood approach is only count limited by requiring at least three independent counts per entity. Finally, we demonstrate that the approach works with real experimental data and in the presence of aberrations.

  8. Effects of perinatal exposure to low doses of tributyltin chloride on pregnancy outcome and postnatal development in mouse offspring.

    Science.gov (United States)

    Si, Jiliang; Li, Jie; Zhang, Fengmei; Li, Guozhen; Xin, Quanbin; Dai, Bingqin

    2012-10-01

    Tributyltin (TBT), an endocrine-disrupting chemical, is well known to induce imposex in female gastropods. In this study, we assessed the effects of low doses of tributyltin chloride (TBTCl) on dams and their offspring. Pregnant mice were administered by gavage with 0, 1, 10, or 100 μg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. There were no TBT treatment-related deaths or clinical signs of toxicity for dams, and no treatment-related effects on body weight, litter sizes, gestational length of dams, and sex ratio, lactational body weight, postnatal survival, age at eruption of incisors, and eye opening of pups. However, at 100 μg/kg, TBTCl retarded the testes descent of male offspring. Behavioral tests showed a significant delay in cliff-drop aversion response in offspring of 10 and 100 μg/kg groups, but no significant difference in the righting reflex between control and TBT-exposed offspring was detectable. These results indicate that neurobehavioral toxicity seems to be one sensitive indicator to assess the risk of low doses of TBT. Copyright © 2011 Wiley Periodicals, Inc.

  9. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V.; Ershova, Liza S. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Osipov, Andrian N. [Federal Medial and Biological Center named after Burnazyan of the Federal Medical and Biological Agency (FMBTz named after Burnazyan of FMBA), Moscow (Russian Federation); State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya, 46, Moscow, 123098 (Russian Federation); Zhuravleva, Veronika F.; Pankratova, Galina V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N.; Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation)

    2015-09-15

    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  10. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Olga Loseva

    2014-07-01

    Full Text Available The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR exposure (5 or 15 mGy/h of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

  11. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: Effects of epinephrine and oxygen therapies

    Energy Technology Data Exchange (ETDEWEB)

    Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G.; Xu, Fadi; Russell, Robert G.; Sopori, Mohan L., E-mail: msopori@lrri.org

    2014-01-15

    Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes including weakened response to hypoxia. We now show that LD{sub 50} sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24 h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD{sub 50} sarin-exposed animals were administered the bronchodilator epinephrine, > 90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD{sub 50} sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin. - Highlights: • Inhalation exposure of rats to LD{sub 50} sarin causes death through respiratory failure. • Severe bronchoconstriction is the major cause of sarin-induced respiratory failure. • Transfer of sarin exposed rats to 60% oxygen improves the mortality temporarily.

  12. DNA methylation and potential multigenerational epigenetic effects linked to uranium chronic low-dose exposure in gonads of males and females rats.

    Science.gov (United States)

    Elmhiri, G; Gloaguen, C; Grison, S; Kereselidze, D; Elie, C; Tack, K; Benderitter, M; Lestaevel, P; Legendre, A; Souidi, M

    2018-01-05

    An increased health problem in industrialised countries is the contemporary concern of public and scientific community as well. This has been attributed in part to accumulated environmental pollutants especially radioactive substances and the use of nuclear power plants worldwide. However, the outcome of chronic exposure to low doses of a radionuclide such as uranium remains unknown. Recently, a paradigm shift in the perception of risk of radiotoxicology has emerged through investigating the possibility of transmission of biological effects over generations, in particular by epigenetic pathways. These processes are known for their crucial roles associated with the development of several diseases. The current work investigates the epigenetic effect of chronic exposure to low doses of uranium and its inheritance across generations. Materials and Methods To test this proposition, a rodent multigenerational model, males and females, were exposed to a non-toxic concentration of uranium (40mgL -1 drinking water) for nine months. The uranium effects on were evaluated over three generations (F0, F1 and F2) by analysing the DNA methylation profile and DNMT genes expression in ovaries and testes tissues. Here we report a significant hypermethylation of testes DNA (p <0.005) whereas ovaries showed hypomethylated DNA (p <0.005). Interestingly, this DNA methylation profile was significantly maintained across generations F0, F1 and F2. Furthermore, qPCR results of both tissues imply a significant change in the expression of DNA methyltransferase genes (DNMT 1 and DNMT3a/b) as well. Altogether, our work demonstrates for the first time a sex-dependance and inheritance of epigenetic marks, DNA methylation, as a biological response to the exposure to low doses of uranium. However, it is not clear which type of reproductive cell type is more responsive in this context. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Metabonomic analysis of urine from rats after low-dose exposure to 3-chloro-1,2-propanediol using UPLC-MS.

    Science.gov (United States)

    Liu, Liyan; He, Yujie; Lu, Huimin; Wang, Maoqing; Sun, Changhao; Na, Lixin; Li, Ying

    2013-05-15

    To study the toxic effect of chronic exposure to 3-chloro-1,2-propanediol (3-MCPD) at low doses, a metabonomics approach based on ultrahigh-performance liquid chromatography and quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was performed. Two different doses of 3-MCPD (1.1 and 5.5mg/kg bw/d) were administered to Wistar rats for 120 days (1.1mg/kg bw/d: lowest observed adverse effect level [LOAEL]). The metabolite profiles and biochemical parameters were obtained at five time points after treatment. For the 3-MCPD-treated groups, a significant change in urinary N-acetyl-β-d-glucosaminidase and β-d-galactosidase was detected on day 90, while some biomarkers based on the metabonomics, such as N-acetylneuraminic acid, N-acetyl-l-tyrosine, and gulonic acid, were detected on day 30. These results suggest that these biomarkers changed more sensitively and earlier than conventional biochemical parameters and were thus considered early and sensitive biomarkers of exposure to 3-MCPD; these biomarkers provide more information on toxicity than conventional biochemical parameters. These results might be helpful to investigate the toxic mechanisms of 3-MCPD and provide a scientific basis for assessing the effect of chronic exposure to low-dose 3-MCPD on human health. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  14. Health effects of low dose exposures to external ionizing radiation in the French cohort of nuclear workers CEA-AREVA-EDF - 5287

    International Nuclear Information System (INIS)

    Leuraud, K.; Fournier, L.; Samson, E.; Caer-Lorho, S.; Laurier, D.; Laroche, P.; Le Guen, B.

    2015-01-01

    Populations of nuclear workers are particularly relevant to study health effects of low dose and low dose-rate exposures to ionizing radiation. In France, a cohort of nuclear workers employed by CEA, AREVA NC, or EDF, and badge-monitored for radiation exposure, has been followed-up. Annual exposure to penetrating photons was reconstructed for each worker. Standardized mortality ratios were calculated using national mortality rates as the reference. Estimates of radiation dose-mortality associations were obtained using a linear excess relative risk (ERR) model. A total of 59,004 workers were followed-up between 1968 and 2004, for an average of 25 years. The mean cumulative photons dose was 16.1 mSv. At the end of the follow-up, workers were 56 years old and 6,310 workers had died. A strong healthy worker effect was observed. Positive but imprecise estimates of ERR/Sv were observed for all solid cancers and leukemia excluding chronic lymphocytic leukemia. A significant ERR/Sv was found for myeloid leukemia. This cohort study is the most informative ever conducted in France among nuclear workers. Results confirmed a healthy worker effect due to selection at hiring and health monitoring from occupational medicine. Observed dose-risk relationships were consistent with risks estimated in other studies, even if they remained associated to a large uncertainty. (authors)

  15. Exposure to perfluorononanoic acid combined with a low-dose mixture of 14 human-relevant compounds disturbs energy/lipid homeostasis in rats

    DEFF Research Database (Denmark)

    Skov, Kasper; Kongsbak, Kristine Grønning; Hadrup, Niels

    2015-01-01

    , whereas effects on lipid metabolism in the liver were mainly driven by PFNA. This study verifies that a chemical mixture given at high-end human exposure levels can affect lipid homeostasis and that the combined use of metabolomics and transcriptomics can provide complimentary information allowing......Humans are constantly exposed to a significant number of compounds and many are readily detected in human body fluids. Worryingly, several of these compounds are either suspected to be, or have already been shown to be harmful to humans either individually or in combination. However, the potential...... consequences of low-dose exposure to complex mixtures remain poorly understood. We have profiled the effects on rat blood plasma and liver homeostasis using metabolomics and transcriptomics following 2-week exposure to either a mixture of 14 common chemicals (Mix), perfluorononanoic acid (PFNA) at low (0...

  16. Low Dose Risk, Decisions, and Risk Communication

    International Nuclear Information System (INIS)

    Flynn, James

    2002-01-01

    The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation

  17. Bystander effects of exposure to low-dose-rate 125I seeds on human lung cancers cells in vitro

    International Nuclear Information System (INIS)

    Jia Rongfei; Chen Honghong; Yu Lei; Zhao Meijia; Shao Chunlin; Cheng Wenying

    2007-01-01

    The bystander effects induced by continuous low-dose-rate (LDR) 125 I seeds radiation on damage of human lung cancer cells were investigated. Human adenocarcinoma cell line A549 and human small cell lung cancer cell line NCI-H446, which have different sensitivities to high-dose rate (HDR) external irradiation, were exposed directly to 125 I seeds in vitro and co-cultured with unirradiated cells for 24 h. Using cytokinesis-blocking micronucleus method and γ H2AX fluorescence immunoassay, bystander effects induced by 2Gy and 4Gy 125 I seed irradiation on micronucleus formation and DNA double-strand breaks (DSBs) of human lung cancer cells were detected and evaluated. The results showed that irradiation with 125 I seeds can induce medium-mediated bystander effects in A549 cells and NCI-H446 cells, exhibiting that both micronuclei formation and γ H2AX focus formation in bystander cells were increased significantly compared with non-irradiated cells. The extent of DNA damage induced by bystander effects was correlated with accumulated radiation dose and radiosensitive of tumor cells. NCI-H446 cells that were sensitive to HDR γ irradiation were more sensitive to continuous LDR irradiation and bystander effects than A549. However, a comparison between the bystander effects and direct effects elicits the intensity of bystander responses of A549 cells was higher than that of NCI-H446 cells. A dose-related reduction in bystander responses was observed both in A549 cells and NCI-H446 cells, suggesting that the signaling factors involved in the bystander signaling pathways may decrease with the increase of cell damages. (authors)

  18. Effects of low-level sarin and cyclosarin exposure and Gulf War Illness on brain structure and function: a study at 4T.

    Science.gov (United States)

    Chao, Linda L; Abadjian, Linda; Hlavin, Jennifer; Meyerhoff, Deiter J; Weiner, Michael W

    2011-12-01

    More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Persian Gulf War (GW). We previously found reduced total gray matter (GM) volume in 40 GW veterans with suspected GB/GF exposure relative to 40 matched, unexposed GW veterans on a 1.5T MR scanner. In this study, we reexamine the relationship between GB/GF exposure and volumetric measurements of gross neuroanatomical structures in a different cohort of GW veterans on a 4T MR scanner. Neuropsychological and magnetic resonance imaging (MRI) data from a cross sectional study on Gulf War Illness performed between 2005 and 2010 were used in this study. 4T MRI data were analyzed using automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Binary comparisons of 64 GB/GF exposed veterans and 64 'matched', unexposed veterans revealed reduced GM (p=0.03) and WM (p=0.03) volumes in the exposed veterans. Behaviorally, exposed veterans committed more errors of omission (p=0.02) and tended to have slower responses (p=0.05) than unexposed veterans on the Continuous Performance Test (CPT), a measure sustained and selective attention. Regression analyses confirmed that GB/GF exposure status predicted GM (β=-0.11, p=0.02) and WM (β=-0.14, p=0.03) volumes, and number of CPT omission errors (β=0.22, p=0.02) over and above potentially confounding demographic, clinical, and psychosocial variables. There was no dose-response relationship between estimated levels of GB/GF exposure and brain volume. However, we did find an effect of Gulf War Illness/Chronic Multisymptom Illness on both GM and WM volume in the GB/GF exposed veterans. These findings confirm previous reports by our group and others of central nervous system pathology in GW veterans with suspected exposure to low levels of GB/GF two decades after the

  19. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis.

    Science.gov (United States)

    Hu, Zhiwei; Brooks, Samira A; Dormoy, Valérian; Hsu, Chia-Wen; Hsu, Hsue-Yin; Lin, Liang-Tzung; Massfelder, Thierry; Rathmell, W Kimryn; Xia, Menghang; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Brown, Dustin G; Prudhomme, Kalan R; Colacci, Annamaria; Hamid, Roslida A; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P; Woodrick, Jordan; Scovassi, A Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K; Lowe, Leroy; Jensen, Lasse; Bisson, William H; Kleinstreuer, Nicole

    2015-06-01

    One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Influence of chitosan and melanin-glucan complex onto gamma-exposure with low doses and acute stressful reaction

    International Nuclear Information System (INIS)

    Senyuk, O.F.; Tarasenko, P.D.; Pazukhin, Eh.M.; Gorovoj, L.F.; Varlamov, V.P.

    2004-01-01

    Possibilities of prevention and reduction of consequences of acute exposure on the background of immobilization stress with the help of chitosan preparations and of melanin - glucan complex of highest bazidiomicetes (fungi) were studied. Tested preparations were capable to protect hematological and immunological homeostasis of line BALB/c mice from stressful reaction provoked by acute exposure and two-hour immobilization. The most expressed normalizing and adapting effect had the mixture composed of chitosan and melanin-glucan complex

  1. Low-dose dose-response for reduced cell viability after exposure of human keratinocyte (HEK001 cells to arsenite

    Directory of Open Access Journals (Sweden)

    Kenneth T. Bogen

    Full Text Available The in vitro arsenite (AsIII cytotoxicity dose-response (DR of human keratinocytes (HEK001 was examined at greater statistical resolution than ever previously reported using the MTT assay to determine cell viability. Fifty-four 96-well plates were treated with AsIII concentrations of 0.25, 0.5, 1, 2, 3, 4, 5, 7, 10, 15, 20, 25, or 30 μM. Because of unexpected variation in viability response patterns, a two-stage DR analysis was used in which data on plate-specific viability (%, estimated as 100% times the ratio of measured viability in exposed to unexposed cells, were fit initially to a generalized lognormal response function positing that HEK001 cells studied consisted of: a proportion P of relatively highly sensitive (HS cells, a proportion Po of relatively resistant cells, and a remaining (1–P–Po fraction of typical-sensitivity (TS cells exhibiting the intermediate level of AsIII sensitivity characteristic of most cells in each assay. The estimated fractions P and Po were used to adjust data from all 54 plates (and from the 28 plates yielding the best fits to reflect the condition that P = Po = 0 to provide detailed DR analysis specifically for TS cells. Four DR models fit to the combined adjusted data were each very predictive (R2 > 0.97 overall but were inconsistent with at least one of the data set examined (p  0.30 and exceeded 100% significance (p ≤ 10−6. A low-dose hormetic model provided the best fit to the combined adjusted data for TS cells (R2 = 0.995. Marked variability in estimates of P (the proportion of apparent HS cells was unexpected, not readily explained, and warrants further study using additional cell lines and assay methods, and in vivo. Keywords: Arsenic, Arsenate, Cell culture, Cell death, Cytotoxicity, HEK001 cells

  2. Impact of low dose prenatal ethanol exposure on glucose homeostasis in Sprague-Dawley rats aged up to eight months.

    Directory of Open Access Journals (Sweden)

    Megan E Probyn

    Full Text Available Excessive exposure to alcohol prenatally has a myriad of detrimental effects on the health and well-being of the offspring. It is unknown whether chronic low-moderate exposure of alcohol prenatally has similar and lasting effects on the adult offspring's health. Using our recently developed Sprague-Dawley rat model of 6% chronic prenatal ethanol exposure, this study aimed to determine if this modest level of exposure adversely affects glucose homeostasis in male and female offspring aged up to eight months. Plasma glucose concentrations were measured in late fetal and postnatal life. The pancreas of 30 day old offspring was analysed for β-cell mass. Glucose handling and insulin action was measured at four months using an intraperitoneal glucose tolerance test and insulin challenge, respectively. Body composition and metabolic gene expression were measured at eight months. Despite normoglycaemia in ethanol consuming dams, ethanol-exposed fetuses were hypoglycaemic at embryonic day 20. Ethanol-exposed offspring were normoglycaemic and normoinsulinaemic under basal fasting conditions and had normal pancreatic β-cell mass at postnatal day 30. However, during a glucose tolerance test, male ethanol-exposed offspring were hyperinsulinaemic with increased first phase insulin secretion. Female ethanol-exposed offspring displayed enhanced glucose clearance during an insulin challenge. Body composition and hepatic, muscle and adipose tissue metabolic gene expression levels at eight months were not altered by prenatal ethanol exposure. Low-moderate chronic prenatal ethanol exposure has subtle, sex specific effects on glucose homeostasis in the young adult rat. As aging is associated with glucose dysregulation, further studies will clarify the long lasting effects of prenatal ethanol exposure.

  3. Changes in the Metabolome in Response to Low-Dose Exposure to Environmental Chemicals Used in Personal Care Products during Different Windows of Susceptibility.

    Science.gov (United States)

    Houten, Sander M; Chen, Jia; Belpoggi, Fiorella; Manservisi, Fabiana; Sánchez-Guijo, Alberto; Wudy, Stefan A; Teitelbaum, Susan L

    2016-01-01

    The consequences of ubiquitous exposure to environmental chemicals remain poorly defined. Non-targeted metabolomic profiling is an emerging method to identify biomarkers of the physiological response to such exposures. We investigated the effect of three commonly used ingredients in personal care products, diethyl phthalate (DEP), methylparaben (MPB) and triclosan (TCS), on the blood metabolome of female Sprague-Dawley rats. Animals were treated with low levels of these chemicals comparable to human exposures during prepubertal and pubertal windows as well as chronically from birth to adulthood. Non-targeted metabolomic profiling revealed that most of the variation in the metabolites was associated with developmental stage. The low-dose exposure to DEP, MPB and TCS had a relatively small, but detectable impact on the metabolome. Multiple metabolites that were affected by chemical exposure belonged to the same biochemical pathways including phenol sulfonation and metabolism of pyruvate, lyso-plasmalogens, unsaturated fatty acids and serotonin. Changes in phenol sulfonation and pyruvate metabolism were most pronounced in rats exposed to DEP during the prepubertal period. Our metabolomics analysis demonstrates that human level exposure to personal care product ingredients has detectable effects on the rat metabolome. We highlight specific pathways such as sulfonation that warrant further study.

  4. Mechanism underlying the effect of long-term exposure to low dose of pesticides on DNA integrity.

    Science.gov (United States)

    Alleva, Renata; Manzella, Nicola; Gaetani, Simona; Bacchetti, Tiziana; Bracci, Massimo; Ciarapica, Veronica; Monaco, Federica; Borghi, Battista; Amati, Monica; Ferretti, Gianna; Tomasetti, Marco

    2018-04-01

    Pesticides, including herbicides, insecticides and fungicides, are widely used in intensive agriculture. Recently, the long-term effects of pesticide exposure were found to be associated with many diseases. In this study, we evaluated the long-term effect of low-level exposure to a mixture of pesticides on DNA damage response (DDR) in relation to individual detoxifying variability. A residential population chronically exposed to pesticides was enrolled, biological/environmental pesticide levels; paroxonase 1 (PON-1) activity and 192 Q/R polymorphism and DDR were evaluated at three different periods of pesticide exposure. OGG1-dependent DNA repair activity was decreased in relation to pesticide exposure. The increase of DNA lesions and pesticide levels in the intensive pesticide-spraying period was independent on PON-1 activity. Next, human bronchial epithelial and neuronal cells were used as a model for in vitro evaluation of the mechanistic effect of pesticides. Pesticides induced mitochondrial dysfunction leading to ROS formation. ROS from mitochondria induced DNA damage, which in turn induced OGG1-dependent DNA repair activity through 8-oxoguanine DNA glycosylase 1 (OGG1) expression and activation. Even though OGG1 was overexpressed, an inhibition of its activity, associated with DNA lesion accumulation, was found at prolonged pesticide-exposure. A post-translational regulation of OGG1 by pesticide may be postulated. Taken together, long-term exposure to low-levels of pesticides affects DDR resulting in accumulation of DNA lesions that eventually may lead to cancer or neurological disorders. © 2018 Wiley Periodicals, Inc.

  5. Low doses effects

    International Nuclear Information System (INIS)

    Tubiana, M.

    1997-01-01

    In this article is asked the question about a possible carcinogens effect of low dose irradiation. With epidemiological data, knowledge about the carcinogenesis, the professor Tubiana explains that in spite of experiments made on thousand or hundred of thousands animals it has not been possible to bring to the fore a carcinogens effect for low doses and then it is not reasonable to believe and let the population believe that low dose irradiation could lead to an increase of neoplasms and from this point of view any hardening of radiation protection standards could in fact, increase anguish about ionizing radiations. (N.C.)

  6. N-Acetyl Cysteine does not prevent liver toxicity from chronic low dose plus sub-acute high dose paracetamol exposure in young or old mice

    Science.gov (United States)

    Kane, Alice-Elizabeth; Huizer-Pajkos, Aniko; Mach, John; McKenzie, Catriona; Mitchell, Sarah-Jayne; de Cabo, Rafael; Jones, Brett; Cogger, Victoria; Le Couteur, David G; Hilmer, Sarah-Nicole

    2016-01-01

    Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute over-exposures. The risk of hepatotoxicity from non-acute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for non-acute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and sub-acute paracetamol over-exposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33g/kg food) or control diet for 6 weeks. Mice were then dosed orally 8 times over 3 days with additional paracetamol (250mg/kg) or saline, followed by either one or two doses of oral NAC (1200mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Sub-acute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from sub-acute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for sub-acute paracetamol toxicity. PMID:26821200

  7. Evaluation of the genotoxic effects of chronic low-dose ionizing radiation exposure on nuclear medicine workers

    Energy Technology Data Exchange (ETDEWEB)

    Sahin, Ali [Department of Nuclear Medicine, Faculty of Medicine, Medical School, Ataturk University, Erzurum (Turkey)], E-mail: alibabam2001@yahoo.com; Tatar, Abdulgani; Oztas, Sitki [Department of Genetics, Faculty of Medicine, Ataturk University, 25240 Erzurum (Turkey); Seven, Bedri; Varoglu, Erhan [Department of Nuclear Medicine, Faculty of Medicine, Medical School, Ataturk University, Erzurum (Turkey); Yesilyurt, Ahmet [Department of Genetics, Faculty of Medicine, Ataturk University, 25240 Erzurum (Turkey); Ayan, Arif Kursad [Department of Nuclear Medicine, Faculty of Medicine, Medical School, Ataturk University, Erzurum (Turkey)

    2009-07-15

    Introduction: Nuclear medicine workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation may have damaging effects on chromosomes. In the present study, we investigated the genotoxic effects of ionizing radiation on nuclear medicine workers. We used two different indicators of genotoxicity methods: sister chromatid exchange (SCE) and micronucleus (MN). Methods: The present research was carried out using 21 nuclear medicine workers (11 females and 10 males) during two periods: during normal working conditions and after a 1-month vacation. The radiation dose varied from 1.20 to 48.56 mSv, which accumulated during the occupational exposure time between two vacations. Peripheral blood samples were taken from each subject for two distinct lymphocyte cultures (SCE and MN) in each period. Results: In nearly all subjects, SCE values increased significantly during radiation exposure compared to the postvacation period (P<.05). Similarly, MN frequencies in most of the subjects increased significantly during radiation exposure compared to the postvacation period (P<.05). Conclusions: This study revealed that both SCE and MN frequencies in most of the subjects were significantly higher during exposure to ionizing radiation than after a 1-month vacation period. However, this genotoxic effect was reversible in most of the subjects.

  8. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

    NARCIS (Netherlands)

    Goodson, William H.; Lowe, Leroy; Carpenter, David O.; Gilbertson, Michael; Manaf Ali, Abdul; Lopez de Cerain Salsamendi, Adela; Lasfar, Ahmed; Carnero, Amancio; Azqueta, Amaya; Amedei, Amedeo; Charles, Amelia K.; Collins, Andrew R.; Ward, Andrew; Salzberg, Anna C.; Colacci, Annamaria; Olsen, Ann-Karin; Berg, Arthur; Barclay, Barry J.; Zhou, Binhua P.; Blanco-Aparicio, Carmen; Baglole, Carolyn J.; Dong, Chenfang; Mondello, Chiara; Hsu, Chia-Wen; Naus, Christian C.; Yedjou, Clement; Curran, Colleen S.; Laird, Dale W.; Koch, Daniel C.; Carlin, Danielle J.; Felsher, Dean W.; Roy, Debasish; Brown, Dustin G.; Ratovitski, Edward; Ryan, Elizabeth P.; Corsini, Emanuela; Rojas, Emilio; Moon, Eun-Yi; Laconi, Ezio; Marongiu, Fabio; Al-Mulla, Fahd; Chiaradonna, Ferdinando; Darroudi, Firouz; Martin, Francis L.; van Schooten, Frederik J.; Goldberg, Gary S.; Wagemaker, Gerard; Nangami, Gladys N.; Calaf, Gloria M.; Williams, Graeme; Wolf, Gregory T.; Koppen, Gudrun; Brunborg, Gunnar; Lyerly, H. Kim; Krishnan, Harini; Ab Hamid, Hasiah; Yasaei, Hemad; Sone, Hideko; Kondoh, Hiroshi; Salem, Hosni K.; Hsu, Hsue-Yin; Park, Hyun Ho; Koturbash, Igor; Miousse, Isabelle R.; Scovassi, A. Ivana; Klaunig, James E.; Vondráček, Jan; Raju, Jayadev; Roman, Jesse; Wise, John Pierce; Whitfield, Jonathan R.; Woodrick, Jordan; Christopher, Joseph A.; Ochieng, Josiah; Martinez-Leal, Juan Fernando; Weisz, Judith; Kravchenko, Julia; Sun, Jun; Prudhomme, Kalan R.; Narayanan, Kannan Badri; Cohen-Solal, Karine A.; Moorwood, Kim; Gonzalez, Laetitia; Soucek, Laura; Jian, Le; D'Abronzo, Leandro S.; Lin, Liang-Tzung; Li, Lin; Gulliver, Linda; McCawley, Lisa J.; Memeo, Lorenzo; Vermeulen, Louis; Leyns, Luc; Zhang, Luoping; Valverde, Mahara; Khatami, Mahin; Romano, Maria Fiammetta; Chapellier, Marion; Williams, Marc A.; Wade, Mark; Manjili, Masoud H.; Lleonart, Matilde E.; Xia, Menghang; Gonzalez, Michael J.; Karamouzis, Michalis V.; Kirsch-Volders, Micheline; Vaccari, Monica; Kuemmerle, Nancy B.; Singh, Neetu; Cruickshanks, Nichola; Kleinstreuer, Nicole; van Larebeke, Nik; Ahmed, Nuzhat; Ogunkua, Olugbemiga; Krishnakumar, P. K.; Vadgama, Pankaj; Marignani, Paola A.; Ghosh, Paramita M.; Ostrosky-Wegman, Patricia; Thompson, Patricia A.; Dent, Paul; Heneberg, Petr; Darbre, Philippa; Sing Leung, Po; Nangia-Makker, Pratima; Cheng, Qiang Shawn; Robey, R. Brooks; Al-Temaimi, Rabeah; Roy, Rabindra; Andrade-Vieira, Rafaela; Sinha, Ranjeet K.; Mehta, Rekha; Vento, Renza; Di Fiore, Riccardo; Ponce-Cusi, Richard; Dornetshuber-Fleiss, Rita; Nahta, Rita; Castellino, Robert C.; Palorini, Roberta; Abd Hamid, Roslida; Langie, Sabine A. S.; Eltom, Sakina E.; Brooks, Samira A.; Ryeom, Sandra; Wise, Sandra S.; Bay, Sarah N.; Harris, Shelley A.; Papagerakis, Silvana; Romano, Simona; Pavanello, Sofia; Eriksson, Staffan; Forte, Stefano; Casey, Stephanie C.; Luanpitpong, Sudjit; Lee, Tae-Jin; Otsuki, Takemi; Chen, Tao; Massfelder, Thierry; Sanderson, Thomas; Guarnieri, Tiziana; Hultman, Tove; Dormoy, Valérian; Odero-Marah, Valerie; Sabbisetti, Venkata; Maguer-Satta, Veronique; Rathmell, W. Kimryn; Engström, Wilhelm; Decker, William K.; Bisson, William H.; Rojanasakul, Yon; Luqmani, Yunus; Chen, Zhenbang; Hu, Zhiwei

    2015-01-01

    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is

  9. Evaluation of the genotoxic effects of chronic low-dose ionizing radiation exposure on nuclear medicine workers

    International Nuclear Information System (INIS)

    Sahin, Ali; Tatar, Abdulgani; Oztas, Sitki; Seven, Bedri; Varoglu, Erhan; Yesilyurt, Ahmet; Ayan, Arif Kursad

    2009-01-01

    Introduction: Nuclear medicine workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation may have damaging effects on chromosomes. In the present study, we investigated the genotoxic effects of ionizing radiation on nuclear medicine workers. We used two different indicators of genotoxicity methods: sister chromatid exchange (SCE) and micronucleus (MN). Methods: The present research was carried out using 21 nuclear medicine workers (11 females and 10 males) during two periods: during normal working conditions and after a 1-month vacation. The radiation dose varied from 1.20 to 48.56 mSv, which accumulated during the occupational exposure time between two vacations. Peripheral blood samples were taken from each subject for two distinct lymphocyte cultures (SCE and MN) in each period. Results: In nearly all subjects, SCE values increased significantly during radiation exposure compared to the postvacation period (P<.05). Similarly, MN frequencies in most of the subjects increased significantly during radiation exposure compared to the postvacation period (P<.05). Conclusions: This study revealed that both SCE and MN frequencies in most of the subjects were significantly higher during exposure to ionizing radiation than after a 1-month vacation period. However, this genotoxic effect was reversible in most of the subjects.

  10. Occupational exposure to low doses of ionizing radiation and cataract development: a systematic literature review and perspectives on future studies

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, Gael P. [University Medical Center of the Johannes Gutenberg University Mainz, Institute for Medical Biostatistics, Epidemiology and Informatics (IMBEI), Mainz (Germany); Registre Morphologique des Tumeurs, Laboratoire National de Sante, Luxembourg (Luxembourg); Scheidemann-Wesp, Ulrike; Wicke, Henryk; Blettner, Maria [University Medical Center of the Johannes Gutenberg University Mainz, Institute for Medical Biostatistics, Epidemiology and Informatics (IMBEI), Mainz (Germany); Samkange-Zeeb, Florence [University Medical Center of the Johannes Gutenberg University Mainz, Institute for Medical Biostatistics, Epidemiology and Informatics (IMBEI), Mainz (Germany); Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH, Department of Prevention and Evaluation, Bremen (Germany); Neriishi, Kazuo [Radiation Effects Research Foundation, Hiroshima (Japan)

    2013-08-15

    Ionizing radiation is a well-known but little understood risk factor for lens opacities. Until recently, cataract development was considered to be a deterministic effect occurring at lens doses exceeding a threshold of 5-8 Gy. Substantial uncertainty about the level and the existence of a threshold subsists. The International Commission on Radiation Protection recently revised it to 0.5 Gy. Based on a systematic literature review of epidemiological studies on exposure to low levels of ionizing radiation and the occurrence of lens opacities, a list of criteria for new epidemiological studies was compiled, and a list of potential study populations was reviewed. Among 24 publications finally identified, six report analyses of acute exposures in atomic bomb survivors and Chernobyl liquidators, and the others report analyses of protracted exposures in occupationally, medically or accidentally exposed populations. Three studies investigated a dose threshold: in atomic bomb survivors, the best estimates were 1 Sv (95 % CI <0-0.8 Sv) regarding lensectomies; in survivors exposed as children, 0.6 Sv (90 % CI <0.0-1.2 Sv) for cortical cataract prevalence and 0.7 Sv (90 % CI 0.0-2.8 Sv) for posterior subcapsular cataract; and in Chernobyl liquidators, 0.34 Sv (95 % CI 0.19-0.68 Sv) for stage 1 cataract. Current studies are heterogeneous and inconclusive regarding the dose-response relationship. Protracted exposures and high lens doses occur in several occupational groups, for instance, in physicians performing fluoroscopy-guided interventional procedures, and in accidentally exposed populations. New studies with a good retrospective exposure assessment are feasible and should be initiated. (orig.)

  11. Analgesia induced by repeated exposure to low dose X-rays in mice, and involvement of the accessory olfactory system in modulation of the radiation effects

    International Nuclear Information System (INIS)

    Miyachi, Yukihisa; Yamada, Takeshi

    1997-01-01

    The effects of low-dose X-rays on mouse nociceptive behavior were examined using a formalin injected test which rated the amount of time the animals spent licking the injected hind-paw. Male ICR White Swiss mice showed a marked suppression of licking behavior after repeated low-dose X-irradiation (5 cGy/day, 6 consecutive days). The most profound effect was observed on the day 30 after irradiation. The decline of licking behavior, however, was not observed at all following olfactory bulbectomy or vomeronasal tract cut. The analgesic effects could be observed in writhing animals administered acetic-acid intraperitoneally. Moreover, analgesia was totally blocked by the administration of N-nitro-L-arginine, a nitric oxide synthase inhibitor, to accessory olfactory bulbs prior to the exposure. The present results indicate that the olfactory system plays an important role in modulation of radiation-induced analgesia, and a possible involvement of nitric oxide in the formation of recognition memory subjected to repeated X-rays. Relatively higher doses (5 cGy x 9 days, 5 cGy x 12 days), however, did not induce such effects, namely, the decline of nociceptive response was limited to the animals irradiated with the smaller dose. (author)

  12. Comparative response of dogs and monkeys to sublethal acute and continuous low dose-rate gamma-ray exposure

    International Nuclear Information System (INIS)

    Spalding, J.F.; Holland, L.M.; Johnson, O.S.; LaBauve, P.M.; London, J.E.; Prine, J.R.; Vigil, E.A.

    1977-02-01

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (injury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with 35 R/day until death to determine the amount of radiation-induced injury remaining in conditioned animals as a reduction in mean survival time. Dogs (50 percent) and monkeys (8 percent) died from injury incurred during the conditioning exposures. Thus, the comparative response of dogs and monkeys to dose protraction by acute dose fractionation was similar to what might be expected from a single acute dose. Mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approximately 1400 h). Thus, hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35 R/day gamma-ray challenge exposure were greater than for their control counterparts. Thus, the long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than four times the acute LD 50 - 30 in dogs and approximately two times that of monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 R/day

  13. Metabolomics reveals dose effects of low-dose chronic exposure to uranium in rats: identification of candidate biomarkers in urine samples.

    Science.gov (United States)

    Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Éric; Dublineau, Isabelle; Aigueperse, Jocelyne; Bohand, Sandra; Martin, Jean-Charles; Souidi, Maâmar

    2016-01-01

    Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake. In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L -1 ; duration: 9 months, n = 10). In the present study, our aim was to investigate the dose-effect pattern and identify additional potential biomarkers in urine samples. Compared to our previous protocol, we doubled the number of rats per group (n = 20), added additional sampling time points (3 and 6 months) and included several lower doses of natural uranium (doses used: 40, 1.5, 0.15 and 0.015 mg L -1 ). LC-MS metabolomics was performed on urine samples and statistical analyses were made with SIMCA-P+ and R packages. The data confirmed our previous results and showed that discrimination was both dose and time related. Uranium exposure was revealed in rats contaminated for 9 months at a dose as low as 0.15 mg L -1 . Eleven features, including the confidently identified N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide and 4-hydroxyphenylacetylglycine, discriminated control from contaminated rats with a specificity and a sensitivity ranging from 83 to 96 %, when combined into a composite score. These findings show promise for the elucidation of underlying radiotoxicologic mechanisms and the design of a diagnostic test to assess exposure in urine, in a dose range experimentally estimated to be above a threshold between 0.015 and 0.15 mg L -1 .

  14. Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

    International Nuclear Information System (INIS)

    Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

    2016-01-01

    The presence of 137 Cesium ( 137 Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137 Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l −1 ) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137 Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation.

  15. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Liza S; Osipov, Andrian N; Zhuravleva, Veronika F; Pankratova, Galina V; Porokhovnik, Lev N; Veiko, Natalia N

    2015-09-01

    The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism's cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1×Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab DNA and TM values may provide the information about the human organism's cell resistivity to chronic exposure to the low-dose IR and about the development of the adaptive response in the organism that is aimed, firstly, at the effective cfDNA elimination from the blood circulation, and, secondly - at survival of the cells, including the cells with the damaged DNA. Copyright © 2015. Published by Elsevier B.V.

  16. Long term exposure to low dose neurotoxic pesticides affects hatching, viability and cholinesterase activity of Artemia sp.

    Science.gov (United States)

    Gambardella, Chiara; Nichino, Daniela; Iacometti, Camillo; Ferrando, Sara; Falugi, Carla; Faimali, Marco

    2018-03-01

    The brine shrimp Artemia was used as a model organism to test toxicity of several neuroactive pesticides (chlorpyrifos (CLP), chlorpyrifos oxon (CLP ox), diazinon (DZN), carbaryl (CBR)) following exposure to far below than lethal doses. Cysts were exposed to the pesticides in order to test a scenario similar to actual coastal environment contamination, by analyzing different responses. Cysts were rehydrated in water containing the pesticides at concentrations ranging from 10 -11 to 10 -5  M, for 72, 96 and 192 h, respectively. For these exposure times, morpho-functional and biochemical parameters, such as hatching speed and viability were investigated in the larvae together with cholinesterase (ChE) activity quantification and histochemical localization. Finally, ChE inhibition was also compared with conventional selective ChE inhibitors. Results showed that CLP ox and CBR caused a significant dose-dependent decrease in hatching speed, followed by high percentages of larval death, while CLP and DZN were responsible for irregular hatching patterns. In addition, the pesticides mostly caused larval death some days post-hatching, whereas this effect was negligible for the specific ChE inhibitors, suggesting that part of pesticide toxicity may be due to molecules other than the primary target. ChE activity was observed in the protocerebrum lobes, linked to the development of pair eyes. Such activity was inhibited in larvae exposed to all pesticides. When compared to conventional selective inhibitors of ChE activities, this inhibition demonstrated that the selected pesticides mainly affect acetylcholinesterase and, to a lesser extent, pseudocholinesterases. In conclusion, the brine shrimp is a good model to test the environmental toxicity of long term exposure to cholinergic pesticides, since changes in hatching speed, viability and ChE activity were observed. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. DNA Damage Following Pulmonary Exposure by Instillation to Low Doses of Carbon Black (Printex 90) Nanoparticles in Mice

    DEFF Research Database (Denmark)

    Kyjovska, Zdenka O.; Jacobsen, Nicklas R.; Saber, Anne T.

    2015-01-01

    of 0.67, 2, 6, and 162 mu g Printex 90 NPCB and vehicle. Cellular composition and protein concentration was evaluated in BAL fluid as markers of inflammatory response and cell damage. DNA strand breaks in BAL cells, lung, and liver tissue were assessed using the alkaline comet assay. The pulmonary...... the comet assay. We interpret the increased DNA strand breaks occurring following these low exposure doses of NPCB as DNA damage caused by primary genotoxicity in the absence of substantial inflammation, cell damage, and acute phase response. Environ. Mol. Mutagen. 56:41-49, 2015. (c) 2014 The Authors...

  18. Early exposure to a low dose of bisphenol A affects socio-sexual behavior of juvenile female rats.

    Science.gov (United States)

    Porrini, Stefania; Belloni, Virginia; Della Seta, Daniele; Farabollini, Francesca; Giannelli, Giuletta; Dessì-Fulgheri, Francesco

    2005-04-15

    Play behavior is affected by alteration of the hormonal environment during development. In fact, congenital adrenal hyperplasia or early administration of diethylstilbestrol are able to modify female play behavior in mammals. In this research, play behavior of female rats was used to explore the effects of perinatal exposure to low, environmentally relevant dose of bisphenol A (BPA), a xenoestrogen widely diffused in the environment. We used 18 females born to mothers exposed to 40 microg/kg/day BPA during pregnancy and lactation, and 18 control females. The subjects were observed in a heterosexual social situation from 35 to 55 days of age. Six main behaviors were identified by principal component analysis (PCA): exploration, defensive behavior to males, play behavior with males, play behavior with females, low-intensity mating behavior, social grooming. Early administration of BPA was responsible for a significant increase of exploration (including social investigation) (pbehavior, but is able however to defeminize some aspects of female behavior. This result is compatible with the estrogenic properties of BPA, and suggests caution in the use of a chemical that, in the range of human exposure, is able to influence the development of the brain during a critical period, resulting in long-term effects on behavior.

  19. Effects of chronic exposure of seeds and seeds and seedlings of Arabidopsis Thaliana by low doses of γ-radiation on plant growth and development

    International Nuclear Information System (INIS)

    Litvinov, S.V.

    2013-01-01

    Article presents the results of research on the effect of chronic γ-irradiation in small doses on A. Thaliana seedlings and seeds growth and development. Exposure rate for the seeds was 0,45 mGy/h (total absorbed dose 30 cSv) and 0,18 mGy/h for seedlings (total absorbed dose 3 cSv). Statistically significant differences in the germination capacity, in the time of primary leaf rosette formation, in the hypocotyl length were revealed between irradiated and control seedlings. Plants from irradiated seeds differed by the higher growth rate of stem, they flowered and fruited earlier, but they also characterized on average shorter vegetative cycle in comparison with control plants. In our experiments it is shown significant impact of chronic low doses of γ-irradiation of seeds and seedlings on the ontogeny in A. Thaliana and on the parameters that reflect the growth and development of the irradiated plants

  20. Low dose ionizing radiation exposure and cardiovascular disease mortality: cohort study based on Canadian national dose registry of radiation workers

    International Nuclear Information System (INIS)

    Zielinski, J. M.; Band, P. R.; Ashmore, P. J.; Jiang, H.; Shilnikova, N. S.; Tait, V. K.; Krewski, D.

    2009-01-01

    The purpose of our study was to assess the risk of cardiovascular disease (CVD) mortality in a Canadian cohort of 337 397 individuals (169 256 men and 168 141 women) occupationally exposed to ionizing radiation and included in the National Dose Registry (NDR) of Canada. Material and Methods: Exposure to high doses of ionizing radiation, such as those received during radiotherapy, leads to increased risk of cardiovascular diseases. The emerging evidence of excess risk of CVDs after exposure to doses well below those previously considered as safe warrants epidemiological studies of populations exposed to low levels of ionizing radiation. In the present study, the cohort consisted of employees at nuclear power stations (nuclear workers) as well as medical, dental and industrial workers. The mean whole body radiation dose was 8.6 mSv for men and 1.2 mSv for women. Results: During the study period (1951 - 1995), as many as 3 533 deaths from cardiovascular diseases have been identified (3 018 among men and 515 among women). In the cohort, CVD mortality was significantly lower than in the general population of Canada. The cohort showed a significant dose response both among men and women. Risk estimates of CVD mortality in the NDR cohort, when expressed as excess relative risk per unit dose, were higher than those in most other occupational cohorts and higher than in the studies of Japanese atomic bomb survivors. Conclusions: The study has demonstrated a strong positive association between radiation dose and the risk of CVD mortality. Caution needs to be exercised when interpreting these results, due to the potential bias introduced by dosimetry uncertainties, the possible record linkage errors, and especially by the lack of adjustment for non-radiation risk factors. (authors)

  1. Effect of extended exposure to low-dose radiation on autoimmune diseases of immunologically suppressed MRL/MpTn-gld/gld mice

    International Nuclear Information System (INIS)

    Ootsuyama, Akira; Okazaki, Ryuji; Norimura, Toshiyuki

    2003-01-01

    The purpose of this paper is to analyze the relationship between alterations of splenic T-cell subpopulations and the amelioration of autoimmune diseases of MRL/MpTn-gld/gld mice (MRL/gld mice) after extended exposure to low-dose radiation. After the onset of disease, 4-month-old MRL/gld mice were exposed to doses of 0.05, 0.2, and 0.5 Gy/day for 4 weeks (5 days/week), for total doses of 1, 4, and 10 Gy, respectively. The MRL/gld mice that were irradiated with 0.2 and 0.5 Gy/day showed an obvious decrease in the proportion of splenic CD4 - CD8 - T cells and remission of their autoimmune diseases. After the last irradiation, apoptotic cells were found in the white pulp of the spleen of the MRL/gld mice irradiated with 0.2 Gy/day, but not in the MRL/MpJ-+/+ mice (MRL/wild mice), which experienced a similar treatment. Before the onset of disease, 3-month-old MRL/gld mice subjected to 0.2 Gy/day showed a decrease in the proportion of splenic CD4 - CD8 - T cells and less remission of their autoimmune diseases than the 4-month-old mice. These results suggest that the accumulated CD4 - CD8 - T cells are more sensitive to radiation than other T cell subpopulations, and that decreasing CD4 - CD8 - T cells with extended exposure to low-dose radiation leads to the amelioration of autoimmune disease. (author)

  2. Effects of prenatal exposure to low-dose β radiation from tritiated water on the neutrobehavior of mice

    International Nuclear Information System (INIS)

    Wang Bing; Zhou Xiangyan.

    1995-01-01

    Pregnant adult C57BL/6J mice, randomly assigned to 1 of 4 groups, 3 of them were irradiated with β-rays from tritiated water (HTO) by a single intraperitoneal injection on the 12.5th day of gestation. Their offspring received cumulative doses of 0, 5, 10 or 30 cGy in utero. Male pups were trained and examined using a set of behavioral tests that included avoidance acquisition and avoidance maintenance, open field test, hole-board dipping, a water maze, and a food labyrinth. Results were found for most parameters in the 10 and 30 cGy groups that differed significantly from results for the controls, indicating that the behavioral teratogenic effect of prenatal exposure to chronic β-ray radiation from HTO may be greater than the same dose of acute X- or γ-irradiation and that 10 cGy may be the lowest detectable dose level at which behavioral changes is detectable under the conditions used in this experiment. (author) 56 refs

  3. Effects of prenatal exposure to low-dose {beta} radiation from tritiated water on the neutrobehavior of mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang Bing [Tokyo Univ. (Japan). Faculty of Science; Zhou Xiangyan

    1995-06-01

    Pregnant adult C57BL/6J mice, randomly assigned to 1 of 4 groups, 3 of them were irradiated with {beta}-rays from tritiated water (HTO) by a single intraperitoneal injection on the 12.5th day of gestation. Their offspring received cumulative doses of 0, 5, 10 or 30 cGy in utero. Male pups were trained and examined using a set of behavioral tests that included avoidance acquisition and avoidance maintenance, open field test, hole-board dipping, a water maze, and a food labyrinth. Results were found for most parameters in the 10 and 30 cGy groups that differed significantly from results for the controls, indicating that the behavioral teratogenic effect of prenatal exposure to chronic {beta}-ray radiation from HTO may be greater than the same dose of acute X- or {gamma}-irradiation and that 10 cGy may be the lowest detectable dose level at which behavioral changes is detectable under the conditions used in this experiment. (author) 56 refs.

  4. Nanoscale-Barrier Formation Induced by Low-Dose Electron-Beam Exposure in Ultrathin MoS2 Transistors.

    Science.gov (United States)

    Matsunaga, Masahiro; Higuchi, Ayaka; He, Guanchen; Yamada, Tetsushi; Krüger, Peter; Ochiai, Yuichi; Gong, Yongji; Vajtai, Robert; Ajayan, Pulickel M; Bird, Jonathan P; Aoki, Nobuyuki

    2016-10-05

    Utilizing an innovative combination of scanning-probe and spectroscopic techniques, supported by first-principles calculations, we demonstrate how electron-beam exposure of field-effect transistors, implemented from ultrathin molybdenum disulfide (MoS 2 ), may cause nanoscale structural modifications that in turn significantly modify the electrical operation of these devices. Quite surprisingly, these modifications are induced by even the relatively low electron doses used in conventional electron-beam lithography, which are found to induce compressive strain in the atomically thin MoS 2 . Likely arising from sulfur-vacancy formation in the exposed regions, the strain gives rise to a local widening of the MoS 2 bandgap, an idea that is supported both by our experiment and by the results of first-principles calculations. A nanoscale potential barrier develops at the boundary between exposed and unexposed regions and may cause extrinsic variations in the resulting electrical characteristics exhibited by the transistor. The widespread use of electron-beam lithography in nanofabrication implies that the presence of such strain must be carefully considered when seeking to harness the potential of atomically thin transistors. At the same time, this work also promises the possibility of exploiting the strain as a means to achieve "bandstructure engineering" in such devices.

  5. Identification of Differential Gene Expression Patterns after Acute Exposure to High and Low Doses of Low-LET Ionizing Radiation in a Reconstituted Human Skin Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, Susan C.; Markillie, Lye Meng; Hays, Spencer; Taylor, Ronald C.; Stenoien, David L.

    2016-11-01

    Our goal here was to identify dose and temporal dependent radiation responses in a complex tissue, reconstituted human skin. Direct sequencing of RNA (RNA-seq) was used to quantify altered transcripts following exposure to 0.1, 2 and 10 Gy of ionizing radiation at 3 and 8 hours. These doses include a low dose in the range of some medical diagnostic procedures (0.1 Gy), a dose typically received during radiotherapy (2.0 Gy) and a lethal dose (10 Gy). These doses could be received after an intentional or accidental radiation exposure and biomarkers are needed to rapidly and accurately triage exposed individuals. A total of 1701 genes were deemed to be significantly affected by high dose radiation exposure with the majority of genes affected at 10 Gy. A group of 29 genes including GDF15, BBC3, PPM1D, FDXR, GADD45A, MDM2, CDKN1A, TP53INP1, CYCSP27, SESN1, SESN2, PCNA, and AEN were similarly altered at both 2 and 10 Gy, but not 0.1 Gy, at multiple time points. A much larger group of up regulated genes, including those involved in inflammatory responses, was significantly altered only after a 10 Gy exposure. At high doses, down regulated genes were associated with cell cycle regulation and exhibited an apparent linear response between 2 and 10 Gy. While only a handful of genes were significantly affected by 0.1 Gy exposure using stringent statistical filters, groups of related genes regulating cell cycle progression and inflammatory responses consistently exhibited opposite trends in their regulation compared to the high dose exposures. Differential regulation of PLK1 signaling at low and high doses was confirmed using qRT-PCR. These results indicate that some alterations in gene expression are qualitatively different at low and high doses of radiation in this model system.

  6. Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure.

    Directory of Open Access Journals (Sweden)

    Esther L Calderon-Gierszal

    Full Text Available Studies using rodent and adult human prostate stem-progenitor cell models suggest that developmental exposure to the endocrine disruptor Bisphenol-A (BPA can predispose to prostate carcinogenesis with aging. Unknown at present is whether the embryonic human prostate is equally susceptible to BPA during its natural developmental window. To address this unmet need, we herein report the construction of a pioneer in vitro human prostate developmental model to study the effects of BPA. The directed differentiation of human embryonic stem cells (hESC into prostatic organoids in a spatial system was accomplished with precise temporal control of growth factors and steroids. Activin-induced definitive endoderm was driven to prostate specification by combined exposure to WNT10B and FGF10. Matrigel culture for 20-30 days in medium containing R-Spondin-1, Noggin, EGF, retinoic acid and testosterone was sufficient for mature prostate organoid development. Immunofluorescence and gene expression analysis confirmed that organoids exhibited cytodifferentiation and functional properties of the human prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing and 10 nM BPA reducing the number of branched structures formed. While differentiation of branched structures to mature organoids seemed largely unaffected by BPA exposure, the stem-like cell population increased, appearing as focal stem cell nests that have not properly entered lineage commitment rather than the rare isolated stem cells found in normally differentiated structures. These findings provide the first direct evidence that low-dose BPA exposure targets hESC and perturbs morphogenesis as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by in utero BPA exposures.

  7. Dietary exposure to a low dose of pesticides alone or as a mixture: the biological metabolic fingerprint and impact on hematopoiesis.

    Science.gov (United States)

    Demur, C; Métais, B; Canlet, C; Tremblay-Franco, M; Gautier, R; Blas-Y-Estrada, F; Sommer, C; Gamet-Payrastre, L

    2013-06-07

    Consumers are exposed to a mixture of pesticides through their food intake. These compounds are considered risk factors for human health, and the impact of dietary exposure to low doses of pesticide mixtures remains poorly understood. For this study we developed a mouse model to mimic consumer exposure in order to compare the effect of pesticides both alone or combined at doses corresponding to their Acceptable Daily Intake value. Female mice were exposed to pesticides throughout gestation and lactation. After weaning pups were fed the same pesticide-enriched diet their mothers had received for an additional 11 weeks. A metabonomic approach using (1)H NMR-based analysis of plasma showed that exposure to each pesticide produced a specific metabolic fingerprint in adult offspring. Discriminant metabolites between groups were glucose or lactate, choline, glycerophosphocholine and phosphocholine. Interestingly, metabolite differences were observed as early as weaned animals that had not yet been directly exposed themselves. Studies of the hematopoietic system revealed that dietary exposure to one particular pesticide, endosulfan, produced a significant decrease in red blood cell and hemoglobin levels, consistent with hemolytic anemia. Moreover, cell signaling profiles of bone marrow progenitors were also clearly affected. Expression of cell signaling proteins such as P35, CDC27, FAK, P38 MAP kinase, calcineurin and caspase as well as proteins involved in the stability or structure of the cytoskeleton (vinculin, MAP2) was changed upon dietary exposure to pesticides. Finally, we found that dietary exposure to a mixture of pesticides had effects that differed and were often lesser or equal to that of the most efficient pesticide (endosulfan), suggesting that the effect of pesticide mixtures cannot always be predicted from the combined effects of their constituent compounds. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Biological dosimetry - a Bayesian approach in the presentation of the uncertainty of the estimated dose in cases of exposure to low dose radiation

    International Nuclear Information System (INIS)

    Di Giorgio, Marina; Zaretzky, A.

    2010-01-01

    Biodosimetry laboratory experience has shown that there are limitations in the existing statistical methodology. Statistical difficulties generally occur due to the low number of aberrations leading to large uncertainties for dose estimation. Some problems derived from limitations of the classical statistical methodology, which requires that chromosome aberration yields be considered as something fixed and consequently provides a deterministic dose estimation and associated confidence limits. On the other hand, recipients of biological dosimetry reports, including medical doctors, regulators and the patients themselves may have a limited comprehension of statistics and of informed reports. Thus, the objective of the present paper is to use a Bayesian approach to present the uncertainty on the estimated dose to which a person could be exposed, in the case of low dose (occupational doses) radiation exposure. Such methodology will allow the biodosimetrists to adopt a probabilistic approach for the cytogenetic data analysis. At present, classical statistics allows to produce a confidence interval to report such dose, with a lower limit that could not detach from zero. In this situation it becomes difficult to make decisions as they could impact on the labor activities of the worker if an exposure exceeding the occupational dose limits is inferred. The proposed Bayesian approach is applied to occupational exposure scenario to contribute to take the appropriate radiation protection measures. (authors) [es

  9. The Fukushima nuclear accident and the pale grass blue butterfly: evaluating biological effects of long-term low-dose exposures.

    Science.gov (United States)

    Hiyama, Atsuki; Nohara, Chiyo; Taira, Wataru; Kinjo, Seira; Iwata, Masaki; Otaki, Joji M

    2013-08-12

    On August 9th 2012, we published an original research article in Scientific Reports, concluding that artificial radionuclides released from the Fukushima Dai-ichi Nuclear Power Plant exerted genetically and physiologically adverse effects on the pale grass blue butterfly Zizeeria maha in the Fukushima area. Immediately following publication, many questions and comments were generated from all over the world. Here, we have clarified points made in the original paper and answered questions posed by the readers. The following points were clarified. (1) There are many advantages to using the pale grass blue butterfly as an indicator species. (2) The forewings of the individuals collected in Fukushima were significantly smaller than in the northern and southern localities. (3) We observed growth retardation in the butterflies from the Fukushima area. (4) The aberrant colour patterns in the butterflies obtained in the Fukushima area were different from the colour patterns induced by temperature and sibling crosses but similar to those induced by external and internal exposures to the artificial radionuclides and by a chemical mutagen, suggesting that genetic mutations caused the aberrations. (5) This species of butterfly has been plentiful in Fukushima area for at least half a century. We here present specimens collected from Fukushima Prefecture before the accident. (6) Mutation accumulation was detected by the increase in the abnormality rates from May 2011 to September 2011. (7) The abnormal traits were heritable. (8) Our sampling localities were not affected by the tsunami. (9) We used a high enough number of samples to obtain statistically significant results. (10) The standard rearing method was followed, producing normal adults in the control groups. (11) The exposure experiments successfully reproduced the results of the field work. This species of butterfly is vulnerable to long-term low-dose internal and external exposures; however, insect cells are known to be

  10. SU-F-I-31: Reproducibility of An Automatic Exposure Control Technique in the Low-Dose CT Scan of Cardiac PET/CT Exams

    Energy Technology Data Exchange (ETDEWEB)

    Park, M; Rosica, D; Agarwal, V; Di Carli, M; Dorbala, S [Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (United States)

    2016-06-15

    Purpose: Two separate low-dose CT scans are usually performed for attenuation correction of rest and stress N-13 ammonia PET/CT myocardial perfusion imaging (PET/CT). We utilize an automatic exposure control (AEC) technique to reduce CT radiation dose while maintaining perfusion image quality. Our goal is to assess the reproducibility of displayed CT dose index (CTDI) on same-day repeat CT scans (CT1 and CT2). Methods: Retrospectively, we reviewed CT images of PET/CT studies performed on the same day. Low-dose CT utilized AEC technique based on tube current modulation called Smart-mA. The scan parameters were 64 × 0.625mm collimation, 5mm slice thickness, 0.984 pitch, 1-sec rotation time, 120 kVp, and noise index 50 with a range of 10–200 mA. The scan length matched with PET field of view (FOV) with the heart near the middle of axial FOV. We identified the reference slice number (RS) for an anatomical landmark (carina) and used it to estimate axial shift between two CTs. For patient size, we measured an effective diameter on the reference slice. The effect of patient positioning to CTDI was evaluated using the table height. We calculated the absolute percent difference of the CTDI (%diff) for estimation of the reproducibility. Results: The study included 168 adults with an average body-mass index of 31.72 ± 9.10 (kg/m{sup 2}) and effective diameter was 32.72 ± 4.60 cm. The average CTDI was 1.95 ± 1.40 mGy for CT1 and 1.97 ± 1.42mGy for CT2. The mean %diff was 7.8 ± 6.8%. Linear regression analysis showed a significant correlation between the table height and %diff CTDI. (r=0.82, p<0.001) Conclusion: We have shown for the first time in human subjects, using two same-day CT images, that the AEC technique in low-dose CT is reproducible within 10% and significantly depends on the patient centering.

  11. Statistical and low dose response

    International Nuclear Information System (INIS)

    Thorson, M.R.; Endres, G.W.R.

    1981-01-01

    The low dose response and the lower limit of detection of the Hanford dosimeter depend upon may factors, including the energy of the radiation, whether the exposure is to be a single radiation or mixed fields, annealing cycles, environmental factors, and how well various batches of TLD materials are matched in the system. A careful statistical study and sensitivity analysis were performed to determine how these factors influence the response of the dosimeter system. Estimates have been included in this study of the standard deviation of calculated dose for various mixed field exposures from 0 to 1000 mrem

  12. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Haytham [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Galal, Omima [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Abdelrahim, Eman [Department of Medical Histology, Qena Faculty of Medicine, South Valley University (Egypt); Ono, Yusuke [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Mostafa, Emtethal [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Li, Tao-Sheng, E-mail: litaoshe@nagasaki-u.ac.jp [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2014-09-26

    Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.

  13. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    International Nuclear Information System (INIS)

    Ali, Haytham; Galal, Omima; Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan; Abdelrahim, Eman; Ono, Yusuke; Mostafa, Emtethal; Li, Tao-Sheng

    2014-01-01

    Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit + stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit + stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit + stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms

  14. Low dose epidemiologic studies

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    In this chapter the BEIR committee has reviewed low-dose irradiation studies since the BEIR III report. They have considered the carcinogenic effectiveness of low-LET in populations exposed to radiation from a number of different sources: diagnostic radiography; fallout from nuclear weapons testing; nuclear installations; radiation in the workplace and high levels of natural background radiation

  15. Late radiation effects of low doses from occupational exposure. Antibodies to cytomegalovirus, Epstein-Barr virus and human T cell lymphotropic virus type 1 in radiological technologists

    Energy Technology Data Exchange (ETDEWEB)

    Kumagai, Etsuko; Tanoue, Shozo (Kumamoto Univ. (Japan). Coll. of Medical Science); Sawada, Shozo

    1989-05-01

    To elucidate the effects of long-term exposure to low dose irradiation, serostatus of antibodies to cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human T cell lymphotropic virus type 1 (HTLV-1) was determined in 99 radiological technologists and 96 healthy volunteers. Abnormal seropositivity rate for CMV was significantly higher in technologists working for 15 years or more than in those working for less than 15 years. For the same age group, however, there was no significant difference between technologists and controls. Seropositivity rates for EBV-viral capsid antigen (VSA)/IgG and early antigen (EA)/IgG were significantly higher in technologists working for 15 years or more than in the age-matched control group. In the group of technologists exposed to 0.3 Sv or more, seropositivity rates of these antibodies were significantly higher than in those exposed to less than 0.3 Sv. However, there was no correlation between exposure doses and both EBV-associated nuclear antigen antibody and HTLV-1 antibody. Few technologists seronegative for CMV antibody had seropositive antibodies of EBV-VCA/IgG and EA/IgG. For technologists seropositive for CMV antibody, 31% and 54% were seropositive for EBV-VCA/IgG and EA/IgG antibodies, respectively. (Namekawa, K).

  16. T cell potentiation in normal and autoimmune-prone mice after extended exposure to low doses of ionizing radiation and/or caloric restriction

    Energy Technology Data Exchange (ETDEWEB)

    James, S.J.; Makinodan, T.

    1988-01-01

    In order to better understand the apparent physiologic up-regulation in response to low levels of potentially lethal insults, murine T lymphocytes were analysed for functional and phenotypic alterations after exposure to 0.005 Gy/day, 0.01 Gy/day and 0.04 Gy/day in groups of ad-libitum-fed and calorie-restricted mice. Studies were conducted in two strains of mice: long-lived and immunologically normal C57B1/6 +/+ and congenic short-lived immunologically depressed C57B1/6 1pr/1pr. Whole-body exposure to 0.01 Gy/day and 0.04 Gy/day for an extended period of 20 days was associated with an increase in splenic proliferative response and shifts in proportions of T cell subpopulations in the thymus and spleen of both strains. Caloric restriction independently altered functional activity and T cell subpopulations in the same direction as low dose rates of ionizing radiation. Although dose-response augmentation in proliferative activity was similar in the strains, observed alterations in thymic and splenic T cell subpopulations were clearly different, suggesting different mechanisms were responsible for immune enhancement in each strain.

  17. Effects of low doses

    International Nuclear Information System (INIS)

    Le Guen, B.

    2001-01-01

    Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

  18. Lack of adverse health effects following 30-weeks of dietary exposure to acrylamide at low doses in male F344 rats

    Directory of Open Access Journals (Sweden)

    Jayadev Raju

    Full Text Available Understanding the health hazards following exposure to food-borne acrylamide, especially at low levels typified by human diets, is an ongoing food safety issue. We recently published results from a study that aimed to understand the effects of acrylamide short-term exposure at doses known to cause tumors in rodents, demonstrating that a number of key toxicological end points were altered by acrylamide exposure. Additionally, we reported that at much lower doses for 30 weeks of exposure, dietary acrylamide was ‘not a complete carcinogen’ to the colon in an organ-specific rodent carcinogenesis study but acted as a co-carcinogen along with azoxymethane (AOM, a colon-specific carcinogen. Here, we present toxicological data from a sub-set of this long-term exposure study from animals that received saline (instead of AOM. Briefly, male F344 rats were randomized to receive acrylamide at 0.5, 1.0 and 2.0 mg/kg diet (∼0.02, 0.04, and 0.09 mg/kg BW/day, respectively or no acrylamide (control, for 30 weeks; all rats were then euthanized and their tissues harvested and processed for toxicological evaluation. We report that at the doses tested, acrylamide did not cause any changes in general well-being, body weight or food intake. Similarly, acrylamide did not cause any biologically relevant change in parameters associated with immunophenotyping, serum biochemistry or hematology. Histopathology assessment of tissues showed no changes except in the testis, where non-specific mild lesions were observed in all the groups, inclusive of the controls. No neuropathological effects of acrylamide were observed in the brain and nerve tissues. Together, these results suggest that acrylamide administered to rats through the diet at low doses for 30 weeks did not cause any toxicologically relevant changes. Given that the doses of acrylamide in the current study are low and are comparable to human dietary exposure, this null-effect study provides data that

  19. Health effect of low dose/low dose rate radiation

    International Nuclear Information System (INIS)

    Kodama, Seiji

    2012-01-01

    The clarified and non-clarified scientific knowledge is discussed to consider the cause of confusion of explanation of the title subject. The low dose is defined roughly lower than 200 mGy and low dose rate, 0.05 mGy/min. The health effect is evaluated from 2 aspects of clinical symptom/radiation hazard protection. In the clinical aspect, the effect is classified in physical (early and late) and genetic ones, and is classified in stochastic (no threshold value, TV) and deterministic (with TV) ones from the radioprotection aspect. Although the absence of TV in the carcinogenic and genetic effects has not been proved, ICRP employs the stochastic standpoint from the safety aspect for radioprotection. The lowest human TV known now is 100 mGy, meaning that human deterministic effect would not be generated below this dose. Genetic deterministic effect can be observable only in animal experiments. These facts suggest that the practical risk of exposure to <100 mGy in human is the carcinogenesis. The relationship between carcinogenic risk in A-bomb survivors and their exposed dose are found fitted to the linear no TV model, but the epidemiologic data, because of restriction of subject number analyzed, do not always mean that the model is applicable even below the dose <100 mGy. This would be one of confusing causes in explanation: no carcinogenic risk at <100 mGy or risk linear to dose even at <100 mGy, neither of which is scientifically conclusive at present. Also mentioned is the scarce risk of cancer in residents living in the high background radiation regions in the world in comparison with that in the A-bomb survivors exposed to the chronic or acute low dose/dose rate. Molecular events are explained for the low-dose radiation-induced DNA damage and its repair, gene mutation and chromosome aberration, hypothesis of carcinogenesis by mutation, and non-targeting effect of radiation (bystander effect and gene instability). Further researches to elucidate the low dose

  20. Effect of extended exposure of low-dose radiation on autoimmune diseases of immunologically depressed MRL/MpJ-gld/gld mice

    International Nuclear Information System (INIS)

    Ootsuyama, A.; Okazaki, R.; Norimura, T.

    2000-01-01

    We analyzed alterations of splenic T cell subpopulations and amelioration of autoimmune disease of MRL/MpJ-gld/gld mice (MRL/gld mice) after the extended exposure to low-dose radiation (LDR). Four-month old MRL/gld mice were exposed to 0.05, 0.2 and 0.5 Gy/day for 4 weeks (5 days/week) with a total dose of 1, 4 and 10 Gy, respectively. The mice irradiated with 0.2 and 0.5 Gy/day showed an obvious decrease in the proportions of splenic CD4 - CD8 - T cells and remission of their autoimmune disease. In the mice irradiated with 0.2 Gy/day, apoptotic cells were found in the white pulp of the spleen after the last irradiation, but not in that of the treated MRL/MpJ-+/+ mice (MRL/wild type mice). It seems that the accumulated CD4 - CD8 - T cells are more sensitive to radiation than other T cell subpopulations and prone to apoptosis, and efficient elimination of abnormal CD4 - CD8 - T cells by radiation-induced apoptosis may lead to the amelioration of autoimmune disease. (author)

  1. Adaptive iterative dose reduction (AIDR) 3D in low dose CT abdomen-pelvis: Effects on image quality and radiation exposure

    International Nuclear Information System (INIS)

    Ang, W C; Hashim, S; Karim, M K A; Bahruddin, N A; Salehhon, N; Musa, Y

    2017-01-01

    The widespread use of computed tomography (CT) has increased the medical radiation exposure and cancer risk. We aimed to evaluate the impact of AIDR 3D in CT abdomen-pelvic examinations based on image quality and radiation dose in low dose (LD) setting compared to standard dose (STD) with filtered back projection (FBP) reconstruction. We retrospectively reviewed the images of 40 patients who underwent CT abdomen-pelvic using a 80 slice CT scanner. Group 1 patients ( n =20, mean age 41 ± 17 years) were performed at LD with AIDR 3D reconstruction and Group 2 patients ( n =20, mean age 52 ± 21 years) were scanned with STD using FBP reconstruction. Objective image noise was assessed by region of interest (ROI) measurements in the liver and aorta as standard deviation (SD) of the attenuation value (Hounsfield Unit, HU) while subjective image quality was evaluated by two radiologists. Statistical analysis was used to compare the scan length, CT dose index volume (CTDI vol ) and image quality of both patient groups. Although both groups have similar mean scan length, the CTDI vol significantly decreased by 38% in LD CT compared to STD CT ( p <0.05). Objective and subjective image quality were statistically improved with AIDR 3D ( p <0.05). In conclusion, AIDR 3D enables significant dose reduction of 38% with superior image quality in LD CT abdomen-pelvis. (paper)

  2. Risks of low dose ionising radiation exposures Riesgos derivados de la exposición a dosis bajas de radiación ionizante

    Directory of Open Access Journals (Sweden)

    Almudena Real Gallego

    2010-12-01

    Full Text Available Although ionising radiation has been shown to have several beneficial applications for humans, it can also produce detrimental effects in humans and the environment. To adequately protect man and environment from the potential harmful effects of ionising radiation, is essential to know in detail the biological effects produced by it, its characteristics and the various factors that influence these effects. That is the objective of this article, describe the current status of knowledge about biological effects induced by ionising radiation, with special emphasis on those effects occurring after low dose exposures.La radiación ionizante ha mostrado tener diversas aplicaciones beneficiosas para el hombre, pero también puede dañar la salud de las personas y el medio ambiente. Para proteger adecuadamente al hombre de los posibles efectos nocivos de la radiación ionizante es imprescindible conocer en detalle los efectos biológicos producidos por esta, sus características y los distintos factores que influyen en dichos efectos. Ese es el objetivo de este artículo: describir el estado actual del conocimiento sobre los efectos biológicos que puede producir la radiación ionizante, con especial énfasis en aquellos efectos que se producen tras la exposición a dosis bajas.

  3. Low-dose computed tomography scans with automatic exposure control for patients of different ages undergoing cardiac PET/CT and SPECT/CT.

    Science.gov (United States)

    Yang, Ching-Ching; Yang, Bang-Hung; Tu, Chun-Yuan; Wu, Tung-Hsin; Liu, Shu-Hsin

    2017-06-01

    This study aimed to evaluate the efficacy of automatic exposure control (AEC) in order to optimize low-dose computed tomography (CT) protocols for patients of different ages undergoing cardiac PET/CT and single-photon emission computed tomography/computed tomography (SPECT/CT). One PET/CT and one SPECT/CT were used to acquire CT images for four anthropomorphic phantoms representative of 1-year-old, 5-year-old and 10-year-old children and an adult. For the hybrid systems investigated in this study, the radiation dose and image quality of cardiac CT scans performed with AEC activated depend mainly on the selection of a predefined image quality index. Multiple linear regression methods were used to analyse image data from anthropomorphic phantom studies to investigate the effects of body size and predefined image quality index on CT radiation dose in cardiac PET/CT and SPECT/CT scans. The regression relationships have a coefficient of determination larger than 0.9, indicating a good fit to the data. According to the regression models, low-dose protocols using the AEC technique were optimized for patients of different ages. In comparison with the standard protocol with AEC activated for adult cardiac examinations used in our clinical routine practice, the optimized paediatric protocols in PET/CT allow 32.2, 63.7 and 79.2% CT dose reductions for anthropomorphic phantoms simulating 10-year-old, 5-year-old and 1-year-old children, respectively. The corresponding results for cardiac SPECT/CT are 8.4, 51.5 and 72.7%. AEC is a practical way to reduce CT radiation dose in cardiac PET/CT and SPECT/CT, but the AEC settings should be determined properly for optimal effect. Our results show that AEC does not eliminate the need for paediatric protocols and CT examinations using the AEC technique should be optimized for paediatric patients to reduce the radiation dose as low as reasonably achievable.

  4. IL6-174 G>C Polymorphism (rs1800795 Association with Late Effects of Low Dose Radiation Exposure in the Portuguese Tinea Capitis Cohort.

    Directory of Open Access Journals (Sweden)

    Paula Boaventura

    Full Text Available Head and neck cancers, and cardiovascular disease have been described as late effects of low dose radiation (LDR exposure, namely in tinea capitis cohorts. In addition to radiation dose, gender and younger age at exposure, the genetic background might be involved in the susceptibility to LDR late effects. The -174 G>C (rs1800795 SNP in IL6 has been associated with cancer and cardiovascular disease, nevertheless this association is still controversial. We assessed the association of the IL6-174 G>C SNP with LDR effects such as thyroid carcinoma, basal cell carcinoma and carotid atherosclerosis in the Portuguese tinea capitis cohort. The IL6-174 G>C SNP was genotyped in 1269 individuals formerly irradiated for tinea capitis. This sampling group included thyroid cancer (n = 36, basal cell carcinoma (n = 113 and cases without thyroid or basal cell carcinoma (1120. A subgroup was assessed for atherosclerosis by ultrasonography (n = 379 and included matched controls (n = 222. Genotypes were discriminated by real-time PCR using a TaqMan SNP genotyping assay. In the irradiated group, we observed that the CC genotype was significantly associated with carotid plaque risk, both in the genotypic (OR = 3.57, CI = 1.60-7.95, p-value = 0.002 and in the recessive (OR = 3.02, CI = 1.42-6.42, p-value = 0.004 models. Irradiation alone was not a risk factor for carotid atherosclerosis. We did not find a significant association of the IL6-174 C allele with thyroid carcinoma or basal cell carcinoma risk. The IL6-174 CC genotype confers a three-fold risk for carotid atherosclerotic disease suggesting it may represent a genetic susceptibility factor in the LDR context.

  5. Genome Wide Evaluation of Normal Human Tissue in Response to Controlled, In vivo Low-Dose Low LET Ionizing Radiation Exposure: Pathways and Mechanisms Final Report, September 2013

    Energy Technology Data Exchange (ETDEWEB)

    Rocke, David M. [University of California Davis

    2013-09-09

    During course of this project, we have worked in several areas relevant to low-dose ionizing radiation. Using gene expression to measure biological response, we have examined the response of human skin exposed in-vivo to radation, human skin exposed ex-vivo to radiation, and a human-skin model exposed to radiation. We have learned a great deal about the biological response of human skin to low-dose ionizing radiation.

  6. Very Low Dose Fetal Exposure to Chernobyl Contamination Resulted in Increases in Infant Leukemia in Europe and Raises Questions about Current Radiation Risk Models

    Directory of Open Access Journals (Sweden)

    Christopher C. Busby

    2009-12-01

    Full Text Available Following contamination from the Chernobyl accident in April 1986 excess infant leukemia (0–1 y was reported from five different countries, Scotland, Greece, Germany, Belarus and Wales and Scotland combined. The cumulative absorbed doses to the fetus, as conventionally assessed, varied from 0.02 mSv in the UK through 0.06 mSv in Germany, 0.2 mSv in Greece and 2 mSv in Belarus, where it was highest. Nevertheless, the effect was real and given the specificity of the cohort raised questions about the safety of applying the current radiation risk model of the International Commission on Radiological Protection (ICRP to these internal exposures, a matter which was discussed in 2000 by Busby and Cato [7,8] and also in the reports of the UK Committee examining Radiation Risk from Internal Emitters. Data on infant leukemia in the United Kingdom, chosen on the basis of the cohorts defined by the study of Greece were supplied by the UK Childhood Cancer Research Group. This has enabled a study of leukemia in the combined infant population of 15,466,845 born in the UK, Greece, and Germany between 1980 and 1990. Results show a statistically significant excess risk RR = 1.43 (95% CI 1.13 < RR < 1.80 (2-tailed; p = 0.0025 in those born during the defined peak exposure period of 01/07/86 to 31/12/87 compared with those born between 01/01/80 and 31/12/85 and 01/01/88 and 31/12/90. The excess risks in individual countries do not increase monotonically with the conventionally calculated doses, the relation being biphasic, increasing sharply at low doses and falling at high doses. This result is discussed in relation to fetal/cell death at higher doses and also to induction of DNA repair. Since the cohort is chosen specifically on the basis of exposure to internal radionuclides, the result can be expressed as evidence for a significant error in the conventional modeling for such internal fetal exposures.

  7. Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

    Science.gov (United States)

    Li, Yuan; Ge, Chang; Feng, Guoxing; Xiao, Huiwen; Dong, Jiali; Zhu, Changchun; Jiang, Mian; Cui, Ming; Fan, Saijun

    2018-03-24

    Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings. © 2018 Wiley Periodicals, Inc.

  8. Low dose irradiation and biological defense mechanisms

    International Nuclear Information System (INIS)

    Sugahara, Tsutomu; Sagan, L.A.; Aoyama, Takashi

    1992-01-01

    It has been generally accepted in the context of radiation protection that ionizing radiation has some adverse effect even at low doses. However, epidemiological studies of human populations cannot definitively show its existence or absence. Furthermore, recent studies of populations living in areas of different background radiation levels reported some decrease in adverse health effects at high background levels. Genetic studies of atomic bomb survivors failed to produce statistically significant findings on the mutagenic effects of ionizing radiation. A British study however, suggests that a father's exposure to low dose radiation on the job may increase his children's risk of leukemia. On the other hand, many experimental studies have raised the possibility that low doses of ionizing radiation may not be harmful or may even produce stimulating or adaptive responses. The term 'hormesis' has come to be used to describe these phenomena produced by low doses of ionizing radiation when they were beneficial for the organisms studied. At the end of the International Conference on Low Dose Irradiation one conclusion appeared to be justified: radiation produces an adaptive response, though it is not universally detected yet. The conference failed to obtain any consensus on risk assessment at low doses, but raised many problems to be dealt with by future studies. The editors therefore believe that the Proceedings will be useful for all scientists and people concerned with radiation protection and the biological effects of low-dose irradiation

  9. Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice.

    Science.gov (United States)

    Feng, Yu; Tian, Jijing; Xie, Heidi Qunhui; She, Jianwen; Xu, Sherry Li; Xu, Tuan; Tian, Wenjing; Fu, Hualing; Li, Shuaizhang; Tao, Wuqun; Wang, Lingyun; Chen, Yangsheng; Zhang, Songyan; Zhang, Wanglong; Guo, Tai L; Zhao, Bin

    2016-09-01

    Although the chlorinated flame retardant Dechlorane (Dec) 602 has been detected in food, human blood, and breast milk, there is limited information on potential health effects, including possible immunotoxicity. We determined the immunotoxic potential of Dec 602 in mice by examining the expression of phenotypic markers on thymocyte and splenic lymphocyte subsets, Th1/Th2 transcription factors, and the production of cytokines and antibodies. Adult male C57BL/6 mice were orally exposed to environmentally relevant doses of Dec 602 (1 and 10 μg/kg body weight per day) for 7 consecutive days. Thymocyte and splenic CD4 and CD8 subsets and splenocyte apoptosis were examined by flow cytometric analysis. Cytokine expression was measured at both the mRNA and the protein levels. Levels of the transcription factors Th1 (T-bet and STAT1) and Th2 (GATA3) were determined using quantitative real-time polymerase chain reaction (qPCR). Serum levels of immunoglobulins IgG1, IgG2a, IgG2b and IgE were measured by enzyme-linked immunosorbent assay (ELISA). Splenic CD4+ and CD8+ T cell subsets were decreased compared with vehicle controls, and apoptosis was significantly increased in splenic CD4+ T cells. Expression (mRNA and protein) of Th2 cytokines [interleukin (IL)-4, IL-10, and IL-13] increased, and that of Th1 cytokines [IL-2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] decreased. The Th2 transcriptional factor GATA3 increased, whereas the Th1 transcriptional factors T-bet and STAT1 decreased. As additional indicators of the Th2-Th1 imbalance, production of IgG1 was significantly increased, whereas IgG2a was reduced. To our knowledge, we are the first to report evidence of the effects of Dec 602 on immune function in mice, with findings indicating that Dec 602 exposure favored Th2 responses and reduced Th1 function. Feng Y, Tian J, Xie HQ, She J, Xu SL, Xu T, Tian W, Fu H, Li S, Tao W, Wang L, Chen Y, Zhang S, Zhang W, Guo TL, Zhao B. 2016. Effects of acute low-dose

  10. LOW DOSE RISK, DECISIONS, and RISK COMMUNICATION

    International Nuclear Information System (INIS)

    Flynn, James

    2002-01-01

    The objective of this project is to conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low-dose exposures. Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low-dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

  11. Impact of low-dose chronic exposure to Bisphenol A (BPA) on adult male zebrafish adaption to the environmental complexity: Disturbing the color preference patterns and reliving the anxiety behavior.

    Science.gov (United States)

    Li, Xiang; Sun, Ming-Zhu; Li, Xu; Zhang, Shu-Hui; Dai, Liang-Ti; Liu, Xing-Yu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2017-11-01

    The extensive usage of xenobiotic endocrine disrupting chemicals (XEDCs), such as Bisphenol A (BPA), has created obvious threat to aquatic ecosystems worldwide. Although a comprehensive understanding of the adverse effect of BPA on behaviors and physiology have been proven, the potential impact of low-dose BPA on altering the basic ability of aquatic organism in adapting to the surrounded complex environment still remains elusive. In this research, we report that treatment of adult male zebrafish with chronic (7 weeks) low-dose (0.22 nM-2.2 nM) BPA, altered the ability in adapting the complex environment by disturbing the natural color preference patterns. In addition, chronic 50 ng/L (0.22 nM) BPA exposure alleviated the anxiety behavior of male zebrafish confronted with the novel environment by enhancing the preference towards light in the light/dark preference test. This phenotype was associated with less expression of serotonin (5-TH) in the hypothalamus and the down-regulation of tyrosine hydroxylase (TH) in brain tissues. As such, our results show that low-dose BPA remnant in surface waters altered zebrafish behavior that are known to have ecological and evolutionary consequences. Here we reported that the impact of chronic low-dose BPA exposure on the basic capability of zebrafish to adapt to the environmental complexity. Specifically, BPA at low concentration, under the environmental safety level and 3000-fold lower than the accepted human daily exposure, interfered with the ability to discriminate color and alleviate anxiety induced by the novel environment, which finally altered the capability of male zebrafish to adapt to the environmental complexity. These findings revealed the ecological effect of low-dose BPA and regular BPA concentration standard are not necessarily safe. The result also provided the consideration of retuning the hazard concentration level of BPA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Image evaluation and exposure dose with the application of tube voltage and adaptive statistical iterative reconstruction of low dose computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Tae Joon [Dept. of Radiology, Konkuk University Medical Center, Seoul (Korea, Republic of); Kim, Ki Jeong [Dept. of Radiology, Wonkwang University Hospital, Iksan (Korea, Republic of); Lee, Hye Nam [Dept. of Radiology, Gimsangyeong Internal Medicine Clinic, Nonsan (Korea, Republic of)

    2017-06-15

    The study has attempted to evaluate and compare the image evaluation and exposure dose by respectively applying filter back projection (FBP), the existing test method, and adaptive statistical iterative reconstruction (ASIR) with different values of tube voltage during the low dose computed tomography (LDCT). With the image reconstruction method as basis, chest phantom was utilized with the FBP and ASIR set at 10%, 20% respectively, and the change of tube voltage (100 kVp, 120 kVp). For image evaluation, back ground noise, signal-noise ratio (SNR) and contrast-noise ratio (CNR) were measured, and, for dose assessment, CTDIvol and DLP were measured respectively. In terms of image evaluation, there was significant difference in ascending aorta (AA) SNR and inpraspinatus muscle (IM) SNR with the different amount of tube voltage (p < 0.05). In terms of CTDIvol, the measured values with the same tube voltage of 120 kVp were 2.6 mGy with no-ASIR and 2.17 mGy with 20%-ASIR respectively, decreased by 0.43 mGy, and the values with 100 kVp were 1.61 mGy with no-ASIR and 1.34 mGy with 20%-ASIR, decreased by 0.27 mGy. In terms of DLP, the measured values with 120 kVp were 103.21 mGy‧cm with no-ASIR and 85.94 mGy‧cm with 20%-ASIR, decreased by 17.27mGy‧cm (about 16.7%), and the values with 100 kVp were 63.84 mGy‧cm with no-ASIR and 53.25 mGy‧cm with 20%-ASIR, a decrease by 10.62 mGy‧cm ( about 16.7%). At lower tube voltage, the rate of dose significantly decreased, but the negative effects on image evaluation was shown due to the increase of noise.

  13. Image evaluation and exposure dose with the application of tube voltage and adaptive statistical iterative reconstruction of low dose computed tomography

    International Nuclear Information System (INIS)

    Moon, Tae Joon; Kim, Ki Jeong; Lee, Hye Nam

    2017-01-01

    The study has attempted to evaluate and compare the image evaluation and exposure dose by respectively applying filter back projection (FBP), the existing test method, and adaptive statistical iterative reconstruction (ASIR) with different values of tube voltage during the low dose computed tomography (LDCT). With the image reconstruction method as basis, chest phantom was utilized with the FBP and ASIR set at 10%, 20% respectively, and the change of tube voltage (100 kVp, 120 kVp). For image evaluation, back ground noise, signal-noise ratio (SNR) and contrast-noise ratio (CNR) were measured, and, for dose assessment, CTDIvol and DLP were measured respectively. In terms of image evaluation, there was significant difference in ascending aorta (AA) SNR and inpraspinatus muscle (IM) SNR with the different amount of tube voltage (p < 0.05). In terms of CTDIvol, the measured values with the same tube voltage of 120 kVp were 2.6 mGy with no-ASIR and 2.17 mGy with 20%-ASIR respectively, decreased by 0.43 mGy, and the values with 100 kVp were 1.61 mGy with no-ASIR and 1.34 mGy with 20%-ASIR, decreased by 0.27 mGy. In terms of DLP, the measured values with 120 kVp were 103.21 mGy‧cm with no-ASIR and 85.94 mGy‧cm with 20%-ASIR, decreased by 17.27mGy‧cm (about 16.7%), and the values with 100 kVp were 63.84 mGy‧cm with no-ASIR and 53.25 mGy‧cm with 20%-ASIR, a decrease by 10.62 mGy‧cm ( about 16.7%). At lower tube voltage, the rate of dose significantly decreased, but the negative effects on image evaluation was shown due to the increase of noise

  14. Aberrant cell divisions in root meristeme of maize following exposure to X-rays low doses compared to similar effects of 50 Hz electromagnetic exposure

    Directory of Open Access Journals (Sweden)

    Luchian T.

    2012-04-01

    Full Text Available The response of maize to radiation exposure was investigated by two cytogenetic methods considering the importance of the geno-toxic effect for environmental and agricultural purposes. Uniform genophond seeds, freshly germinated, were exposed to relatively low radiation doses using a radiotherapy X-ray applicator from a hospital irradiation device and to a 50 Hz electromagnetic field with about 10 mT magnetic induction (generated within laboratory assembled electromagnetic coils. Radicular meristeme tissue aliquots were prevailed for cytogenetic investigation based on microscopic observations and cell counting. Microscope slides were prepared following a specific procedure (squash technique and Feulgen method based on modified Carr reactive coloration. Mitotic index as well as chromosomal aberration percentage were calculated for more than 30,000 cells taken into account. From a qualitative viewpoint, chromosomal aberrations such as interchromatidian bridges, lagging and expelled chromosomes and multipolar divisions were evidenced - no distinct situation for either ionizing radiation or electromagnetic field being identified. The main quantitative difference consisted in the increased mitotic index for electromagnetic exposure increased times compared with the diminished mitotic index in the case of low X-ray doses.

  15. Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats

    International Nuclear Information System (INIS)

    Zhuang Jianguo; Xu Fadi; Campen, Matthew J.; Zhang Cancan; Pena-Philippides, Juan C.; Sopori, Mohan L.

    2008-01-01

    Sarin, a highly toxic nerve gas, is believed to cause bronchoconstriction and even death primarily through respiratory failure; however, the mechanism underlying the respiratory failure is not fully understood. The goals of this study were to ascertain whether sarin affects baseline ventilation (V E ) and V E chemoreflexes as well as airway resistance and, if so, whether these changes are reversible. Four groups of F344 rats were exposed to vehicle (VEH) or sarin at 2.5, 3.5, and 4.0 mg h m -3 (SL, SM, and SH, respectively). V E and V E responses to hypercapnia (7% CO 2 ) or hypoxia (10% O 2 ) were measured by plethysmography at 2 h and 1, 2, and 5 days after VEH or sarin exposure. Total pulmonary resistance (R L ) also was measured in anesthetized VEH- and SH-exposed animals 2 h after exposure. Our results showed that within 2 h after exposure 11% of the SM- and 52% of the SH- exposed groups died. Although the SM and SH significantly decreased hypercapnic and hypoxic V E to similar levels (64 and 69%), SH induced greater respiratory impairment, characterized by lower baseline V E (30%; P E impairment recovered within 1-2 days after sarin exposure; interestingly, SH did not significantly affect baseline R L . Moreover, sarin induced body tremors that were unrelated to the changes in the V E responses. Thus, LC 50 sarin causes a reversible impairment of V E that is not dependent on the sarin-induced body tremors and not associated with changes in R L

  16. Exposure to low-dose X-rays promotes peculiar autophagic cell death in Drosophila melanogaster, an effect that can be regulated by the inducible expression of Hml dsRNA

    Energy Technology Data Exchange (ETDEWEB)

    Kanao, Tomoko [Department of Radiological Sciences, International University of Health and Welfare, Kitakanemaru 2600-1, Ohtawara-shi, Tochigi-ken 324-8501 (Japan); Miyachi, Yukihisa [Department of Radiological Sciences, International University of Health and Welfare, Kitakanemaru 2600-1, Ohtawara-shi, Tochigi-ken 324-8501 (Japan)]. E-mail: ymiyachi@iuhw.ac.jp

    2006-03-20

    We previously reported that to induce an early emergence effect with low-dose X-irradiation in Drosophila, exposure during the prepupae stage is necessary. The present study examined the mechanism by which low-dose radiation rapidly eliminates larval cells and activates the formation of the imaginal discs during metamorphosis. Upon exposure to 0.5 Gy X-rays at 2 h after puparium formation (APF), the larval salivary glands swelled and were surrounded by remarkably thick structures containing an acid phosphatase (Acph) enzyme, implicating a peculiar autophagic cell death. TUNEL staining revealed the presence of DNA fragmentations compared with cells from sham controls which remained unchanged until 12 h APF. Additionally, the salivary glands of exposed flies were completely destroyed by 10 h APF. Furthermore, exposure to 0.5 Gy X-rays also facilitated the activity of the engulfment function of dendritic cells (DCs); they were generated in the larval salivary glands, engulfed the cell corpses and finally moved to the fat body. Data from an experiment demonstrating the inducible expression of Hml double-stranded RNA (dsRNA) indicate that a slow rate of engulfment of larval cells results in a longer time to emergence. Thus, the animals subjected to low-dose X-rays activated autophagic processes, resulting in significantly faster adult eclosion.

  17. Exposure to low-dose X-rays promotes peculiar autophagic cell death in Drosophila melanogaster, an effect that can be regulated by the inducible expression of Hml dsRNA

    International Nuclear Information System (INIS)

    Kanao, Tomoko; Miyachi, Yukihisa

    2006-01-01

    We previously reported that to induce an early emergence effect with low-dose X-irradiation in Drosophila, exposure during the prepupae stage is necessary. The present study examined the mechanism by which low-dose radiation rapidly eliminates larval cells and activates the formation of the imaginal discs during metamorphosis. Upon exposure to 0.5 Gy X-rays at 2 h after puparium formation (APF), the larval salivary glands swelled and were surrounded by remarkably thick structures containing an acid phosphatase (Acph) enzyme, implicating a peculiar autophagic cell death. TUNEL staining revealed the presence of DNA fragmentations compared with cells from sham controls which remained unchanged until 12 h APF. Additionally, the salivary glands of exposed flies were completely destroyed by 10 h APF. Furthermore, exposure to 0.5 Gy X-rays also facilitated the activity of the engulfment function of dendritic cells (DCs); they were generated in the larval salivary glands, engulfed the cell corpses and finally moved to the fat body. Data from an experiment demonstrating the inducible expression of Hml double-stranded RNA (dsRNA) indicate that a slow rate of engulfment of larval cells results in a longer time to emergence. Thus, the animals subjected to low-dose X-rays activated autophagic processes, resulting in significantly faster adult eclosion

  18. Low doses effects and gamma radiations low dose rates

    International Nuclear Information System (INIS)

    Averbeck, D.

    1999-01-01

    This expose wishes for bringing some definitions and base facts relative to the problematics of low doses effects and low dose rates effects. It shows some already used methods and some actual experimental approaches by focusing on the effects of ionizing radiations with a low linear energy transfer. (N.C.)

  19. Carcinogenesis induced by low-dose radiation

    Directory of Open Access Journals (Sweden)

    Piotrowski Igor

    2017-11-01

    Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

  20. Epigenomic Adaptation to Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gould, Michael N. [Univ. of Wisconsin, Madison, WI (United States)

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  1. Hemo rheological Changes Associated with Occupational Exposure to Low Doses Radiation from X-Ray Inspection Machines Influenced by Smoking Habits

    International Nuclear Information System (INIS)

    Ahmed, M.A.M.; El-khatib, A.M.; Naim, M.A.; Ali, F.M.

    2011-01-01

    The effects of low dose x-ray radiation on some rheological parameters of blood were investigated in 30 male x-ray workers and 20 healthy volunteers not occupationally exposed to any type of radiation and match in age. Each group was classified according to smoking habits. The analysis of the flow curve of all subjects was performed by applying power-law model and Bingham plastic model. The results indicated elevates in whole blood viscosity and yield stress in smoker subjects as compared with non-smoker subjects and also showed that the elevation of blood viscosity of smoker radiation workers are related to work duration in the radiation field.We have observed that cigarette smoking increases the hazardous effects of radiation through the increase of blood viscosity, which excess the risk of cardiovascular disease. So it is recommended to consider blood viscosity measurements to be included in routine medical investigation for occupational workers and rheological

  2. Estimate of radiation detriment long period after exposure to low doses of ionizing radiation: Chromosomal aberrations in liquidators 6-10 years after the Chernobyl accident

    International Nuclear Information System (INIS)

    Nikiforov, A.M.; Slozina, N.M.; Neronova, E.G.; Kharchenko, T.V.; Drygina, L.B.; Strukov, E.L.

    1997-01-01

    The group of 297 liquidators was cytogenetically investigated 6 - 10 years after the Chernobyl accident. The significantly increased level of chromosomal and chromatid types exchange aberrations was shown. For all subjects questionnaires that provide consideration of known and suspected confounding variables were filled in. The participation in recovery works at the Chernobyl nuclear power station was the only reason for dicentrics and rings rise in liquidators. An investigation of the tumor-specific markers (CEA, AFP, CA19-9, PSA, NSE) was carried out in 56 liquidators simultaneously with chromosomal analysis. The increased level of NSE was found in liquidators bearing the chromosomal aberrations of exchange type. The results of this work let us to consider the liquidators who underwent to low doses of ionizing radiation 6-10 years ago as a detrimental group that needs special scientific and medical attention. (author)

  3. Study of genomic instability induced by low dose ionizing radiation

    International Nuclear Information System (INIS)

    Seoane, A.; Crudeli, C.; Dulout, F.

    2006-01-01

    The crews of commercial flights and services staff of radiology and radiotherapy from hospitals are exposed to low doses of ionizing radiation. Genomic instability includes those adverse effects observed in cells, several generations after the exposure occurred. The purpose of this study was to analyze the occurrence of genomic instability by very low doses of ionizing radiation [es

  4. Radiation effects of high and low doses

    International Nuclear Information System (INIS)

    El-Naggar, A.M.

    1998-01-01

    The extensive proliferation of the uses and applications of atomic and nuclear energy resulted in possible repercussions on human health. The prominent features of the health hazards that may be incurred after exposure to high and low radiation doses are discussed. The physical and biological factors involved in the sequential development of radiation health effects and the different cellular responses to radiation injury are considered. The main criteria and features of radiation effects of high and low doses are comprehensively outlined

  5. Status of calcium regulating hormonal systems in delayed period in persons exposed to occupational exposure of low doses of ionizing radiations

    International Nuclear Information System (INIS)

    Dospolova, Zh.G.; Abylaev, Zh.A.

    1997-01-01

    Purpose of study is consideration of endocrine system participation in development of calcium exchange disorders in persons exposed to action of low dose radiation . By radio- immune method in blood serum of 150 liquidators of Chernobyl accident consequences the concentration the following hormones were determined: parathormone, T 3 , T 4 , TSH, cortisol, ACTH, testosteron, insulin. Content of these hormones have been studied in according to following radiation factors: value of absorbed doses of external irradiation, degree of radioactive contamination of zone and exposition duration. It was determined, that basically dishormone disorders development have been concerned with parathormone, cortisol, hormones of thyroid axis, and in some cases to ACTH and insulin. Liquidators' frequencies of normal and changed concentration of calcium regulating hormones are sited in tabular form. It was established, that examined persons in result hormone disorders have of decrease functions of pituitary glands (76.78 %), pancreas (55 %), thyroid gland (24.31 %) and sex glands (19.23 %) and simultaneously cases of increase functions of parathyroid gland (58.2 %), adrenal glands (52.32 %) and adeno-pituitary glands (17.39). It is concluded, that inter hormonal correlation disorders are accompanying with morphologic and functional futures of secretory activity changes

  6. Damage to the testes of a marine fish, the plaice (Pleuronectes platessa), induced by chronic exposure to low dose rate radiation

    International Nuclear Information System (INIS)

    Knowles, J.F.

    1999-01-01

    Although most authorised disposals of liquid radioactive waste are to the sea, effects of chronic radiation exposure on reproductive endpoints in a marine fish have not so far been investigated. For this reason we have carried out a series of experiments into effects of chronic radiation exposure on plaice, a commercially important marine food species which spends much of its life in contact with sea bed sediments where exposure from radioactive contaminants have been shown to be highest

  7. The Tokyo subway sarin attack-lessons learned

    International Nuclear Information System (INIS)

    Okumura, T.; Hisaoka, T.; Yamada, A.; Naito, T.; Isonuma, H.; Okumura, S.; Miura, K.; Sakurada, M.; Maekawa, H.; Ishimatsu, S.; Takasu, N.; Suzuki, K.

    2005-01-01

    The sarin gas attack in the Tokyo subway system is reviewed from a clinical toxicology perspective. Based on the lessons learned from this attack, the following areas should be addressed on a global scale. First, an adequate supply of protective equipment is required, including level B protective equipment with a pressure demand breathing apparatus. In addition, a system should be established that enables a possible cause to be determined based on symptoms, physical findings, general laboratory tests, and a simple qualitative analysis for poisonous substances. If an antidote is needed, the system should enable it to be administered to the victims as quickly as possible. Preparation for a large-scale chemical attack by terrorists requires the prior establishment of a detailed decontamination plan that utilizes not only mass decontamination facilities but also public facilities in the area. A system should be established for summarizing, evaluating, and disseminating information on poisonous substances. Finally, a large-scale scientific investigation of the Tokyo sarin attack should be conducted to examine its long-term and subclinical effects and the effects of exposure to asymptomatic low levels of sarin

  8. Changes in the Metabolome in Response to Low-Dose Exposure to Environmental Chemicals Used in Personal Care Products during Different Windows of Susceptibility

    NARCIS (Netherlands)

    Houten, Sander M.; Chen, Jia; Belpoggi, Fiorella; Manservisi, Fabiana; Sánchez-Guijo, Alberto; Wudy, Stefan A.; Teitelbaum, Susan L.

    2016-01-01

    The consequences of ubiquitous exposure to environmental chemicals remain poorly defined. Non-targeted metabolomic profiling is an emerging method to identify biomarkers of the physiological response to such exposures. We investigated the effect of three commonly used ingredients in personal care

  9. Drinking-water exposure to a mixture of nitrate and low-dose atrazine metabolites and small-for-gestational age (SGA) babies: a historic cohort study.

    Science.gov (United States)

    Migeot, V; Albouy-Llaty, M; Carles, C; Limousi, F; Strezlec, S; Dupuis, A; Rabouan, S

    2013-04-01

    Groundwater, surface water and drinking water are contaminated by nitrates and atrazine, an herbicide. They are present as a mixture in drinking water and with their endocrine-disrupting activity, they may alter fetal growth. To study an association between drinking-water atrazine metabolites/nitrate mixture exposure and small-for-gestational-age(SGA). A historic cohort study based on birth records and drinking-water nitrate and pesticide measurements in Deux-Sèvres (France) between 2005 and 2009 was carried out. Exposure to drinking-water atrazine metabolites/nitrate mixture was divided into 6 classes according to the presence or absence of atrazine metabolites and to terciles of nitrate concentrations in each trimester of pregnancy. Regression analysis of SGA by mixture exposure at second trimester was subsequently conducted. We included 11,446 woman-neonate couples of whom 37.0% were exposed to pesticides, while 99.9% of the women were exposed to nitrates. Average nitrate concentration was from 0 to 63.30 mg/L. In the second trimester of pregnancy, the risk of SGA was different with mixture exposure when drinking-water atrazine metabolites, mainly 2 hydroxyatrazine and desethylatrazine, were present and nitrate dose exposure increased: compared to single first tercile of nitrate concentration exposure, single second tercile exposure OR was 1.74 CI 95% [1.10; 2.75] and atrazine metabolites presence in the third tercile of nitrate concentration exposure OR was 0.87 CI 95% [0.45;1.67]. It is possible that the association found at the second trimester of exposure with regard to birth weight may likewise be observed before birth, with regard to the estimated fetal weight, and that it might change in the event that the atrazine metabolites dose were higher or the nitrate dose lower. It would appear necessary to further explore the variability of effects. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  10. Immediate and Delayed Drug Therapy Effects on Low Dose Sarin Exposed Mice Myocardial Performance

    Science.gov (United States)

    2011-03-01

    studied using electrocardiography ( EKG ) and histological/immunochemical techniques (staining with hematoxylin/eosin and brain natriuretic peptide, BNP...size and BNP levels than controls (p = 0.001). EKGs showed T-wave anomalies. These results are indicators of cardiac insult. The second treatment...mice include being able to only take short time interval readings and the development of movement artifacts in the recordings. To prevent issues

  11. Neuroimmune Interactions, Low-Dose Sarin Inhalation, and Gulf War Syndrome

    Science.gov (United States)

    2012-10-01

    pathogen-free Lewis (LEW) rats were purchased from Harlan Sprague-Dawley Farms (Branchburg, NJ, USA), and IL-1 receptor knockout (IL-1R KO) mice and...activities were quenched with 3% H2O2 in methanol for 15 min at room temperature (RT). The tissue sections were blocked with 2% normal goat serum in PBS...Sections were then washed (6x for 5 min each) in PBS with 0.2% Triton and incubated for 30 min at RT with goat anti-rabbit (1:200 dilution; Cat# BA

  12. Multidisciplinary European Low Dose Initiative (MELODI). Strategic research agenda for low dose radiation risk research

    Energy Technology Data Exchange (ETDEWEB)

    Kreuzer, M. [Federal Office for Radiation Protection, BfS, Department of Radiation Protection and Health, Neuherberg (Germany); Auvinen, A. [University of Tampere, Tampere (Finland); STUK, Helsinki (Finland); Cardis, E. [ISGlobal, Barcelona Institute for Global Health, Barcelona (Spain); Durante, M. [Institute for Fundamental Physics and Applications, TIFPA, Trento (Italy); Harms-Ringdahl, M. [Stockholm University, Centre for Radiation Protection Research, Stockholm (Sweden); Jourdain, J.R. [Institute for Radiological Protection and Nuclear Safety, IRSN, Fontenay-aux-roses (France); Madas, B.G. [MTA Centre for Energy Research, Environmental Physics Department, Budapest (Hungary); Ottolenghi, A. [University of Pavia, Physics Department, Pavia (Italy); Pazzaglia, S. [Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Rome (Italy); Prise, K.M. [Queens University Belfast, Belfast (United Kingdom); Quintens, R. [Belgian Nuclear Research Centre, SCK-CEN, Mol (Belgium); Sabatier, L. [French Atomic Energy Commission, CEA, Paris (France); Bouffler, S. [Public Health England, PHE, Chilton (United Kingdom)

    2018-03-15

    MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website (http://www.melodi-online.eu/sra.html). (orig.)

  13. Consequences of the exposure at low dose rates-contribution of animal experimentation. Consequences de l'exposition aux faibles debits de dose. Apport de l'experimentation animale

    Energy Technology Data Exchange (ETDEWEB)

    Masse, R. (CEA Centre d' Etudes de Fontenay-aux-Roses, 92 (FR). Direction des Sciences du Vivant)

    1990-01-01

    The exposure of laboratory animals to the various types of radiations will induce cancers in relation with the tissue absorbed doses. The shape of the dose-effet relationship is most variable. It is important to distinguish which tumours are comparable to human tumours. Those showing more analogies answer but seldom to the classical lineo-quadratic relationship; however, a strong attenuation of induction is demonstrated at low dose rates. Quasi-threshold relationships are seen after the exposure of some tissues to high-LET radiations. These observations question the validity of generalizing the radiobiologists' dual action theory, setting the origin of the dose-effect relationship in the induction of events within the DNA molecule. There is an alternative in the cellular collaboration events; it assumes that the effectiveness per dose unit decreases constantly as an inverse function of the dose rate.

  14. Mammography-oncogenecity at low doses

    International Nuclear Information System (INIS)

    Heyes, G J; Mill, A J; Charles, M W

    2009-01-01

    dose exposure, it is not a low dose rate examination, and protraction of dose should not be confused with fractionation. Although there is potential for a suppressive effect at low doses, recent epidemiological data, and several international radiation risk assessments, continue to promote the linear no-threshold (LNT) model. Finally, recent studies have shown that magnetic resonance imaging (MRI) is more sensitive than mammography in detecting invasive breast cancer in women with a genetic sensitivity. Since an increase in the risk associated with mammographic screening would blur the justification of exposure for this high risk subgroup, the use of other (non-ionising) screening modalities is preferable.

  15. Initial oxidation of TiFe1−xMnx (x = 0–0.3) by low dose exposures to H2O and O2

    International Nuclear Information System (INIS)

    Shwartz, A.; Shamir, N.; Froumin, N.; Zalkind, S.; Edry, I.; Haim, A.; Mintz, M.H.

    2014-01-01

    Highlights: • Thermodynamics of adsorption and initial oxidation of TiFe 1−x Mn x by H 2 O versus O 2 . • Explanation of different oxide formations. • Explanation of the role of the different constituents of the alloys in the processes. - Abstract: The very initial room-temperature oxidation processes of the ternary pseudo-binary TiFe 1−x Mn x (x = 0–0.3) intermetallics by trace amounts of H 2 O vapor and O 2 were studied utilizing XPS and AES techniques. Different reactivities of the two gases were obtained, with a lower oxidation ability of H 2 O, relative to O 2 , as anticipated from thermodynamic considerations. The exposure to O 2 results in a two stage oxidation of the Ti ingredient, which first converts into a divalent TiO (up to exposures of about 2 L), then proceeds into a tetravalent TiO 2 form. Unlike oxygen, water exposure produces only the divalent oxide through the whole exposure range studied (11 L). The Mn component in these compounds is oxidized only by O 2 and not by H 2 O. The Fe ingredient is not oxidized at all and remains in its metallic form up to exposures of 30 L

  16. Low dose prenatal ethanol exposure induces anxiety-like behaviour and alters dendritic morphology in the basolateral amygdala of rat offspring.

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    Full Text Available Prenatal exposure to high levels of alcohol is strongly associated with poor cognitive outcomes particularly in relation to learning and memory. It is also becoming more evident that anxiety disorders and anxiety-like behaviour can be associated with prenatal alcohol exposure. This study used a rat model to determine if prenatal exposure to a relatively small amount of alcohol would result in anxiety-like behaviour and to determine if this was associated with morphological changes in the basolateral amygdala. Pregnant Sprague Dawley rats were fed a liquid diet containing either no alcohol (Control or 6% (vol/vol ethanol (EtOH throughout gestation. Male and Female offspring underwent behavioural testing at 8 months (Adult or 15 months (Aged of age. Rats were perfusion fixed and brains were collected at the end of behavioural testing for morphological analysis of pyramidal neuron number and dendritic morphology within the basolateral amygdala. EtOH exposed offspring displayed anxiety-like behaviour in the elevated plus maze, holeboard and emergence tests. Although sexually dimorphic behaviour was apparent, sex did not impact anxiety-like behaviour induced by prenatal alcohol exposure. This increase in anxiety - like behaviour could not be attributed to a change in pyramidal cell number within the BLA but rather was associated with an increase in dendritic spines along the apical dendrite which is indicative of an increase in synaptic connectivity and activity within these neurons. This study is the first to link increases in anxiety like behaviour to structural changes within the basolateral amygdala in a model of prenatal ethanol exposure. In addition, this study has shown that exposure to even a relatively small amount of alcohol during development leads to long term alterations in anxiety-like behaviour.

  17. Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: Assessment by real-time PCR array

    Science.gov (United States)

    Arsenic contamination in drinking water has become a great public health concern worldwide. Chronic arsenic exposure results in higher risk of skin, lung and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects o...

  18. Radiation Risk from Chronic Low Dose-Rate Radiation Exposures: The Role of Life-Time Animal Studies - Workshop October 2005

    Energy Technology Data Exchange (ETDEWEB)

    Gayle Woloschak

    2009-12-16

    As a part of Radiation research conference, a workshop was held on life-long exposure studies conducted in the course of irradiation experiements done at Argonne National Laboratory between 1952-1992. A recent review article documents many of the issues discussed at that workshop.

  19. Near-term and late biological effects of acute and low-dose-rate continuous gamma-ray exposure in dogs and monkeys

    International Nuclear Information System (INIS)

    Spalding, J.F.; Holland, L.M.

    1979-07-01

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (inury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with gamma rays at 35 r/day until death to determine the amount of radiation-induced injry remaining in conditioned animals as a reduction in mean survival time. Dogs (50%) and monkeys (8%) died from injury incurred during conditioning exposures. Thus, the comparative response (in terms of lethality) of dogs and monkeys to dose protraction by acute dose fractionation was similar to what we would expect from a single acute dose. The mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approx. 1400 h). Thus, the hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35-R/day gamma-ray challenge exposure were greater (significant in dogs but not in monkeys) than for their control counterparts. Thus, long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than 4 times the acute LD 50 30 in dogs and approximately 2 times that in monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 Rat/day

  20. New radiobiological findings bearing on the 1977 ICRP recommendations. [Sensitivity of mouse and monkey prenatal oocytes to chronic, low-dose, tritium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Dobson, R.L.

    1979-02-14

    Recent experiments on low-level irradiation during development raise questions relevant to ICRP Publication 26. Mice and monkeys were studied; the measured endpoint was the radiation-induced loss of female germ cells. Three issues are examined. The first is the numerical value of Q (quality factor) appropriate for low-energy beta rays. Comparisons of tritium with gamma radiation were made under conditions of chronic, low-level exposure, and the relative biological effectiveness (RBE) was found to approach 3. Its bearing on ICRP's recommendations concerning Q applicable to tritium is discussed. Second, female germ cells in squirrel monkeys before birth were discovered to be extraordinarily radiosensitive, more easily destroyed than those of mice. If this holds for other primates too, it has radiation-protection implications hitherto overlooked. Third, the contrast between massive germ-cell loss from chronic exposure in prenatal squirrel monkeys and reported radioresistance of oocytes to acute exposure in rhesus monkeys, unless due to species difference, suggests that during development protracted irradiation may be especially injurious. This also could have important radiation-protection implications and is under investigation. (ERB)

  1. Low dose irradiation reduces cancer mortality rates

    International Nuclear Information System (INIS)

    Luckey, T.D.

    2000-01-01

    . Increased production of many molecules (interleukins, interferons, leukotrienes, chemotactic agents, and mitogens) related to immunity are found in mice exposed to low dose irradiation (Lim, S.-Z., Biologic Effects of Low Level Exposures to Radiation and Related Agents, pp.15-16, 1993). Those plus many enzymes and cofactors are inter- and intra-cellular agents involved in gene expression, T-cell maturation, phagocytosis, signal transduction, antigen reception and antibody production. This basic science information has been utilized for cancer therapy in Japanese and United States clinics. With the usual radio-, chemo- and surgical therapy, the 10 year survival of non-Hodgkin's lymphoma was 59%; when this was augmented by low dose irradiation, survival was 80% (Sakamoto, K., ICONE-7 Abstracts, p 50-51, 1999). Low dose irradiation of the mid-section of the body was effective. This area includes many elements of the immune system: the spleen with its germinal centers and lymphoid follicles, the liver with its phagocytosing Kupffer cells, kidney phagocytes, and the lamina propria and Peyer's patches of the intestinal wall. Irradiation of either the head and chest or the groin-legs area was unresponsive. Chronic low dose irradiation redness premature cancer mortality 51%. Standards should be revised with health, not risks, as the goal. Safe supplementation with ionizing radiation would provide a new plateau of health for people and wealth for nations. (author)

  2. Modification of damage following low doses

    International Nuclear Information System (INIS)

    Braby, L.A.; Nelson, J.M.; Metting, N.F.

    1988-01-01

    At very low doses the damage-interaction mechanism is responsible for very little lethal or potentially lethal damage, and repair of the latter should essentially disappear. An alternative model suggests that potentially lethal damage is either repaired with a constant half time or misrepaired at a rate which is proportional to the square of the damage concentration. In this case, as the dose decreases, the probability of misrepair decreases faster than the probability of repair, and repair becomes a more pronounced feature of the cell response. Since the consequence of unrepaired damage is an important question in determining the effects of low doses of radiation delivered at low dose rates, we have attempted to determine which of these two types of models is consistent with the response of plateau-phase CHO cells. In the earlier experiments, there was no indication of repair after a 50-rad exposure with a 24-hour split dose or plating delay; in fact, immediate plating resulted in survival slightly above control and delayed plating in survival slightly below the control value

  3. Evaluation of the use of automatic exposure control and automatic tube potential selection in low-dose cerebrospinal fluid shunt head CT

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, Adam N.; Bagade, Swapnil; Chatterjee, Arindam; Hicks, Brandon; McKinstry, Robert C. [Barnes Jewish Hospital, Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Washington University School of Medicine, St. Louis, MO (United States); Vyhmeister, Ross [Washington University School of Medicine, St. Louis, MO (United States); Ramirez-Giraldo, Juan Carlos [Siemens Healthcare, Malvern, PA (United States)

    2015-03-17

    Cerebrospinal fluid shunts are primarily used for the treatment of hydrocephalus. Shunt complications may necessitate multiple non-contrast head CT scans resulting in potentially high levels of radiation dose starting at an early age. A new head CT protocol using automatic exposure control and automated tube potential selection has been implemented at our institution to reduce radiation exposure. The purpose of this study was to evaluate the reduction in radiation dose achieved by this protocol compared with a protocol with fixed parameters. A retrospective sample of 60 non-contrast head CT scans assessing for cerebrospinal fluid shunt malfunction was identified, 30 of which were performed with each protocol. The radiation doses of the two protocols were compared using the volume CT dose index and dose length product. The diagnostic acceptability and quality of each scan were evaluated by three independent readers. The new protocol lowered the average volume CT dose index from 15.2 to 9.2 mGy representing a 39 % reduction (P < 0.01; 95 % CI 35-44 %) and lowered the dose length product from 259.5 to 151.2 mGy/cm representing a 42 % reduction (P < 0.01; 95 % CI 34-50 %). The new protocol produced diagnostically acceptable scans with comparable image quality to the fixed parameter protocol. A pediatric shunt non-contrast head CT protocol using automatic exposure control and automated tube potential selection reduced patient radiation dose compared with a fixed parameter protocol while producing diagnostic images of comparable quality. (orig.)

  4. Evaluation of the use of automatic exposure control and automatic tube potential selection in low-dose cerebrospinal fluid shunt head CT.

    Science.gov (United States)

    Wallace, Adam N; Vyhmeister, Ross; Bagade, Swapnil; Chatterjee, Arindam; Hicks, Brandon; Ramirez-Giraldo, Juan Carlos; McKinstry, Robert C

    2015-06-01

    Cerebrospinal fluid shunts are primarily used for the treatment of hydrocephalus. Shunt complications may necessitate multiple non-contrast head CT scans resulting in potentially high levels of radiation dose starting at an early age. A new head CT protocol using automatic exposure control and automated tube potential selection has been implemented at our institution to reduce radiation exposure. The purpose of this study was to evaluate the reduction in radiation dose achieved by this protocol compared with a protocol with fixed parameters. A retrospective sample of 60 non-contrast head CT scans assessing for cerebrospinal fluid shunt malfunction was identified, 30 of which were performed with each protocol. The radiation doses of the two protocols were compared using the volume CT dose index and dose length product. The diagnostic acceptability and quality of each scan were evaluated by three independent readers. The new protocol lowered the average volume CT dose index from 15.2 to 9.2 mGy representing a 39 % reduction (P < 0.01; 95 % CI 35-44 %) and lowered the dose length product from 259.5 to 151.2 mGy/cm representing a 42 % reduction (P < 0.01; 95 % CI 34-50 %). The new protocol produced diagnostically acceptable scans with comparable image quality to the fixed parameter protocol. A pediatric shunt non-contrast head CT protocol using automatic exposure control and automated tube potential selection reduced patient radiation dose compared with a fixed parameter protocol while producing diagnostic images of comparable quality.

  5. Effect of developmental low dose PBDE 47 exposure on thyroid hormone status and serum concentrations of FSH and inhibin B in male rats

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, A.J.M.; Kuriyama, S.N.; Akkoc, Z.; Talsness, C.E.; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin

    2004-09-15

    Several persistent halogenated organic compounds such as PCBs, dioxins and more recently, polybrominated diphenyl ethers (PBDEs) have been shown to disrupt thyroid hormone homeostasis in experimental animals. Particular concern exists regarding exposure to these compounds during critical periods of development when thyroid hormones orchestrate the growth and differentiation of many organs including the brain and the testis. While the contamination levels of PCBs and other persistent organic pollutants have declined in the past years, increasing levels of PBDEs have been detected in environmental and human samples including human breast milk. PBDEs are produced in large quantities and used worldwide as flame retardants in electrical appliances, carpets and furniture upholstery. Similar to other halogenated environmental organic pollutants, PBDEs seem to present a wide range of toxic effects including reproductive, endocrine, neurobehavioral and hepatic toxicity. Recently, it has been demonstrated that in utero and pubertal exposures to DE-71 (a commercial mixture containing mostly tetra- and penta-bromodiphenyl ethers) significantly reduce thyroxine levels (T4) in rats. The present study has focused on the possible effects of the tetra- BDE congener 2,2'4,4'-tetrabromo diphenyl ether (PBDE 47) on thyroid hormone status and associated changes on FSH and inhibin B levels in the developing male rat. We administered a single dose to gravid dams on gestation day 6 of either 140 {mu}g/kg BW or 700 {mu}g/kg BW PBDE 47. These doses are pertinent to human exposure situation because a study by She et al.3 found a mean level of 33.3 {mu}g PBDE 47 /kg fat in human breast adipose tissue with a range from 7.01 to 196 {mu}g PBDE 47 /kg fat.

  6. Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats

    Energy Technology Data Exchange (ETDEWEB)

    Stanko, Jason [National Institute of Environmental Health Sciences (NIEHS); Enoch, Rolondo [North Carolina Central University, Durham; Rayner, Jennifer L [ORNL; Davis, Christine [U.S. Environmental Protection Agency; Wolf, Douglas [U.S. Environmental Protection Agency; Malarkey, David [University of North Carolina, Chapel Hill; Fenton, Suzanne [National Institute of Environmental Health Sciences (NIEHS)

    2010-12-01

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73 mg AMM/kg body weight (BW), vehicle, or 100 mg ATR/kg BW positive control, on gestation days 15 19. Preputial separation was significantly delayed in 0.87 mg and 8.73 mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.

  7. Altered Gene Expression by Low-Dose Arsenic Exposure in Humans and Cultured Cardiomyocytes: Assessment by Real-Time PCR Arrays

    Directory of Open Access Journals (Sweden)

    Judy Mumford

    2011-06-01

    Full Text Available Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA. We found that expression of tumor necrosis factor-α (TNF-α, which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-mM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes.

  8. Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S.

    Science.gov (United States)

    Fic, A; Mlakar, S Jurković; Juvan, P; Mlakar, V; Marc, J; Dolenc, M Sollner; Broberg, K; Mašič, L Peterlin

    2015-08-01

    The bisphenols AF (BPAF) and S (BPS) are structural analogs of the endocrine disruptor bisphenol A (BPA), and are used in common products as a replacement for BPA. To elucidate genome-wide gene expression responses, estrogen-dependent osteosarcoma cells were cultured with 10 nM BPA, BPAF, or BPS, for 8 h and 3 months. Genome-wide gene expression was analyzed using the Illumina Expression BeadChip. Three months exposure had significant effects on gene expression, particularly for BPS, followed by BPAF and BPA, according to the number of differentially expressed genes (1980, 778, 60, respectively), the magnitude of changes in gene expression, and the number of enriched biological processes (800, 415, 33, respectively) and pathways (77, 52, 6, respectively). 'Embryonic skeletal system development' was the most enriched bone-related process, which was affected only by BPAF and BPS. Interestingly, all three bisphenols showed highest down-regulation of genes related to the cardiovascular system (e.g., NPPB, NPR3, TXNIP). BPA only and BPA/BPAF/BPS also affected genes related to the immune system and fetal development, respectively. For BPAF and BPS, the 'isoprenoid biosynthetic process' was enriched (up-regulated genes: HMGCS1, PDSS1, ACAT2, RCE1, DHDDS). Compared to BPA, BPAF and BPS had more effects on gene expression after long-term exposure. These findings stress the need for careful toxicological characterization of BPA analogs in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Effects of chronic low-dose radiation exposure and non-radiation factors on eye pathology in the Techa River Cohort

    International Nuclear Information System (INIS)

    Mikryukova, L.D.; Akleyev, A.V.

    2008-01-01

    Full text: As a result of the Mayak PA activities, radioactive wastes were discharged into the Techa River over the period 1949-1956. Data on eye pathology among Techa riverside residents chronically exposed to radiation (external and internal) have been collected and analyzed. The cohort which includes persons of the two genders born before 1950 gives one of the rare opportunities to assess the risk of late effects on human health associated with small-dose radiation exposure. Currently, the cohort numbers 29,749 individuals. In terms of ethnicity, 80 % of the cohort members are Slavs, and 20 % are Tartars and Bashkirs. The first study and analyses of eye pathology were conducted for this cohort during the period from 2001 through 2004. It was established that the cumulative rate of eye disease incidence increased with age and exposure dose. The relative risk value for development of ophthalmopathy among members of the study group was estimated taking into account the potential effects of gender, ethnicity and attained age. The relative risk value was 2.42 per 1 Gy of absorbed dose to soft tissues (95 % CI: 1.94; 3.03). With increase in attained age by 10 years an 8 % increase in the incidence of eye pathology was registered (p<0.001). The rate of eye disease incidence estimated for women was significantly higher than that for men (p<0.05 %). No significant differences were noted in the coefficient of eye disease incidence calculated for different ethnic groups. The structure of ophthalmopathy registered in residents of the Techa riverside villages chronically exposed in the dose range from 0 to 1,180 mGy is characterized by prevalence of cataracts, retinal and chorioid disorders. The rates of eye disease incidence were found to be dependent on external exposure dose; the highest doses were observed in the dose groups with doses 25 mGy. A statistically significant increase in the incidence of retinal angiosklerosis and a manifest tendency to develop cataracts was

  10. In utero and lactational exposure to low-dose genistein-vinclozolin mixture affects the development and growth factor mRNA expression of the submandibular salivary gland in immature female rats.

    Science.gov (United States)

    Kouidhi, Wided; Desmetz, Catherine; Nahdi, Afef; Bergès, Raymond; Cravedi, Jean-Pierre; Auger, Jacques; El May, Michèle; Canivenc-Lavier, Marie Chantal

    2012-06-01

    It has been suggested that hormonally controlled submandibular salivary gland (SSG) development and secretions may be affected by endocrine disruptor compounds. We investigated the effects of oral gestation-lactation exposure to 1 mg/kg body weight daily dose of the estrogenic soy-isoflavone genistein and/or the anti-androgenic food contaminant vinclozolin in female rats. The SSGs of female offspring were collected at postnatal day 35 to study gland morphogenesis and mRNA expression of sex-hormone receptors and endocrine growth factors as sex-dependent biomarkers. Because of high expression in neonatal SSG, mRNA expression of transforming growth factor α was also studied. Exposure to genistein, vinclozolin, or a genistein+vinclozolin mixture resulted in significantly lower numbers of striated ducts linked to an increase in their area and lower acinar proliferation (Ki-67-positive nuclei). Exposure to the mixture had the highest significant effects, which were particularly associated with repression of epidermal growth factor, nerve growth factor, and transforming growth factor α expression. In conclusion, early exposure to low doses of genistein and vinclozolin can affect glandular structure and endocrine gene mRNA expression in prepubertal SSG in female rats, and the effects are potentialized by the genistein+vinclozolin mixture. Our study provides the first evidence that SSG are targeted by both estrogenic and anti-androgenic disrupting compounds and are more sensitive to mixtures.

  11. Health effects of low dose exposure to fission products from Chernobyl and the Fermi nuclear reactor in the population of the Detroit metropolitan area

    Energy Technology Data Exchange (ETDEWEB)

    Sternglass, E.J. [Dept. of Radiology, Pittsburgh Univ. School of Medicine, PA (United States); Mangano, J.J.; Gould, J.M. [Radiation and Public Health Project, New York, NY (United States)

    2001-07-01

    The present paper describes the results of the exposure of a very large population in the Detroit, Michigan, area to fallout from Chernobyl measured in 1986, followed by the reported releases from the start-up of the Fermi-II nuclear plant in 1988 located 20 miles from the city that receives its drinking water from Lake St. Clair downwind to the north-east of the plant. Due to the prior existence of a local cancer registry for a total population of about 4 million, and the availability of reliable public-heath statistics by age, race and sex, combined with the absence of an accident known to produce population movement and stress, highly significant rises and declines of the incidence of early childhood leukemia and other cancers could be related both geographically and temporally to the observed rises and declines of fission products in the milk as well as releases from the reactor. Furthermore, surprisingly rapid rises in the incidence of breast cancer also took place in Monroe County where the reactor is located and in Macomb County downwind on Lake St. Clair to the northeast, presumably due to weakening of the immune defenses by the mix of fission products not seen so rapidly after exposure in the case of external X-rays or gamma rays. For Michigan as a whole, for which incidence of thyroid cancer at all ages combined became available after 1985, rapid rises were observed after Chernobyl and the start of the Fermi plant, using as rapidly as in the case of Belarus and Connecticut. Additionally, highly significant synchronous rises in low birth weight, infant mortality, fetal deaths, asthma and infectious disease mortality were also observed consistent with the known action of bone-seeking fission products on the immune system, following reported nuclear tests, nuclear accidents and the start-up of the Fermi plant. (orig.)

  12. Health effects of low dose exposure to fission products from Chernobyl and the Fermi nuclear reactor in the population of the Detroit metropolitan area

    International Nuclear Information System (INIS)

    Sternglass, E.J.; Mangano, J.J.; Gould, J.M.

    2001-01-01

    The present paper describes the results of the exposure of a very large population in the Detroit, Michigan, area to fallout from Chernobyl measured in 1986, followed by the reported releases from the start-up of the Fermi-II nuclear plant in 1988 located 20 miles from the city that receives its drinking water from Lake St. Clair downwind to the north-east of the plant. Due to the prior existence of a local cancer registry for a total population of about 4 million, and the availability of reliable public-heath statistics by age, race and sex, combined with the absence of an accident known to produce population movement and stress, highly significant rises and declines of the incidence of early childhood leukemia and other cancers could be related both geographically and temporally to the observed rises and declines of fission products in the milk as well as releases from the reactor. Furthermore, surprisingly rapid rises in the incidence of breast cancer also took place in Monroe County where the reactor is located and in Macomb County downwind on Lake St. Clair to the northeast, presumably due to weakening of the immune defenses by the mix of fission products not seen so rapidly after exposure in the case of external X-rays or gamma rays. For Michigan as a whole, for which incidence of thyroid cancer at all ages combined became available after 1985, rapid rises were observed after Chernobyl and the start of the Fermi plant, using as rapidly as in the case of Belarus and Connecticut. Additionally, highly significant synchronous rises in low birth weight, infant mortality, fetal deaths, asthma and infectious disease mortality were also observed consistent with the known action of bone-seeking fission products on the immune system, following reported nuclear tests, nuclear accidents and the start-up of the Fermi plant. (orig.)

  13. Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses

    Science.gov (United States)

    Saal, Frederick S. vom; Timms, Barry G.; Montano, Monica M.; Palanza, Paola; Thayer, Kristina A.; Nagel, Susan C.; Dhar, Minati D.; Ganjam, V. K.; Parmigiani, Stefano; Welshons, Wade V.

    1997-01-01

    On the basis of results of studies using high doses of estrogens, exposure to estrogen during fetal life is known to inhibit prostate development. However, it is recognized in endocrinology that low concentrations of a hormone can stimulate a tissue, while high concentrations can have the opposite effect. We report here that a 50% increase in free-serum estradiol in male mouse fetuses (released by a maternal Silastic estradiol implant) induced a 40% increase in the number of developing prostatic glands during fetal life; subsequently, in adulthood, the number of prostatic androgen receptors per cell was permanently increased by 2-fold, and the prostate was enlarged by 30% (due to hyperplasia) relative to untreated males. However, as the free serum estradiol concentration in male fetuses was increased from 2- to 8-fold, adult prostate weight decreased relative to males exposed to the 50% increase in estradiol. As a model for fetal exposure to man-made estrogens, pregnant mice were fed diethylstilbestrol (DES) from gestation days 11 to 17. Relative to controls, DES doses of 0.02, 0.2, and 2.0 ng per g of body weight per day increased adult prostate weight, whereas a 200-ng-per-g dose decreased adult prostate weight in male offspring. Our findings suggest that a small increase in estrogen may modulate the action of androgen in regulating prostate differentiation, resulting in a permanent increase in prostatic androgen receptors and prostate size. For both estradiol and DES, prostate weight first increased then decreased with dose, resulting in an inverted-U dose-response relationship. PMID:9050904

  14. Effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Anon.

    2008-01-01

    Ionizing radiation of cosmic or terrestrial origin is part of the environment in which all living things have evolved since the creation of the universe. The artificial radioactivity generated by medical diagnostic and treatment techniques, some industrial activities, radioactive fallout, etc. has now been added to this natural radioactivity. This article reviews the biological effects of the low doses of ionizing radiation to which the population is thus exposed. Their carcinogenic risk cannot simply be extrapolated from what we know about high-dose exposure. (author)

  15. Intravenous and inhalation toxicokinetics of sarin stereoisomers in atropinized guinea pigs

    NARCIS (Netherlands)

    Spruit, W.E.T.; Langenberg, J.P.; Trap, H.C.; Wiel, H.J. van der; Helmich, R.B.; Helden, H.P.M. van; Benschop, H.P.

    2000-01-01

    We report the first toxicokinetic studies of (±)-sarin. The toxicokinetics of the stereoisomers of this nerve agent were studied in anesthetized, atropinized, and restrained guinea pigs after intravenous bolus administration of a dose corresponding to 0.8 LD50 and after nose-only exposure to vapor

  16. Low levels of sarin affect the EEG in marmoset monkeys: A pilot study

    NARCIS (Netherlands)

    Helden, H.H.P.M. van; Vanwersch, R.A.P.; Kuijpers, W.C.; Trap, H.C.; Philippens, I.H.C.; Benschop, H.P.

    2004-01-01

    The main purpose of this pilot study was to estimate the lowest observable adverse effect level (LOAEL) for the electroencephalogram (EEG) upon long-term, low-level exposure of vehicle-pretreated and pyridostigmine-pretreated marmoset monkeys to sarin vapour. This is the C·t value (t = 5 h) of

  17. Cancer incidence among a cohort of subjects exposed to low-dose rate chronic radiation exposure in utero and after birth in the techa riverbank villages

    International Nuclear Information System (INIS)

    Ostroumova, E.V.; Akleyev, A.V.; Akleyev, A.V.; Hall, P.

    2003-01-01

    As a result of releases of liquid radioactive waste by the Mayak Production Association (PA) into the Techa River since 1949 till 1956 the population of the Riverside villages was exposed to a protracted effect of combined (external and internal) radiation. The 1-st-generation offspring of exposed residents born on 01.01.1950 and later were exposed both in utero and after birth. In all, 46 cancer cases, including 4 cases of leukemia, were registered among the study cohort members numbering 7,890 subjects born in the Techa Riverside villages in the Chelyabinsk province over the period since 1950 till 1998. No significant differences were noted in cancer incidence rates between men and women. Cancer incidence in the offspring's cohort was by 30-35% higher compared with the unexposed population of the USSR and Russia, the differences, however, are statistically insignificant. No influence of the parents total gonadal dose on cancer development in offspring was observed. The positive dose-effect dependence of cancer incidence on both antenatal and postnatal exposure was traced

  18. Low-dose neutron dose response of zebrafish embryos obtained from the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility

    International Nuclear Information System (INIS)

    Ng, C.Y.P.; Kong, E.Y.; Konishi, T.; Kobayashi, A.; Suya, N.; Cheng, S.H.; Yu, K.N.

    2015-01-01

    The dose response of embryos of the zebrafish, Danio rerio, irradiated at 5 h post fertilization (hpf) by 2-MeV neutrons with ≤100 mGy was determined. The neutron irradiations were made at the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility in the National Institute of Radiological Sciences (NIRS), Chiba, Japan. A total of 10 neutron doses ranging from 0.6 to 100 mGy were employed (with a gamma-ray contribution of 14% to the total dose), and the biological effects were studied through quantification of apoptosis at 25 hpf. The responses for neutron doses of 10, 20, 25, and 50 mGy approximately fitted on a straight line, while those for neutron doses of 0.6, 1 and 2.5 mGy exhibited neutron hormetic effects. As such, hormetic responses were generically developed by different kinds of ionizing radiations with different linear energy transfer (LET) values. The responses for neutron doses of 70 and 100 mGy were significantly below the lower 95% confidence band of the best-fit line, which strongly suggested the presence of gamma-ray hormesis. - Highlights: • Neutron dose response was determined for embryos of the zebrafish, Danio rerio. • Neutron doses of 0.6, 1 and 2.5 mGy led to neutron hormetic effects. • Neutron doses of 70 and 100 mGy accompanied by gamma rays led to gamma-ray hormesis

  19. Biologically based analysis of lung cancer incidence in a large Canadian occupational cohort with low-LET low-dose radiation exposure, and comparison with Japanese atomic bomb survivors

    International Nuclear Information System (INIS)

    Hazelton, W.D.; Curtis, S.B.; Moolgavkar, S.H.; Hutchinson, F.; Krewski, D.

    2003-01-01

    Lung cancer incidence is analyzed in a large Canadian National Dose Registry (CNDR) cohort with individual annual dosimetry for low-dose occupational exposure to gamma and tritium radiation using several types of multistage models. The primary analysis utilizes the two-stage clonal expansion model (TSCE), with sensitivity analyses using extensions of this model incorporating additional stages. Characteristic and distinct temporal patterns of risk are found for dose-response affecting early, middle, or late stages of carcinogenesis, e.g. initiation with one or more stages, clonal expansion, or malignant conversion. Fixed lag or lag distributions are used to model time from first malignant cell to incidence. Background rates are analyzed by gender, job classification and birth cohort. Lacking individual smoking data, surrogate doses based on US annual per capita cigarette consumption appear to account for much of the birth cohort effect. Males, with mean cumulative exposure for gamma and tritium of 11.5 mSv and 322 incident lung cancer cases have a significant dose-response with 33 cases attributable to radiation. Female dose-response, with mean cumulative exposure of 1.7 mSv and 78 incident cases, appears similar but is not statistically significant. Findings for males include an inverse-dose-rate effect (increased risk with protraction of a given dose) and dose-response effects on initiation, promotion and malignant conversion, although the effect on initiation is not statistically significant. The excess relative risk (ERR) and excess absolute risk (EAR) depend on age at exposure, duration, dose, and age at follow-up. The ERR increases with dose, tapering off at higher doses, making a plot of ERR against dose concave-downward, similar to apparent low-dose results seen below 1 Sv for solid tumor mortality of atomic bomb survivors. The concave-downward trend of ERR and the inverse-dose-rate effect are both counter to prevailing beliefs about effects of low

  20. An innovative in vitro device providing continuous low doses of γ-rays mimicking exposure to the space environment: A dosimetric study

    Science.gov (United States)

    Pereda-Loth, V.; Franceries, X.; Afonso, A. S.; Ayala, A.; Eche, B.; Ginibrière, D.; Gauquelin-Koch, G.; Bardiès, M.; Lacoste-Collin, L.; Courtade-Saïdi, M.

    2018-02-01

    Astronauts are exposed to microgravity and chronic irradiation but experimental conditions combining these two factors are difficult to reproduce on earth. We have created an experimental device able to combine chronic irradiation and altered gravity that may be used for cell cultures or plant models in a ground based facility. Irradiation was provided by thorium nitrate powder, conditioned so as to constitute a sealed source that could be placed in an incubator. Cell plates or plant seedlings could be placed in direct contact with the source or at various distances above it. Moreover, a random positioning machine (RPM) could be positioned on the source to simulate microgravity. The activity of the source was established using the Bateman formula. The spectrum of the source, calculated according to the natural decrease of radioactivity and the gamma spectrometry, showed very good adequacy. The experimental fluence was close to the theoretical fluence evaluation, attesting its uniform distribution. A Monte Carlo model of the irradiation device was processed by GATE code. Dosimetry was performed with radiophotoluminescent dosimeters exposed for one month at different locations (x and y axes) in various cell culture conditions. Using the RPM placed on the source, we reached a mean absorbed dose of gamma rays of (0.33 ± 0.17) mSv per day. In conclusion, we have elaborated an innovative device allowing chronic radiation exposure to be combined with altered gravity. Given the limited access to the International Space Station, this device could be useful to researchers interested in the field of space biology.

  1. Are radiosensitivity data derived from natural field conditions consistent with data from controlled exposures? A case study of Chernobyl wildlife chronically exposed to low dose rates.

    Science.gov (United States)

    Garnier-Laplace, J; Geras'kin, S; Della-Vedova, C; Beaugelin-Seiller, K; Hinton, T G; Real, A; Oudalova, A

    2013-07-01

    The discrepancy between laboratory or controlled conditions ecotoxicity tests and field data on wildlife chronically exposed to ionising radiation is presented for the first time. We reviewed the available chronic radiotoxicity data acquired in contaminated fields and used a statistical methodology to support the comparison with knowledge on inter-species variation of sensitivity to controlled external γ irradiation. We focus on the Chernobyl Exclusion Zone and effects data on terrestrial wildlife reported in the literature corresponding to chronic dose rate exposure situations (from background ~100 nGy/h up to ~10 mGy/h). When needed, we reconstructed the dose rate to organisms and obtained consistent unbiased data sets necessary to establish the dose rate-effect relationship for a number of different species and endpoints. Then, we compared the range of variation of radiosensitivity of species from the Chernobyl-Exclusion Zone with the statistical distribution established for terrestrial species chronically exposed to purely gamma external irradiation (or chronic Species radioSensitivity Distribution - SSD). We found that the best estimate of the median value (HDR50) of the distribution established for field conditions at Chernobyl (about 100 μGy/h) was eight times lower than the one from controlled experiments (about 850 μGy/h), suggesting that organisms in their natural environmental were more sensitive to radiation. This first comparison highlights the lack of mechanistic understanding and the potential confusion coming from sampling strategies in the field. To confirm the apparent higher sensitive of wildlife in the Chernobyl Exclusion Zone, we call for more a robust strategy in field, with adequate design to deal with confounding factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Are radiosensitivity data derived from natural field conditions consistent with data from controlled exposures? A case study of Chernobyl wildlife chronically exposed to low dose rates

    International Nuclear Information System (INIS)

    Garnier-Laplace, J.; Geras’kin, S.; Della-Vedova, C.; Beaugelin-Seiller, K.; Hinton, T.G.; Real, A.; Oudalova, A.

    2013-01-01

    The discrepancy between laboratory or controlled conditions ecotoxicity tests and field data on wildlife chronically exposed to ionising radiation is presented for the first time. We reviewed the available chronic radiotoxicity data acquired in contaminated fields and used a statistical methodology to support the comparison with knowledge on inter-species variation of sensitivity to controlled external γ irradiation. We focus on the Chernobyl Exclusion Zone and effects data on terrestrial wildlife reported in the literature corresponding to chronic dose rate exposure situations (from background∼100 nGy/h up to ∼10 mGy/h). When needed, we reconstructed the dose rate to organisms and obtained consistent unbiased data sets necessary to establish the dose rate–effect relationship for a number of different species and endpoints. Then, we compared the range of variation of radiosensitivity of species from the Chernobyl-Exclusion Zone with the statistical distribution established for terrestrial species chronically exposed to purely gamma external irradiation (or chronic Species radioSensitivity Distribution – SSD). We found that the best estimate of the median value (HDR 50 ) of the distribution established for field conditions at Chernobyl (about 100 μGy/h) was eight times lower than the one from controlled experiments (about 850 μGy/h), suggesting that organisms in their natural environmental were more sensitive to radiation. This first comparison highlights the lack of mechanistic understanding and the potential confusion coming from sampling strategies in the field. To confirm the apparent higher sensitive of wildlife in the Chernobyl Exclusion Zone, we call for more a robust strategy in field, with adequate design to deal with confounding factors. -- Highlights: ► Discrepancy between controlled tests and Chernobyl effects data on wildlife was examined. ► We proposed a method to correct the dosimetry used for Chernobyl wildlife. ► Wildlife from the

  3. Low-dose effect on blood chromosomes

    International Nuclear Information System (INIS)

    Pohl-Rueling, J.

    1992-01-01

    Linear dose response relationships of biological effects at low doses are experimentally and theoretically disputed. Structural chromosome aberration rates at doses ranging from normal background exposures up to about 30 mGy/yr in vivo and up to 50 mGy in vitro were investigated by the author and other scientists. Results are comparable and dose effect curves reveal following shapes; within the normal burden and up to 2-10 mGy/yr in vivo rates they increase sharply to about 3-6 times the lowest values; subsequent doses either from natural, occupational or accidental exposures up to about 30 mGy/yr yield either constant aberration rates, assuming a plateau, or perhaps even a decrease. In vitro experiments show comparable results up to 50 mGy. Other biological effects seem to have similar dose dependencies. The non-linearity of low-dose effects can be explained by induction of repair enzymes at certain damage to the DNA. This hypothesis is sustained experimentally and theoretically by several papers in literature. (author). 14 refs., 5 figs

  4. Synthesis of [11C]-Sarin

    International Nuclear Information System (INIS)

    Prenant, C.; Crouzel, C.

    1990-01-01

    [ 11 C]-acetone, prepared from 11 CO 2 and methyllithium, was reduced to [ 11 C]-isopropanol. The latter reacted with methylphosphonic acid difluoride in the presence of diisopropylamine, to yield [11C]-sarin. 3.4 GBq (100 mCi) of [ 11 C]-sarin may be obtained from about 55.5 GBq (1.5 Ci) of 11 CO 2 in 40 minutes. The product purified by HPLC, is obtained with a specific radioactivity ranging from 22.2 to 33.3 GBq (600 to 900 mCi/μmol.). (author)

  5. Low doses of arsenic, via perturbing p53, promotes tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ganapathy, Suthakar, E-mail: s.ganapathy@neu.edu [Center for Drug Development, Northeastern University, Boston (United States); Li, Ping [The First Affiliated Hospital, Zhengzhou University, Zhengzhou (China); The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden); Fagman, Johan [The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden); Yu, Tianqi; Lafontant, Jean [Center for Drug Development, Northeastern University, Boston (United States); Zhang, Guojun [The First Affiliated Hospital, Zhengzhou University, Zhengzhou (China); Chen, Changyan [Center for Drug Development, Northeastern University, Boston (United States); The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden)

    2016-09-01

    In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.

  6. Low doses of arsenic, via perturbing p53, promotes tumorigenesis

    International Nuclear Information System (INIS)

    Ganapathy, Suthakar; Li, Ping; Fagman, Johan; Yu, Tianqi; Lafontant, Jean; Zhang, Guojun; Chen, Changyan

    2016-01-01

    In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.

  7. Biological responses to low dose rate gamma radiation

    International Nuclear Information System (INIS)

    Magae, Junji; Ogata, Hiromitsu

    2003-01-01

    Linear non-threshold (LNT) theory is a basic theory for radioprotection. While LNT dose not consider irradiation time or dose-rate, biological responses to radiation are complex processes dependent on irradiation time as well as total dose. Moreover, experimental and epidemiological studies that can evaluate LNT at low dose/low dose-rate are not sufficiently accumulated. Here we analyzed quantitative relationship among dose, dose-rate and irradiation time using chromosomal breakage and proliferation inhibition of human cells as indicators of biological responses. We also acquired quantitative data at low doses that can evaluate adaptability of LNT with statistically sufficient accuracy. Our results demonstrate that biological responses at low dose-rate are remarkably affected by exposure time, and they are dependent on dose-rate rather than total dose in long-term irradiation. We also found that change of biological responses at low dose was not linearly correlated to dose. These results suggest that it is necessary for us to create a new model which sufficiently includes dose-rate effect and correctly fits of actual experimental and epidemiological results to evaluate risk of radiation at low dose/low dose-rate. (author)

  8. [Risk of deterministic effects after exposure to low doses of ionizing radiation: retrospective study among health workers in view of a new publication of International Commission on Radiological Protection].

    Science.gov (United States)

    Negrone, Mario; Di Lascio, Doriana

    2016-01-01

    The new recommended equivalent (publication n. 118 of International Commission on Radiological Protection) dose limit for occupational exposure of the lens of the eye is based on prevention of radiogenic cataracts, with the underlying assumption of a nominal threshold which has been adjusted from 2,5 Gy to 0.5 Gy for acute or protracted exposure. The study aim was to determine the prevalence of ocular lens opacity among healthcare workers (radiologic technologists, physicians, physician assistants) with respect to occupational exposures to ionizing radiations. Therefore, we conducted another retrospective study to explore the relationship between occupational exposure to radiation and opacity lens increase. Healthcare data (current occupational dosimetry, occupational history) are used to investigate risk of increase of opacity lens of eye. The sample of this study consisted of 148 health-workers (64 M and 84 W) aged from 28 to 66 years coming from different hospitals of the ASL of Potenza (clinic, hospital and institute with scientific feature). On the basis of the evaluation of the dosimetric history of the workers (global and effective dose) we agreed to ascribe the group of exposed subjects in cat A (equivalent dose > 2 mSV) and the group of non exposed subjects in cat B (workers with annual absorbed level of dose near 0 mSv). The analisys was conducted using SPSS 15.0 (Statistical Package for Social Science). A trend of increased ocular lens opacity was found with increasing number for workers in highest category of exposure (cat. A, Yates' chi-squared test = 13,7 p = 0,0002); variable significantly related to opacity lens results job: nurse (Χ(2)Y = 14,3 p = 0,0002) physician (Χ(2)Y = 2.2 p = 0,1360) and radiologic technologists (Χ(2)Y = 0,1 p = 0,6691). In conclusion our provides evidence that exposure to relatively low doses of ionizing radiation may be harmful to the lens of the eye and may increase a long-term risk of cataract formation; similary

  9. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation

    International Nuclear Information System (INIS)

    Korzeneva, Inna B.; Kostuyk, Svetlana V.; Ershova, Elizaveta S.; Skorodumova, Elena N.; Zhuravleva, Veronika F.; Pankratova, Galina V.; Volkova, Irina V.; Stepanova, Elena V.; Porokhovnik, Lev N.; Veiko, Natalia N.

    2016-01-01

    Highlights: • A transcribed region of human ribosomal repeat is resistant to double-strand breaks in the environment of a raised endonuclease activity. • Hybridization-based techniques are preferable for the analysis of damaged and/or oxidized genomic fragments, rather than the qRT-PCR method. • A chronic exposure to the low-dose IR induces an elevation of the rDNA content in the human circulating cfDNA as compared to cellular DNA. • An exposure to IR entails a decrease of the level of the human circulating satellite III (1q12) as compared to cellular DNA (RsatIII index). • The RrDNA/RsatIII ratio is a potential marker of a chronic IR individual exposure. - Abstract: A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N = 88) and tritium β-radiation (N = 88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the

  10. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190 Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V. [Research Centre for Medical Genetics, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Ershova, Elizaveta S. [Research Centre for Medical Genetics, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); V. A. Negovsky Research Institute of General Reanimatology, Moscow, 107031 (Russian Federation); Skorodumova, Elena N.; Zhuravleva, Veronika F.; Pankratova, Galina V.; Volkova, Irina V.; Stepanova, Elena V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190 Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N. [Research Centre for Medical Genetics, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Veiko, Natalia N. [Research Centre for Medical Genetics, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); V. A. Negovsky Research Institute of General Reanimatology, Moscow, 107031 (Russian Federation)

    2016-09-15

    Highlights: • A transcribed region of human ribosomal repeat is resistant to double-strand breaks in the environment of a raised endonuclease activity. • Hybridization-based techniques are preferable for the analysis of damaged and/or oxidized genomic fragments, rather than the qRT-PCR method. • A chronic exposure to the low-dose IR induces an elevation of the rDNA content in the human circulating cfDNA as compared to cellular DNA. • An exposure to IR entails a decrease of the level of the human circulating satellite III (1q12) as compared to cellular DNA (RsatIII index). • The RrDNA/RsatIII ratio is a potential marker of a chronic IR individual exposure. - Abstract: A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N = 88) and tritium β-radiation (N = 88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the

  11. Low-Dose Risk, Decisions, and Risk Communication

    International Nuclear Information System (INIS)

    Flynn, James; Slovic, Paul

    2001-01-01

    To conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low dose exposures. This involves the study of existing knowledge and the evaluation of science information presented within a variety of formats, as educational information, news media stories, and alternative communication methods (personal contact, small group interaction, email and internet, etc.). Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low- dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

  12. Cancer risk of low dose/low dose rate radiation: a meta-analysis of cancer data of mammals exposed to low doses of radiation

    International Nuclear Information System (INIS)

    Ogata, Hiromitsu; Magae, Junji

    2008-01-01

    Full text: Linear No Threshold (LNT) model is a basic theory for radioprotection, but the adaptability of this hypothesis to biological responses at low doses or at low dose rates is not sufficiently investigated. Simultaneous consideration of the cumulative dose and the dose rate is necessary for evaluating the risk of long-term exposure to ionizing radiation at low dose. This study intends to examine several numerical relationships between doses and dose rates in biological responses to gamma radiation. Collected datasets on the relationship between dose and the incidence of cancer in mammals exposed to low doses of radiation were analysed using meta-regression models and modified exponential (MOE) model, which we previously published, that predicts irradiation time-dependent biological response at low dose rate ionizing radiation. Minimum doses of observable risk and effective doses with a variety of dose rates were calculated using parameters estimated by fitting meta-regression models to the data and compared them with other statistical models that find values corresponding to 'threshold limits'. By fitting a weighted regression model (fixed-effects meta-regression model) to the data on risk of all cancers, it was found that the log relative risk [log(RR)] increased as the total exposure dose increased. The intersection of this regression line with the x-axis denotes the minimum dose of observable risk. These estimated minimum doses and effective doses increased with decrease of dose rate. The goodness of fits of MOE-model depended on cancer types, but the total cancer risk is reduced when dose rates are very low. The results suggest that dose response curve for cancer risk is remarkably affected by dose rate and that dose rate effect changes as a function of dose rate. For scientific discussion on the low dose exposure risk and its uncertainty, the term 'threshold' should be statistically defined, and dose rate effects should be included in the risk

  13. Whole-body low-dose computed tomography in multiple myeloma staging: Superior diagnostic performance in the detection of bone lesions, vertebral compression fractures, rib fractures and extraskeletal findings compared to radiography with similar radiation exposure.

    Science.gov (United States)

    Lambert, Lukas; Ourednicek, Petr; Meckova, Zuzana; Gavelli, Giampaolo; Straub, Jan; Spicka, Ivan

    2017-04-01

    The primary objective of the present prospective study was to compare the diagnostic performance of conventional radiography (CR) and whole-body low-dose computed tomography (WBLDCT) with a comparable radiation dose reconstructed using hybrid iterative reconstruction technique, in terms of the detection of bone lesions, skeletal fractures, vertebral compressions and extraskeletal findings. The secondary objective was to evaluate lesion attenuation in relation to its size. A total of 74 patients underwent same-day skeletal survey by CR and WBLDCT. In CR and WBLDCT, two readers assessed the number of osteolytic lesions at each region and stage according to the International Myeloma Working Group (IMWG) criteria. A single reader additionally assessed extraskeletal findings and their significance, the number of vertebral compressions and bone fractures. The radiation exposure was 2.7±0.9 mSv for WBLDCT and 2.5±0.9 mSv for CR (P=0.054). CR detected bone involvement in 127 out of 486 regions (26%; Prib fractures compared with CR (188 vs. 47; Pfractures, vertebral compressions and extraskeletal findings, which results in up- or downstaging in 24% patients according to the IMWG criteria. The attenuation of osteolytic lesions can be measured with the avoidance of the partial volume effect.

  14. Analysis of the Effect of Chronic and Low-Dose Radiation Exposure on Spermatogenic Cells of Male Large Japanese Field Mice ( Apodemus speciosus ) after the Fukushima Daiichi Nuclear Power Plant Accident.

    Science.gov (United States)

    Takino, Sachio; Yamashiro, Hideaki; Sugano, Yukou; Fujishima, Yohei; Nakata, Akifumi; Kasai, Kosuke; Hayashi, Gohei; Urushihara, Yusuke; Suzuki, Masatoshi; Shinoda, Hisashi; Miura, Tomisato; Fukumoto, Manabu

    2017-02-01

    In this study we analyzed the effect of chronic and low-dose-rate (LDR) radiation on spermatogenic cells of large Japanese field mice ( Apodemus speciosus ) after the Fukushima Daiichi Nuclear Power Plant (FNPP) accident. In March 2014, large Japanese field mice were collected from two sites located in, and one site adjacent to, the FNPP ex-evacuation zone: Tanashio, Murohara and Akogi, respectively. Testes from these animals were analyzed histologically. External dose rate from radiocesium (combined 134 Cs and 137 Cs) in these animals at the sampling sites exhibited 21 μGy/day in Tanashio, 304-365 μGy/day in Murohara and 407-447 μGy/day in Akogi. In the Akogi group, the numbers of spermatogenic cells and proliferating cell nuclear antigen (PCNA)-positive cells per seminiferous tubule were significantly higher compared to the Tanashio and Murohara groups, respectively. TUNEL-positive apoptotic cells tended to be detected at a lower level in the Murohara and Akogi groups compared to the Tanashio group. These results suggest that enhanced spermatogenesis occurred in large Japanese field mice living in and around the FNPP ex-evacuation zone. It remains to be elucidated whether this phenomenon, attributed to chronic exposure to LDR radiation, will benefit or adversely affect large Japanese field mice.

  15. Some remarks on the significance of low doses

    International Nuclear Information System (INIS)

    Cigna, A.A.

    1989-12-01

    The criteria of the present system of individual dose limitation are considered as well as the evolution of the limiting values. The assumption of the linearity of the dose-effect relationship without any threshold is probably the best approach to adopt for recommendations in radiation protection and for accounting the doses acquired by exposure to ionizing radiation. On the other hand the present evaluation of the natural background could imply a different dose-effect relationship in the low doses region and perhaps the existence of a threshold. Therefore the extrapolations which are usually made after exposures of different groups of people to low doses cannot be considered as scientifically sound. (author)

  16. Low Dose Ionizing Radiation Modulates Immune Function

    International Nuclear Information System (INIS)

    Nelson, Gregory A.

    2016-01-01

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a 'Th2 polarized' immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in

  17. Low Dose Ionizing Radiation Modulates Immune Function

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Gregory A. [Loma Linda Univ., CA (United States)

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the

  18. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Elizaveta S; Skorodumova, Elena N; Zhuravleva, Veronika F; Pankratova, Galina V; Volkova, Irina V; Stepanova, Elena V; Porokhovnik, Lev N; Veiko, Natalia N

    A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N=88) and tritium β-radiation (N=88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the circulating cfDNA as compared with the cfDNA of non-exposed people (N=109). Such index that simultaneously displays both the increase of rDNA content and decrease of satellite III content in the cfDNA (RrDNA/RsatIII) can be recommended as a marker of chronic processes in the body that involve the elevated cell death rate and/or increased blood plasma endonuclease activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Synthesis of specific labelled [methyl-14C]sarin

    International Nuclear Information System (INIS)

    Sin-Ren, A.C.; Riggio, G.; Hopff, W.H.; Waser, P.G.

    1988-01-01

    The synthesis of [methyl- 14 C]sarin ([ 14 C]methylphosphono-fluoridic acid 1-methylethyl ester) was accomplished by another approach as for nonlabelled sarin in a tele-conducted reaction vessel. The purity was estimated by IR, GC, and GC-MS and the stability in different media was examined. (author)

  20. Health hazards of low doses of ionizing radiations. Vo. 1

    International Nuclear Information System (INIS)

    El-Naggar, M.A.

    1996-01-01

    Exposure to high doses of ionizing radiation results in clinical manifestations of several disease entities that may be fatal. The onset and severity of these acute radiation syndromes are deterministic in relation to dose magnitude. Exposure to ionizing radiations at low doses and low dose rates could initiate certain damage in critical molecules of the cell, that may develop in time into serious health effects. The incidence of such delayed effects in low, and is only detectable through sophisticated epidemiological models carried out on large populations. The radiation damage induced in critical molecules of cells may develop by stochastic biochemical mechanisms of repair, residual damage, adaptive response, cellular transformation, promotion and progression into delayed health effects, the most important of which is carcinogenesis. The dose response relationship of probabilistic stochastic delayed effects of radiation at low doses and low dose rates, is very complex indeed. The purpose of this review is to provide a comprehensive understanding of the underlying mechanisms, the factors involved, and the uncertainties encountered. Contrary to acute deterministic effects, the occurrence of probabilistic delayed effects of radiation remains to be enigmatic. 7 figs

  1. Second International MELODI Workshop on Low Dose Risk Research - Slides of the presentations

    International Nuclear Information System (INIS)

    Repussard, J.; Weiss, W.; Quintana Trias, O.; Rosario Perez, M. del; Andersen, M.; Rudiger Trott, K.; Ottolenghi, A.; Smyth, V.; Graw, J.; Little, M.P.; Yonai, S.; Barcellos-Hoff, M.H.; Bouffler, S.; Chevillard, S.; Jeggo, P.; Sabatier, L.; Baatout, S.; Niwa, O.; Oesch, F.; Atkinson, M.; Averbeck, D.; Lloyd, D.; O'Neill, P.

    2011-01-01

    The MELODI (Multidisciplinary European Low Dose Initiative) mission is to impulse low dose risk research in Europe through a strategic research agenda (SRA) and road-map of priorities. The last presentation is dedicated to the SRA and its preference research programs. The other presentations deal principally with the low-dose exposure in medical uses of ionizing radiations, radiosensitivity, radiation-induced cataracts, or epidemiology and radiobiology of cardiovascular disease. This document is composed of the slides of the presentations

  2. Effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Masse, R.

    2006-01-01

    Several groups of human have been irradiated by accidental or medical exposure, if no gene defect has been associated to these exposures, some radioinduced cancers interesting several organs are observed among persons exposed over 100 to 200 mSv delivered at high dose rate. Numerous steps are now identified between the initial energy deposit in tissue and the aberrations of cell that lead to tumors but the sequence of events and the specific character of some of them are the subject of controversy. The stake of this controversy is the risk assessment. From the hypothesis called linear relationship without threshold is developed an approach that leads to predict cancers at any tiny dose without real scientific foundation. The nature and the intensity of biological effects depend on the quantity of energy absorbed in tissue and the modality of its distribution in space and time. The probability to reach a target (a gene) associated to the cancerating of tissue is directly proportional to the dose without any other threshold than the quantity of energy necessary to the effect, its probability of effect can be a more complex function and depends on the quality of the damage produced as well as the ability of the cell to repair the damage. These two parameters are influenced by the concentration of initial injuries in the target so by the quality of radiation and by the dose rate. The mechanisms of defence explain the low efficiency of radiation as carcinogen and then the linearity of effects in the area of low doses is certainly the least defensible scientific hypothesis for the prediction of the risks. (N.C.)

  3. Low-dose thioperamide injected into the cerebellar vermis of mice immediately after exposure to the elevated plus-maze impairs their avoidance behavior on re-exposure to the apparatus

    Directory of Open Access Journals (Sweden)

    J. Costa Neto

    2013-11-01

    Full Text Available The present study investigated the effect of thioperamide (THIO, an H3 histaminergic receptor antagonist, microinjected into the cerebellar vermis on emotional memory consolidation in male Swiss albino mice re-exposed to the elevated plus-maze (EPM. We implanted a guide cannula into the cerebellar vermis using stereotactic surgery. On the third day after surgery, we performed behavioral tests for two consecutive days. On the first day (exposure, the mice (n=10/group were exposed to the EPM and received THIO (0.06, 0.3, or 1.5 ng/0.1 µL immediately after the end of the session. Twenty-four hours later, the mice were re-exposed to the EPM under the same experimental conditions, but without drug injection. A reduction in the exploration of the open arms upon re-exposure to the EPM (percentage of number of entries and time spent in open arms compared with the initial exposure was used as an indicator of learning and memory. One-way analysis of variance (ANOVA followed by the Duncan post hoc test was used to analyze the data. Upon re-exposure, exploratory activity in the open arms was reduced in the control group, and with the two highest THIO doses: 0.3 and 1.5 ng/0.1 µL. No reduction was seen with the lowest THIO dose (0.06 ng/0.1 µL, indicating inhibition of the consolidation of emotional memory. None of the doses interfered with the animals' locomotor activity. We conclude that THIO at the lowest dose (0.06 ng/0.1 µL microinjected into the cerebellum impaired emotional memory consolidation in mice.

  4. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Engelward, Bevin P. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2009-09-16

    The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy

  5. A Paradigm Shift in Low Dose Radiation Biology

    Directory of Open Access Journals (Sweden)

    Z. Alatas

    2015-08-01

    Full Text Available When ionizing radiation traverses biological material, some energy depositions occur and ionize directly deoxyribonucleic acid (DNA molecules, the critical target. A classical paradigm in radiobiology is that the deposition of energy in the cell nucleus and the resulting damage to DNA are responsible for the detrimental biological effects of radiation. It is presumed that no radiation effect would be expected in cells that receive no direct radiation exposure through nucleus. The risks of exposure to low dose ionizing radiation are estimated by extrapolating from data obtained after exposure to high dose radiation. However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose radiation than they do to high dose radiation. Moreover, recent experimental evidences from many laboratories reveal the fact that radiation effects also occur in cells that were not exposed to radiation and in the progeny of irradiated cells at delayed times after radiation exposure where cells do not encounter direct DNA damage. Recently, the classical paradigm in radiobiology has been shifted from the nucleus, specifically the DNA, as the principal target for the biological effects of radiation to cells. The universality of target theory has been challenged by phenomena of radiation-induced genomic instability, bystander effect and adaptive response. The new radiation biology paradigm would cover both targeted and non-targeted effects of ionizing radiation. The mechanisms underlying these responses involve biochemical/molecular signals that respond to targeted and non-targeted events. These results brought in understanding that the biological response to low dose radiation at tissue or organism level is a complex process of integrated response of cellular targets as well as extra-cellular factors. Biological understanding of

  6. Low-dose effects hypothesis and observations on NPP personal

    Energy Technology Data Exchange (ETDEWEB)

    Georgieva, R.; Acheva, A.; Boteva, R.; Chobanova, N.; Djounova, J.; Gyuleva, I.; Ivanova, K.; Kurchatova, G.; Milchev, A.; Negoicheva, K.; Nikolov, V.; Panova, D.; Pejankov, I.; Rupova, I.; Stankova, K.; Zacharieva, E. [Radiobiology Department, National Centre of Radiobiology and Radiation Protection, Sofia (Bulgaria)

    2013-07-01

    In the modern world the use of various sources of ionizing radiation is nearly ubiquitous. They have numerous applications in industry, medicine, science, agriculture, etc. Radiation doses to workers nevertheless are commensurable to the natural background exposure. Published data on the health effects of occupational radiation exposure are often contradictory. Addressing the issue of „negative” (bystander effects, genomic instability) and „positive” (adaptive response, radiation hormesis) effects of low doses is important and has a significant social and economic impact. In this paper we summarize the results of our extensive monitoring of nuclear power plant (NPP) staff. We believe it is a cohort suitable for analysis of health effects at low doses, because of their good medical and dosimetric control. Our results rather support the idea of absence of adverse health effects in NPP workers. (author)

  7. Reduced oxygen enhancement ratio at low doses

    International Nuclear Information System (INIS)

    Palcic, B.; Skarsgard, L.D.

    1984-01-01

    The oxygen depletion rate in cell suspensions was measured using a Clark electrode. It was found that under experimental conditions used in this laboratory for hypoxic irradiations, the oxygen levels before the start of irradiation are always below 0.1μm, the levels which could give any significant enhancement to radiation inactivation by x-rays. The measured O/sub 2/ depletion rates were comparable to those reported in the literature. Chinese hamster cells (CHO) were made hypoxic by gas exchange, combined with metabolic consumption of oxygen by cells at 37 0 C. Full survival curves were determined in the dose range 0 to 3Gy using the low dose survival assay. The results confirmed the authors' earlier finding that the OER decreases at low doses. The authors therefore believe that the dose-dependent OER is a true radiobiological phenomenon and not an artifact of the experimental method used in the low dose survival assay

  8. Pseudo LRM waveforms from CryoSat SARin acquisition

    Science.gov (United States)

    Scagliola, Michele; Fornari, Marco; Bouffard, Jerome; Parrinello, Tommaso; Féménias, Pierre

    2016-04-01

    CryoSat was launched on the 8th April 2010 and is the first European ice mission dedicated to the monitoring of precise changes in the thickness of polar ice sheets and floating sea ice. The main payload of CryoSat is a Ku-band pulsewidth limited radar altimeter, called SIRAL (Synthetic interferometric radar altimeter). When commanded in SARIn (synthetic aperture radar interferometry) mode, through coherent along-track processing of the returns received from two antennas, the interferometric phase related to the first arrival of the echo is used to retrieve the angle of arrival of the scattering in the across-track direction. When SIRAL operates in SAR or SARin mode, the obtained waveforms have an along-track resolution and a speckle reduction which is increased with respect to the pulse-limited waveforms. Anyway, in order to analyze the continuity of the geophysical retrieved parameters among different acquisition modes, techniques to transform SARin mode data to pseudo-LRM mode data are welcome. The transformation process is known as SAR reduction and it is worth recalling here that only approximate pseudo-LRM waveforms can be obtained in case of closed burst acquisitions, as SIRAL operates. A SAR reduction processing scheme has been developed to obtain pseudo-LRM waveforms from CryoSat SARin acquisition. As a trade-off between the along-track length on Earth surface contributing to one SARin pseudo-LRM waveform and the noisiness of the waveform itself, it has been chosen a SAR reduction approach based on the averaging of all the SARin echoes received each 20Hz, resulting in one pseudo-LRM waveform for each SARin burst given the SARin burst repetition period. SARin pseudo-LRM waveforms have been produced for CryoSat acquisition both on ice and sea surfaces, aiming at verifying the continuity of the retracked surface height over the ellipsoid between genuine LRM products and pseudo-LRM products. Moreover, the retracked height from the SARin pseudo-LRM has been

  9. Rapid biosynthesis of silver nanoparticles using Crotalaria verrucosa leaves against the dengue vector Aedes aegypti: what happens around? An analysis of dragonfly predatory behaviour after exposure at ultra-low doses.

    Science.gov (United States)

    Murugan, Kadarkarai; Sanoopa, C P; Madhiyazhagan, Pari; Dinesh, Devakumar; Subramaniam, Jayapal; Panneerselvam, Chellasamy; Roni, Mathath; Suresh, Udaiyan; Nicoletti, Marcello; Alarfaj, Abdullah A; Munusamy, Murugan A; Higuchi, Akon; Kumar, Suresh; Perumalsamy, Haribalan; Ahn, Young-Joon; Benelli, Giovanni

    2016-01-01

    Aedes aegypti is a primary vector of dengue, a mosquito-borne viral disease infecting 50-100 million people every year. Here, we biosynthesised mosquitocidal silver nanoparticles (AgNP) using the aqueous leaf extract of Crotalaria verrucosa. The green synthesis of AgNP was studied by UV-vis spectroscopy, SEM, EDX and FTIR. C. verrucosa-synthesised AgNPs were toxic against A. aegypti larvae and pupae. LC50 of AgNP ranged from 3.496 ppm (I instar larvae) to 17.700 ppm (pupae). Furthermore, we evaluated the predatory efficiency of dragonfly nymphs, Brachydiplax sobrina, against II and III instar larvae of A. aegypti in an aquatic environment contaminated with ultra-low doses of AgNP. Under standard laboratory conditions, predation after 24 h was 87.5% (II) and 54.7% (III). In an AgNP-contaminated environment, predation was 91 and 75.5%, respectively. Overall, C. verrucosa-synthesised AgNP could be employed at ultra-low doses to reduce larval population of dengue vectors enhancing predation rates of dragonfly nymphs.

  10. Aum Shinrikyo's Chemical and Biological Weapons: More Than Sarin.

    Science.gov (United States)

    Tu, A T

    2014-07-01

    The radical religious group Aum Shinrikyo was founded in Japan in the 1980s and grew rapidly in the 1990s. Aum members perpetrated a mass murder in Matsumoto City in 1994, where they used sarin as a chemical weapon to poison approximately 500 civilians. On March 20, 1995, Aum deployed sarin in an even larger terrorist attack on the Tokyo Subway System, which poisoned some 6,000 people. After the Tokyo Subway attack, the Japanese Police arrested the sect's senior members. From 2005 through 2011, 13 of these senior members were sentenced to death. In this article, aspects of Aum's chemical and biological terrorism are reviewed. Sarin production efforts by the sect are described, including how the degradation product of sarin in soil, methylphosphonic acid, enabled the detection of sarin production sites. Also, Aum's chemical-warfare agents other than sarin are described, as are its biological weapons. The author was permitted by the Japanese government to interview Dr. Tomomasa Nakagawa, one of the senior members of Aum Shinrikyo. From Dr. Nakagawa the author obtained valuable inside information about Aum's chemical and biological weapons programs. Copyright © 2014 Central Police University.

  11. Systemic effects of low-dose dopamine during administration of cytarabine.

    Science.gov (United States)

    Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

    2017-09-01

    Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

  12. Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery

    Science.gov (United States)

    A low dose of radioactive iodine given after surgery for thyroid cancer destroyed (ablated) residual thyroid tissue as effectively as a higher dose, with fewer side effects and less exposure to radiation, according to two randomized controlled trials.

  13. Biological influence from low dose and low-dose rate radiation

    International Nuclear Information System (INIS)

    Magae, Junji

    2007-01-01

    Although living organisms have defense mechanisms for radioadaptive response, the influence is considered to vary qualitatively and quantitatively for low dose and high dose, as well as for low-dose rate and high-dose rate. This article describes the bioresponse to low dose and low-dose rate. Among various biomolecules, DNA is the most sensitive to radiation, and accurate replication of DNA is an essential requirement for the survival of living organisms. Also, the influence of active enzymes resulted from the effect of radiation on enzymes in the body is larger than the direct influence of radiation on the body. After this, the article describes the carcinogenic risk by low-dose radiation, and then so-called Hormesis effect to create cancer inhibition effect by stimulating active physiology. (S.K.)

  14. Stimulation of seeds by low dose irradiation

    International Nuclear Information System (INIS)

    Lawson, Helen

    1976-05-01

    The first section of the bibliography lists materials on the stimulation of seeds by low dose irradiation, with particular reference to stimulation of germination and yield. The second section contains a small number of selected references on seed irradiation facilities. (author)

  15. Low doses of neutrons induce changes in gene expression

    International Nuclear Information System (INIS)

    Woloschak, G.E.; Chang-Liu, C.M.; Panozzo, J.; Libertin, C.R.

    1993-01-01

    Studies were designed to identify genes induced following low-dose neutron but not following γ-ray exposure in fibroblasts. Our past work had shown differences in the expression of β-protein kinase C and c-fos genes, both being induced following γ-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not γ-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to γ rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure

  16. MELODI: The 'Multidisciplinary European Low-Dose Initiative'

    International Nuclear Information System (INIS)

    Belli, M.; Salomaa, S.; Ottolenghi, A.

    2011-01-01

    The importance of research to reduce uncertainties in risk assessment of low and protracted exposures is now recognised globally. In Europe a new initiative, called 'Multidisciplinary European Low Dose Initiative' (MELODI), has been proposed by a 'European High Level and Expert Group on low-dose risk research' (www.hleg.de), aimed at integrating national and EC (Euratom) efforts. Five national organisations: BfS (DE), CEA (FR), IRSN (FR), ISS (IT) and STUK (FI), with the support of the EC, have initiated the creation of MELODI by signing a letter of intent. In the forthcoming years, MELODI will integrate in a step-by-step approach EU institutions with significant programmes in the field and will be open to other scientific organisations and stakeholders. A key role of MELODI is to develop and maintain over time a strategic research agenda (SRA) and a road map of scientific priorities within a multidisciplinary approach, and to transfer the results for the radiation protection system. Under the coordination of STUK a network has been proposed in the 2009 Euratom Programme, called DoReMi (Low-Dose Research towards Multidisciplinary Integration), which can help the integration process within the MELODI platform. DoReMi and the First MELODI Open Workshop, organised by BfS in September 2009, are now important inputs for the European SRA. (authors)

  17. Problems linked to effects of ionizing radiations low doses

    International Nuclear Information System (INIS)

    Anon.

    1995-10-01

    The question of exposure to ionizing radiations low doses and risks existing for professional and populations has been asked again, with the recommendations of the International Commission of Radiation Protection (ICRP) to lower the previous standards and agreed as guides to organize radiation protection, by concerned countries and big international organisms. The sciences academy presents an analysis which concerned on epidemiological and dosimetric aspects in risk estimation, on cellular and molecular aspects of response mechanism to irradiation. The observation of absence of carcinogen effects for doses inferior to 200 milli-sieverts and a re-evaluation of data coming from Nagasaki and Hiroshima, lead to revise the methodology of studies to pursue, to appreciate more exactly the effects of low doses, in taking in part, particularly, the dose rate. The progress of molecular and cellular biology showed that the extrapolation from high doses to low doses is not in accordance with actual data. The acknowledge of DNA repair and carcinogenesis should make clearer the debate. (N.C.). 61 refs., 9 annexes

  18. New risk estimates at low doses

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1992-01-01

    The age of molecular radiation epidemiology may be at hand. The techniques are available to establish with the degree of precision required to determine whether agent-specific mutations can be identified consistently. A concerted effort to examine radiation-induced changes in as many relevant genes as possible appears to be justified. Cancers in those exposed to low doses of ionizing radiation should be chosen for the investigation. Parallel studies of radiation-induced cancers in experimental animals would not only complement the human studies, but perhaps reveal approaches to extrapolation of risk estimates across species. A caveat should be added to this optimistic view of what molecular studies might contribute to the knotty problem of risk estimates at low doses. The suggestions are made by one with no expertise in the field of molecular biology

  19. Cytogenetic effects of low-dose radiation

    International Nuclear Information System (INIS)

    Metalli, P.

    1983-01-01

    The effects of ionizing radiation on chromosomes have been known for several decades and dose-effect relationships are also fairly well established in the mid- and high-dose and dose-rate range for chromosomes of mammalian cells. In the range of low doses and dose rates of different types of radiation few data are available for direct analysis of the dose-effect relationships, and extrapolation from high to low doses is still the unavoidable approach in many cases of interest for risk assessment. A review is presented of the data actually available and of the attempts that have been made to obtain possible generalizations. Attention is focused on some specific chromosomal anomalies experimentally induced by radiation (such as reciprocal translocations and aneuploidies in germinal cells) and on their relevance for the human situation. (author)

  20. Estimation of radiation risks at low dose

    International Nuclear Information System (INIS)

    1990-04-01

    The report presents a review of the effects caused by radiation in low doses, or at low dose rates. For the inheritable (or ''genetic''), as well as for the cancer producing effects of radiation, present evidence is consistent with: (a) a non-linear relationship between the frequency of at least some forms of these effects, with comparing frequencies caused by doses many times those received annually from natural sources, with those caused by lower doses; (b) a probably linear relationship, however, between dose and frequency of effects for dose rates in the region of that received from natural sources, or at several times this rate; (c) no evidence to indicate the existence of a threshold dose below which such effects are not produced, and a strong inference from the mode of action of radiation on cells at low dose rates that no such thresholds are likely to apply to the detrimental, cancer-producing or inheritable, effects resulting from unrepaired damage to single cells. 19 refs

  1. Deep learning for low-dose CT

    Science.gov (United States)

    Chen, Hu; Zhang, Yi; Zhou, Jiliu; Wang, Ge

    2017-09-01

    Given the potential risk of X-ray radiation to the patient, low-dose CT has attracted a considerable interest in the medical imaging field. Currently, the main stream low-dose CT methods include vendor-specific sinogram domain filtration and iterative reconstruction algorithms, but they need to access raw data whose formats are not transparent to most users. Due to the difficulty of modeling the statistical characteristics in the image domain, the existing methods for directly processing reconstructed images cannot eliminate image noise very well while keeping structural details. Inspired by the idea of deep learning, here we combine the autoencoder, deconvolution network, and shortcut connections into the residual encoder-decoder convolutional neural network (RED-CNN) for low-dose CT imaging. After patch-based training, the proposed RED-CNN achieves a competitive performance relative to the-state-of-art methods. Especially, our method has been favorably evaluated in terms of noise suppression and structural preservation.

  2. Low doses of gamma radiation in soybean

    International Nuclear Information System (INIS)

    Franco, José G.; Franco, Suely S.H.; Villavicencio, Anna L.C.; Arthur, Valter; Arthur, Paula B.; Franco, Caio H.

    2017-01-01

    The degree of radiosensitivity depends mostly on the species, the stage of the embryo at irradiation, the doses employed and the criteria used to measure the effect. One of the most common criteria to evaluate radiosensitivity in seeds is to measure the average plant production. Dry soya seeds were exposed to low doses of gamma radiation from source of Cobalt-60, type Gammecell-220, at 0.210 kGy dose rate. In order to study stimulation effects of radiation on germination, plant growth and production. A treatment with four radiation doses was applied as follows: 0 (control); 12.5; 25.0 and 50.0 Gy. Seed germination and harvested of number of seeds and total production were assessed to identify occurrence of stimulation. Soya seeds number and plants were handled as for usual seed production in Brazil. The low doses of gamma radiation in the seeds that stimulate the production were the doses of 12.5 and 50.0 Gy. The results show that the use of low doses of gamma radiation can stimulate germination and plant production. (author)

  3. Low doses of gamma radiation in soybean

    Energy Technology Data Exchange (ETDEWEB)

    Franco, José G.; Franco, Suely S.H.; Villavicencio, Anna L.C., E-mail: zegilmar60@gmail.com, E-mail: gilmita@uol.com.br, E-mail: villavic@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil); Arthur, Valter; Arthur, Paula B., E-mail: arthur@cena.usp.br [Centro de Energia Nuclear na Agricultura (CENA/USP), Piracicaba, SP (Brazil); Franco, Caio H. [Universidade Federal de São Paulo (UNIFESP), SP (Brazil). Departamento de Microbiologia, Imunologia e Parasitologia

    2017-07-01

    The degree of radiosensitivity depends mostly on the species, the stage of the embryo at irradiation, the doses employed and the criteria used to measure the effect. One of the most common criteria to evaluate radiosensitivity in seeds is to measure the average plant production. Dry soya seeds were exposed to low doses of gamma radiation from source of Cobalt-60, type Gammecell-220, at 0.210 kGy dose rate. In order to study stimulation effects of radiation on germination, plant growth and production. A treatment with four radiation doses was applied as follows: 0 (control); 12.5; 25.0 and 50.0 Gy. Seed germination and harvested of number of seeds and total production were assessed to identify occurrence of stimulation. Soya seeds number and plants were handled as for usual seed production in Brazil. The low doses of gamma radiation in the seeds that stimulate the production were the doses of 12.5 and 50.0 Gy. The results show that the use of low doses of gamma radiation can stimulate germination and plant production. (author)

  4. Biological effects of low doses of radiation at low dose rate

    International Nuclear Information System (INIS)

    1996-05-01

    The purpose of this report was to examine available scientific data and models relevant to the hypothesis that induction of genetic changes and cancers by low doses of ionizing radiation at low dose rate is a stochastic process with no threshold or apparent threshold. Assessment of the effects of higher doses of radiation is based on a wealth of data from both humans and other organisms. 234 refs., 26 figs., 14 tabs

  5. Harderian Gland Tumorigenesis: Low-Dose and LET Response

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Polly Y. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cucinotta, Francis A. [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Bjornstad, Kathleen A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Bakke, James [SRI International, Menlo Park, CA (United States). Biosciences Div.; Rosen, Chris J. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Du, Nicholas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Fairchild, David G. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cacao, Eliedonna [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Blakely, Eleanor A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

    2016-04-19

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  6. Low-dose radiation attenuates chemical mutagenesis in vivo. Cross adaptation

    International Nuclear Information System (INIS)

    Kakinuma, Shizuko; Yamauchi, Kazumi; Amasaki, Yoshiko; Nishimura, Mayumi; Shimada, Yoshiya

    2009-01-01

    The biological effects of low-dose radiation are not only of social concern but also of scientific interest. The radioadaptive response, which is defined as an increased radioresistance by prior exposure to low-dose radiation, has been extensively studied both in vitro and in vivo. Here we briefly review the radioadaptive response with respect to mutagenesis, survival rate, and carcinogenesis in vivo, and introduce our recent findings of cross adaptation in mouse thymic cells, that is, the suppressive effect of repeated low-dose radiation on mutation induction by the alkylating agent N-ethyl-N-nitrosourea. (author)

  7. Bioavailability of diclofenac potassium at low doses

    Science.gov (United States)

    Hinz, Burkhard; Chevts, Julia; Renner, Bertold; Wuttke, Henrike; Rau, Thomas; Schmidt, Andreas; Szelenyi, Istvan; Brune, Kay; Werner, Ulrike

    2005-01-01

    Aim Diclofenac-K has been recently launched at low oral doses in different countries for over-the-counter use. However, given the considerable first-pass metabolism of diclofenac, the degree of absorption of diclofenac-K at low doses remained to be determined. The aim of this study was to determine the bioavailability of low-dose diclofenac-K. Methods A randomized, three-way, cross-over study was performed in 10 subjects. Each received diclofenac-K, 22.5 mg via short-term i.v. infusion and orally at single doses of 12.5 mg and 25 mg. Results Mean (± SD) times to maximal plasma concentration (tmax) of diclofenac were 0.48 ± 0.28 h (12.5 mg) and 0.93 ± 0.96 h (25 mg). The absolute bioavailability of diclofenac-K after oral administration did not differ significantly in the 12.5-mg and 25-mg dose group (63.1 ± 12.6% vs. 65.1 ± 19.4%, respectively). The 90% confidence intervals for the AUC∞ and AUCt ratios for the two oral regimes were 82.6, 103.4% (point estimate 92.4%) and 86.2, 112.9% (point estimate 98.6%), respectively. These values were within the acceptance criteria for bioequivalence (80–125%). Conclusions Our data indicate that diclofenac-K is rapidly and well absorbed at low dose, and are consistent with a rapid onset of action of the drug. Abbreviations AUC, area under plasma concentraton-time curve; Cmax, peak plasma concentration; CI, confidence interval; COX, cyclooxygenase; D, dose; F, absolute bioavailability; tmax, time to reach Cmax. PMID:15606444

  8. Low dose radiation and diabetes mellitus

    International Nuclear Information System (INIS)

    Zhao Hongguang; Gong Shouliang; Cai Lu

    2006-01-01

    Induction of hormesis and adaptive response by low-dose radiatio (LDR) has been extensively indicated. It's mechanism may be related with the protective protein and antioxidants that LDR induced, which take effects on the diabetes mellitus (DM) and other diseases. This review will summarize available dat with emphasis on three points: the preventive effect of LDR on the development of diabetes, the therapeutic effect of LDR on diabetic complications and possible mechanisms by which LDR prevents the development of diabetes and diabetic complications. Finally, the perspectives of LDR clinical, diabetes-related implication are discussed. (authors)

  9. induction of cytogenetic damage by low doses of acute and chronic gamma-radiation in mammalian and plant cells

    International Nuclear Information System (INIS)

    Zaichkina, S.I.; Aptikaeva, G.F.; Akhmadieva, A.Ch.; Rozanova, O.M.; Smirnova, E.N.; Rogova, N.J.; Ganassi, E.E.

    1997-01-01

    The problem of the biological action of low doses of mutagenic agents has received much attention recently. It is shown that the risk factors for low-dose exposure are greater that it was calculated by extrapolation from higher to lower doses. The aim of the present study was to investigate the effect of low doses on various biological objects including animal and plant cells. (authors)

  10. Induction of cytogenetic damage by low doses of acute and chronic gamma-radiation in mammalian and plant cells

    Energy Technology Data Exchange (ETDEWEB)

    Zaichkina, S.I.; Aptikaeva, G.F.; Akhmadieva, A.Ch.; Rozanova, O.M.; Smirnova, E.N.; Rogova, N.J.; Ganassi, E.E. [Institute of Theoretical and Experimental Biophysics, Moscow (Russian Federation)

    1997-03-01

    The problem of the biological action of low doses of mutagenic agents has received much attention recently. It is shown that the risk factors for low-dose exposure are greater that it was calculated by extrapolation from higher to lower doses. The aim of the present study was to investigate the effect of low doses on various biological objects including animal and plant cells. (authors)

  11. Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Fujimura, Masatake, E-mail: fujimura@nimd.go.jp [Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto (Japan); Usuki, Fusako [Department of Clinical Medicine, National Institute for Minamata Disease, Kumamoto (Japan); Cheng, Jinping; Zhao, Wenchang [School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2016-05-01

    Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

  12. Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

    International Nuclear Information System (INIS)

    Fujimura, Masatake; Usuki, Fusako; Cheng, Jinping; Zhao, Wenchang

    2016-01-01

    Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

  13. Initial oxidation of TiFe{sub 1−x}Mn{sub x} (x = 0–0.3) by low dose exposures to H{sub 2}O and O{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Shwartz, A. [Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105 (Israel); Shamir, N., E-mail: noah.shamir@gmail.com [Nuclear research Center – Negev, P.O. Box 9001, Beer-Sheva 84190 (Israel); Froumin, N. [Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105 (Israel); Zalkind, S.; Edry, I.; Haim, A. [Nuclear research Center – Negev, P.O. Box 9001, Beer-Sheva 84190 (Israel); Mintz, M.H. [Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105 (Israel); Nuclear research Center – Negev, P.O. Box 9001, Beer-Sheva 84190 (Israel)

    2014-10-15

    Highlights: • Thermodynamics of adsorption and initial oxidation of TiFe{sub 1−x}Mn{sub x} by H{sub 2}O versus O{sub 2}. • Explanation of different oxide formations. • Explanation of the role of the different constituents of the alloys in the processes. - Abstract: The very initial room-temperature oxidation processes of the ternary pseudo-binary TiFe{sub 1−x}Mn{sub x} (x = 0–0.3) intermetallics by trace amounts of H{sub 2}O vapor and O{sub 2} were studied utilizing XPS and AES techniques. Different reactivities of the two gases were obtained, with a lower oxidation ability of H{sub 2}O, relative to O{sub 2}, as anticipated from thermodynamic considerations. The exposure to O{sub 2} results in a two stage oxidation of the Ti ingredient, which first converts into a divalent TiO (up to exposures of about 2 L), then proceeds into a tetravalent TiO{sub 2} form. Unlike oxygen, water exposure produces only the divalent oxide through the whole exposure range studied (11 L). The Mn component in these compounds is oxidized only by O{sub 2} and not by H{sub 2}O. The Fe ingredient is not oxidized at all and remains in its metallic form up to exposures of 30 L.

  14. Low and very low doses, new recommendations?

    International Nuclear Information System (INIS)

    Foucher, N.

    1999-01-01

    The topic of the seminar organized by the world council of nuclear workers (WONUC) was the effects of low or very low doses on human health. Discussions centred round the linearity of the relation between dose and effect in the evaluation and management of the health hazard. The recommendations proposed by ICPR (international commission for radiological protection) are based on this linearity as a precaution. On the one hand it is remembered that low dose irradiation might be beneficial. It has been proved that the irradiation of the whole body is efficient in case of Hodgkin lymphoma. On the other hand it is remembered that doses as low as 10 mSv in utero have led to an excess of cancer in children. Studies based on experimentally radio-induced cancers have been carried out in Japan, China, Canada and France.Their results seem to be not consistent with the hypothesis of linearity. During the last decade a lot of work has been made but a conclusion is far to be reached, it is said that the American department of energy (DOE) has invited bids in 1999 to launch research programs in order to clarify the situation. (A.C.)

  15. Metabolomics: new prospects in low-dose radio-toxicology

    International Nuclear Information System (INIS)

    Souidi, Maamar; Grison, Stephane

    2014-01-01

    There is recurring public concern regarding the health impact of chronic exposure to low-dose ionizing radiation. This concern is further heightened when possible sources of exposure are identified, such as disused mines, the operation of nuclear facilities and radioactive waste disposal facilities, accidental release from fuel cycle facilities or the possible return of residents to areas contaminated following a reactor accident, such as the one that occurred at Fukushima. In keeping with the guidelines set out in the European strategic research agenda for MELODI, IRSN is conducting an extensive, largely experiment-based, research program to acquire scientific data to respond to this concern. The program has already revealed that chronic ingestion of cesium-137 or uranium induces many subtle, generally slight, metabolic changes, the overall biological effects of which remain to be studied. A recent 'broad-spectrum' analytical technique known as metabolomics was used to pinpoint these metabolic changes. (authors)

  16. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kleiman, Norman Jay [Columbia University

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9

  17. Does area deprivation modify the association between exposure to a nitrate and low-dose atrazine metabolite mixture in drinking water and small for gestational age? A historic cohort study.

    Science.gov (United States)

    Limousi, F; Albouy-Llaty, M; Carles, C; Dupuis, A; Rabouan, S; Migeot, V

    2014-04-01

    Birth weight may be influenced by environmental and socio-economic factors that could interact. The main objective of our research was to investigate whether area deprivation may modify the association between drinking water exposure to a mixture of atrazine metabolites and nitrates during the second trimester of pregnancy and prevalence of small for gestational age (SGA) neonates. We conducted a historic cohort study in Deux-Sèvres, France between 2005 and 2010, using birth records, population census and regularly performed drinking water withdrawals at community water systems. Exposure to an atrazine metabolite/nitrate mixture in drinking water was divided into six classes according to the presence or absence of atrazine metabolites and to the terciles of nitrate concentrations in each trimester of pregnancy. We used a logistic regression to model the association between SGA and mixture exposure at the second trimester while taking into account the area deprivation measured by the Townsend index as an effect modifier and controlling for the usual confounders. We included 10,784 woman-neonate couples. The risk of SGA when exposed to second tercile of nitrate without atrazine metabolites was significantly greater in women living in less deprived areas (OR = 2.99; 95 % CI (1.14, 7.89)), whereas it was not significant in moderately and more deprived areas. One of the arguments used to explain this result is the presence of competing risk factors in poorer districts.

  18. Proceedings of the 8. LOWRAD: International conference on the effects of low doses and very low doses of ionizing radiation on human health and biotopes

    International Nuclear Information System (INIS)

    2009-01-01

    Theoretical and experimental papers are presented in these proceedings covering the following subjects: radiation protection, dosimetry, radiation dosimetry, cells, technetium, plutonium, uranium, thorium, low dose irradiation, radiation doses, cesium, radiation chemistry, nuclear medicine, safety and occupational exposure, neoplasm, cytology and radioisotopes

  19. Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial anthropomorphic phantoms

    NARCIS (Netherlands)

    Koivisto, J.H.; Wolff, J.E.; Kiljunen, T.; Schulze, D.; Kortesniemi, M.

    2015-01-01

    The aims of this study were to characterize reinforced metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low-dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the

  20. The risk of low doses of ionising radiation and the linear no threshold relationship debate

    International Nuclear Information System (INIS)

    Tubiana, M.; Masse, R.; Vathaire, F. de; Averbeck, D.; Aurengo, A.

    2007-01-01

    The ICRP and the B.E.I.R. VII reports recommend a linear no threshold (L.N.T.) relationship for the estimation of cancer excess risk induced by ionising radiations (IR), but the 2005 report of Medicine and Science French Academies concludes that it leads to overestimate of risk for low and very low doses. The bases of L.N.T. are challenged by recent biological and animal experimental studies which show that the defence against IR involves the cell microenvironment and the immunologic system. The defence mechanisms against low doses are different and comparatively more effective than for high doses. Cell death is predominant against low doses. DNA repairing is activated against high doses, in order to preserve tissue functions. These mechanisms provide for multicellular organisms an effective and low cost defence system. The differences between low and high doses defence mechanisms are obvious for alpha emitters which show several greys threshold effects. These differences result in an impairment of epidemiological studies which, for statistical power purpose, amalgamate high and low doses exposure data, since it would imply that cancer IR induction and defence mechanisms are similar in both cases. Low IR dose risk estimates should rely on specific epidemiological studies restricted to low dose exposures and taking precisely into account potential confounding factors. The preliminary synthesis of cohort studies for which low dose data (< 100 mSv) were available show no significant risk excess, neither for solid cancer nor for leukemias. (authors)

  1. Study on cellular survival adaptive response induced by low dose irradiation of 153Sm

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Xiao Dong

    1999-01-01

    The present study engages in determining whether low dose irradiation of 153 Sm could cut down the responsiveness of cellular survival to subsequent high dose exposure of 153 Sm so as to make an inquiry into approach the protective action of adaptive response by second irradiation of 153 Sm. Experimental results indicate that for inductive low dose of radionuclide 153 Sm 3.7 kBq/ml irradiated beforehand to cells has obvious resistant effect in succession after high dose irradiation of 153 Sm 3.7 x 10 2 kBq/ml was observed. Cells exposed to low dose irradiation of 153 Sm become adapted and therefore the subsequent cellular survival rate induced by high dose of 153 Sm is sufficiently higher than high dose of 153 Sm merely. It is evident that cellular survival adaptive response could be induced by pure low dose irradiation of 153 Sm only

  2. Molecular initiating events of the intersex phenotype: Low-dose exposure to 17α-ethinylestradiol rapidly regulates molecular networks associated with gonad differentiation in the adult fathead minnow testis

    International Nuclear Information System (INIS)

    Feswick, April; Loughery, Jennifer R.; Isaacs, Meghan A.; Munkittrick, Kelly R.; Martyniuk, Christopher J.

    2016-01-01

    Highlights: • Male fathead minnow were exposed to 17alpha ethinylestradiol (EE2). • Both 11-ketotestosterone and testosterone production was decreased relative to controls. • A gene network associated with doublesex and mab-3 related transcription factor 1 were suppressed. • Genes involved in granulosa cell development were increased and sensitive to EE2 exposure. • Molecular initiating events that may be related to the intersex condition were identified. - Abstract: Intersex, or the presence of oocytes in the testes, has been documented in fish following exposure to wastewater effluent and estrogenic compounds. However, the molecular networks underlying the intersex condition are not completely known. To address this, we exposed male fathead minnows to a low, environmentally-relevant concentration of 17alpha-ethinylestradiol (EE2) (15 ng/L) and measured the transcriptome response in the testis after 96 h to identify early molecular initiating events that may proceed the intersex condition. The short-term exposure to EE2 did not affect gonadosomatic index and proportion of gametes within the testes. However, the production of 11-ketotestosterone and testosterone from the testis in vitro was decreased relative to controls. Expression profiling using a 8 × 60 K fathead minnow microarray identified 10 transcripts that were differentially expressed in the testes, the most dramatic change being that of coagulation factor XIII A chain (20-fold increase). Transcripts that included guanine nucleotide binding protein (Beta Polypeptide 2), peroxisome proliferator-activated receptor delta, and WNK lysine deficient protein kinase 1a, were down-regulated by EE2. Subnetwork enrichment analysis revealed that EE2 suppressed transcriptional networks associated with steroid metabolism, hormone biosynthesis, and sperm mobility. Most interesting was that gene networks associated with doublesex and mab-3 related transcription factor 1 (dmrt1) were suppressed in the adult

  3. Molecular initiating events of the intersex phenotype: Low-dose exposure to 17α-ethinylestradiol rapidly regulates molecular networks associated with gonad differentiation in the adult fathead minnow testis

    Energy Technology Data Exchange (ETDEWEB)

    Feswick, April; Loughery, Jennifer R.; Isaacs, Meghan A.; Munkittrick, Kelly R.; Martyniuk, Christopher J., E-mail: cmartyni@yahoo.ca

    2016-12-15

    Highlights: • Male fathead minnow were exposed to 17alpha ethinylestradiol (EE2). • Both 11-ketotestosterone and testosterone production was decreased relative to controls. • A gene network associated with doublesex and mab-3 related transcription factor 1 were suppressed. • Genes involved in granulosa cell development were increased and sensitive to EE2 exposure. • Molecular initiating events that may be related to the intersex condition were identified. - Abstract: Intersex, or the presence of oocytes in the testes, has been documented in fish following exposure to wastewater effluent and estrogenic compounds. However, the molecular networks underlying the intersex condition are not completely known. To address this, we exposed male fathead minnows to a low, environmentally-relevant concentration of 17alpha-ethinylestradiol (EE2) (15 ng/L) and measured the transcriptome response in the testis after 96 h to identify early molecular initiating events that may proceed the intersex condition. The short-term exposure to EE2 did not affect gonadosomatic index and proportion of gametes within the testes. However, the production of 11-ketotestosterone and testosterone from the testis in vitro was decreased relative to controls. Expression profiling using a 8 × 60 K fathead minnow microarray identified 10 transcripts that were differentially expressed in the testes, the most dramatic change being that of coagulation factor XIII A chain (20-fold increase). Transcripts that included guanine nucleotide binding protein (Beta Polypeptide 2), peroxisome proliferator-activated receptor delta, and WNK lysine deficient protein kinase 1a, were down-regulated by EE2. Subnetwork enrichment analysis revealed that EE2 suppressed transcriptional networks associated with steroid metabolism, hormone biosynthesis, and sperm mobility. Most interesting was that gene networks associated with doublesex and mab-3 related transcription factor 1 (dmrt1) were suppressed in the adult

  4. Low dose diagnostic radiation does not increase cancer risk in cancer prone mice

    Energy Technology Data Exchange (ETDEWEB)

    Boreham, D., E-mail: dboreham@nosm.ca [Northern Ontario School of Medicine, ON (Canada); Phan, N., E-mail: nghiphan13@yahoo.com [Univ. of Ottawa, Ottawa, ON (Canada); Lemon, J., E-mail: lemonja@mcmaster.ca [McMaster Univ., Hamilton, ON (Canada)

    2014-07-01

    The increased exposure of patients to low dose diagnostic ionizing radiation has created concern that these procedures will result in greater risk of carcinogenesis. However, there is substantial evidence that shows in many cases that low dose exposure has the opposite effect. We have investigated whether CT scans can modify mechanisms associated with carcinogenesis in cancer-prone mice. Cancer was induced in Trp53+/- mice with an acute high dose whole-body 4 Gy γ-radiation exposure. Four weeks following the cancer-inducing dose, weekly whole-body CT scans (10 mGy/scan, 75 kVp X-rays) were given for ten consecutive weeks adding an additional radiation burden of 0.1 Gy. Short-term biological responses and subsequent lifetime cancer risk were investigated. Five days following the last CT scan, there were no detectable differences in the spontaneous levels of DNA damage in blood cells (reticulocytes). In fact, CT scanned mice had significantly lower constitutive levels of oxidative DNA damage and cell death (apoptosis), compared to non-CT scanned mice. This shows that multiple low dose radiation exposures modified the radio response and indicates protective processes were induced in mice. In mice treated with the multiple CT scans following the high cancer-inducing 4 Gy dose, tumour latency was increased, significantly prolonging lifespan. We conclude that repeated CT scans can reduce the cancer risk of a prior high-dose radiation exposure, and delay the progression of specific types of radiation-induced cancers in Trp53+/-mice. This research shows for the first time that low dose exposure long after cancer initiation events alter risk and reduce cancer morbidity. Cancer induction following low doses does not follow a linear non-threshold model of risk and this model should not be used to extrapolate risk to humans following low dose exposure to ionizing radiation. (author)

  5. The health effects of low-dose ionizing radiation

    International Nuclear Information System (INIS)

    Dixit, A.N.; Dixit, Nishant

    2012-01-01

    It has been established by various researches, that high doses of ionizing radiation are harmful to health. There is substantial controversy regarding the effects of low doses of ionizing radiation despite the large amount of work carried out (both laboratory and epidemiological). Exposure to high levels of radiation can cause radiation injury, and these injuries can be relatively severe with sufficiently high radiation doses. Prolonged exposure to low levels of radiation may lead to cancer, although the nature of our response to very low radiation levels is not well known at this time. Many of our radiation safety regulations and procedures are designed to protect the health of those exposed to radiation occupationally or as members of the public. According to the linear no-threshold (LNT) hypothesis, any amount, however small, of radiation is potentially harmful, even down to zero levels. The threshold hypothesis, on the other hand, emphasizes that below a certain threshold level of radiation exposure, any deleterious effects are absent. At the same time, there are strong arguments, both experimental and epidemiological, which support the radiation hormesis (beneficial effects of low-level ionizing radiation). These effects cannot be anticipated by extrapolating from harmful effects noted at high doses. Evidence indicates an inverse relationship between chronic low-dose radiation levels and cancer incidence and/or mortality rates. Examples are drawn from: 1) state surveys for more than 200 million people in the United States; 2) state cancer hospitals for 200 million people in India; 3) 10,000 residents of Taipei who lived in cobalt-60 contaminated homes; 4) high-radiation areas of Ramsar, Iran; 5) 12 million person-years of exposed and carefully selected control nuclear workers; 6) almost 300,000 radon measurements of homes in the United States; and 7) non-smokers in high-radon areas of early Saxony, Germany. This evidence conforms to the hypothesis that

  6. Risk of radiation-induced cancer at low doses and low dose rates for radiation protection purposes

    International Nuclear Information System (INIS)

    1995-01-01

    The aim of this report is to provide an updated, comprehensive review of the data available for assessing the risk of radiation-induced cancer for radiation protection purposes. Particular emphasis is placed on assessing risks at low doses and low dose rates. The review brings together the results of epidemiological investigations and fundamental studies on the molecular and cellular mechanisms involved in radiation damage. Additionally, this information is supplemented by studies with experimental animals which provide further guidance on the form of the dose-response relationship for cancer induction, as well as on the effect of dose rate on the tumour yield. The emphasis of the report is on cancer induction resulting from exposure to radiations with a low linear energy transfer (LET). The work was performed under contract for the Institut de Protection et de Surete Nucleaire, Fontenay-aux-Roses, Paris, France, whose agreement to publish is gratefully ackowledged. It extends the advice on radiation risks given in Documents of the NRPB, 4 No. 4 (1993). (Author)

  7. 'Reasonable' regulation of low doses in the Netherlands?

    International Nuclear Information System (INIS)

    Zuur, Ciska

    2002-01-01

    As long as it is not clear exactly what the risks of low doses are, exposures should be regulated to be 'as low as reasonably achievable' (ALARA). In radiation protection, for normal situations, this means that a projected dose reduction can only be obligatory when the efforts needed to achieve the reduction are 'reasonable' in comparison with it, economical and social aspects being taken into account. In the recent Dutch regulations, 'reasonable' values have been established for the relevant parameters used in the ALARA concept and the paper discusses the values required to calculate the doses for the critical group due to a source. In some cases, the effort expended in making the ALARA dose assessments might not be reasonable in comparison with the dose reduction to be expected. The system which has been developed in the Netherlands to avoid these 'unreasonable' dose calculations, measurements and assessments is explained. (author)

  8. low dose irradiation growth in zirconium

    International Nuclear Information System (INIS)

    Fortis, A.M.

    1987-01-01

    Low dose neutron irradiation growth in textured and recrystallized zirconium, is studied, at the Candu Reactors Calandria temperature (340 K) and at 77 K. It was necessary to design and build 1: A facility to irradiate at high temperatures, which was installed in the Argentine Atomic Energy Commission's RA1 Reactor; 2: Devices to carry out thermal recoveries, and 3: Devices for 'in situ' measurements of dimensional changes. The first growth kinetics curves were obtained at 365 K and at 77 K in a cryostat under neutron fluxes of similar spectra. Irradiation growth experiments were made in zirconium doped with fissionable material (0,1 at % 235 U). In this way an equivalent dose two orders of magnitude greater than the reactor's fast neutrons dose was obtained, significantly reducing the irradiation time. The specimens used were bimetallic couples, thus obtaining a great accuracy in the measurements. The results allow to determine that the dislocation loops are the main cause of irradiation growth in recrystallized zirconium. Furthermore, it is shown the importance of 'in situ' measurements as a way to avoid the effect that temperature changes have in the final growth measurement; since they can modify the residual stresses and the overconcentrations of defects. (M.E.L.) [es

  9. Cardiovascular risks associated with low dose ionizing particle radiation.

    Directory of Open Access Journals (Sweden)

    Xinhua Yan

    Full Text Available Previous epidemiologic data demonstrate that cardiovascular (CV morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ((1H; 0.5 Gy, 1 GeV and iron ion ((56Fe; 0.15 Gy, 1GeV/nucleon irradiation with and without an acute myocardial ischemia (AMI event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in (56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  10. Cytogenetic Low-Dose Hyperradiosensitivity Is Observed in Human Peripheral Blood Lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Seth, Isheeta [Department of Biological Sciences, Wayne State University, Detroit, Michigan (United States); Joiner, Michael C. [Department of Radiation Oncology, Wayne State University, Detroit, Michigan (United States); Tucker, James D., E-mail: jtucker@biology.biosci.wayne.edu [Department of Biological Sciences, Wayne State University, Detroit, Michigan (United States)

    2015-01-01

    Purpose: The shape of the ionizing radiation response curve at very low doses has been the subject of considerable debate. Linear-no-threshold (LNT) models are widely used to estimate risks associated with low-dose exposures. However, the low-dose hyperradiosensitivity (HRS) phenomenon, in which cells are especially sensitive at low doses but then show increased radioresistance at higher doses, provides evidence of nonlinearity in the low-dose region. HRS is more prominent in the G2 phase of the cell cycle than in the G0/G1 or S phases. Here we provide the first cytogenetic mechanistic evidence of low-dose HRS in human peripheral blood lymphocytes using structural chromosomal aberrations. Methods and Materials: Human peripheral blood lymphocytes from 2 normal healthy female donors were acutely exposed to cobalt 60 γ rays in either G0 or G2 using closely spaced doses ranging from 0 to 1.5 Gy. Structural chromosomal aberrations were enumerated, and the slopes of the regression lines at low doses (0-0.4 Gy) were compared with doses of 0.5 Gy and above. Results: HRS was clearly evident in both donors for cells irradiated in G2. No HRS was observed in cells irradiated in G0. The radiation effect per unit dose was 2.5- to 3.5-fold higher for doses ≤0.4 Gy than for doses >0.5 Gy. Conclusions: These data provide the first cytogenetic evidence for the existence of HRS in human cells irradiated in G2 and suggest that LNT models may not always be optimal for making radiation risk assessments at low doses.

  11. Radiation protection and environment day the low doses in everyday life

    International Nuclear Information System (INIS)

    2007-01-01

    The consequences of low doses exposures are difficult to explore and the studies give often place to controversies. According to the are, differences exist in the methodological approaches. It results from it a confusion on the acceptable levels of exposure, even on the definition of low dose. This day organised by the sections 'non ionizing and research and health of the French society of radiation protection (S.F.R.P.), will be a meeting between professionals of different disciplines, to compare the approaches used for the ionizing and non ionizing radiations as well as the chemical and microbiological agents. It will allow to share the knowledge and the abilities and to progress on methodologies adapted to the evaluation and the management of risks in relation with low doses. (N.C.)

  12. Mutation induction in cultured human cells after low-dose and low-dose-rate γ-ray irradiation. Detection by LOH analysis

    International Nuclear Information System (INIS)

    Umebayashi, Yukihiro; Iwaki, Masaya; Yatagai, Fumio; Honma, Masamitsu; Suzuki, Masao; Suzuki, Hiromi; Shimazu, Toru; Ishioka, Noriaki

    2007-01-01

    To study the genetic effects of low-doses and low-dose-rate ionizing radiation (IR), human lymphoblastoid TK6 cells were exposed to 30 mGy of γ-rays at a dose-rate of 1.2 mGy/hr. The frequency of early mutations (EMs) in the thymidine kinase (TK) gene locus was determined to be 1.7 x 10 -6 , or 1.9-fold higher than the level seen in unirradiated controls. These mutations were analyzed with a loss of heterozygosity (LOH) detection system, a methodology which has been shown to be sensitive to the effects of radiation. Among the 15 EMs observed after IR exposure, 8 were small interstitial-deletion events restricted to the TK gene locus. However, this specific type of event was not found in unirradiated controls. Although these results were observed under the limited conditions, they strongly suggest that the LOH detection system can be used for estimating the genetic effects of a low-dose IR exposure delivered at a low-dose-rate. (author)

  13. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cheryl G. Burrell, Ph.D.

    2012-05-14

    The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

  14. Efficacy of the Tertiary Oxime Monoisonitrosoacetone (MINA) Against Lethal Sarin Intoxication in the Guinea Pig

    Science.gov (United States)

    2007-10-01

    Sarin 5a. CONTRACT NUMBER Intoxication in the Guinea Pig 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Koplovitz, I and...efficacy of MINA as a treatment for lethal sarin (GB) intoxication in guinea pigs . Male animals were challenged subcutaneously (s.c.) with 2 LD50s...oximes that are readily able to enter the brain. 15. SUBJECT TERMS oximes, brain, sarin, reactivation, nerve agents, guinea pigs 16. SECURITY

  15. Characteristics of repair following very low doses

    International Nuclear Information System (INIS)

    Braby, L.A.; Metting, N.F.; Nelson, J.M.

    1987-01-01

    The effects of ionizing radiation on living systems being with the physical processes of energy deposition and develop through many stages of chemical reaction and biological response. The modeling effort attempts to organize the available data and theories of all of these stages into self-consistent models that can be compared and tested. In some cases, important differences among models result in only small differences in cell survival within the ranges of dose and dose rate that are normally investigated. To overcome this limitation, new ways of irradiating cells at extremes of dose rate, or ways of evaluating the effects of very small doses, are developed. Mathematical modeling and cellular studies complement each other. It has recently been found that some mechanisms are not adequate to account for the interaction of dose and repair time as they affect the reproductive survival of plateau-phase Chinese hamster ovary (CHO) cells. Repair of radiation-induced cellular damage plays a central role in the survival of cells exposed to doses of 1 Gy or more. This repair is responsible for the dose rate, split-dose and delayed plating effect and can be evaluated. Because split-dose and dose-rate experiments involve repair during irradiation and delayed plating experiments involve repair after irradiation is completed, it was originally thought that different repair processes were involved. It is now clear that this is not necessarily the case. Appropriately designed models can account for observed effects at conventional doses (1 Gy or more) whether they assume all damage is lethal unless repaired or some damage is innocuous unless it interacts with additional damage. The fact that the survival following a plating delay is always less than the survival following immediate plating at low doses indicates that the damage produced is probably not potentially lethal

  16. Effects of low dose mitomycin C on experimental tumor radiotherapy

    International Nuclear Information System (INIS)

    Yang Jianzheng; Liang Shuo; Qu Yaqin; Pu Chunji; Zhang Haiying; Wu Zhenfeng; Wang Xianli

    2001-01-01

    Objective: To evaluate the possibility of low dose mitomycin C(MMC) as an adjunct therapy for radiotherapy. Methods: Change in tumor size tumor-bearing mice was measured. Radioimmunoassay was used to determine immune function of mice. Results: Low dose Mac's pretreatment reduced tumor size more markedly than did radiotherapy only. The immune function in mice given with low dose MMC 12h before radiotherapy was obviously higher than that in mice subjected to radiotherapy only (P<0.05), and was close to that in the tumor-bearing mice before radiotherapy. Conclusion: Low dose MMC could improve the radiotherapy effect. Pretreatment with low dose MMC could obviously improve the immune suppression state in mice caused by radiotherapy. The mechanism of its improvement of radiotherapeutic effect by low dose of MMC might be due to its enhancement of immune function and induction of adaptive response in tumor-bearing mice

  17. Low-dose effects of hormones and endocrine disruptors.

    Science.gov (United States)

    Vandenberg, Laura N

    2014-01-01

    Endogenous hormones have effects on tissue morphology, cell physiology, and behaviors at low doses. In fact, hormones are known to circulate in the part-per-trillion and part-per-billion concentrations, making them highly effective and potent signaling molecules. Many endocrine-disrupting chemicals (EDCs) mimic hormones, yet there is strong debate over whether these chemicals can also have effects at low doses. In the 1990s, scientists proposed the "low-dose hypothesis," which postulated that EDCs affect humans and animals at environmentally relevant doses. This chapter focuses on data that support and refute the low-dose hypothesis. A case study examining the highly controversial example of bisphenol A and its low-dose effects on the prostate is examined through the lens of endocrinology. Finally, the chapter concludes with a discussion of factors that can influence the ability of a study to detect and interpret low-dose effects appropriately. © 2014 Elsevier Inc. All rights reserved.

  18. Clinical application of low-dose spiral CT for orthodontics

    International Nuclear Information System (INIS)

    Xie Na; Gan Yungen; Shu Huang; Lin FeiFei; Li Zhiyong; Sun Jie

    2009-01-01

    Objective: To determine the effect of reducing the value of mA or kV on the image quality and the radiation dose of the patients undergoing low-dose spiral CT for orthodontics. Methods: Thirty patients were divided into three groups, each group has 10 patients. They were group 1 (80 kV and 200 mA), group 2 (120 kV and 80 mA), group 3 (120 kV and 200 mA) The volume CT dose index (CTDI) was recorded and the average dose-length produce (DLP) was calculated in three groups,respectively. Image quality of three groups were compared and scored by two radiologists, and the results were statistically analysed. Results: The CTDI and DLP of 80 kV group (group 2) were 8.7 mGy and (36.80 ± 3.60) mGy · cm, respectively, those of 80 mA group (group 3) were 19.6 mGy and (82.14 ± 7.18) mGy · cm, respectively, and those of conventional-dose group (group 1) were 19.6 mGy and (82.14 ± 7.18) mGy · cm, respectively. There was no significant difference among three groups in diagnostic image quality. Conclusions: Low-dose spiral CT for orthodontics, especially the low-kV scan, may decrease the radiation exposure and guarantee the image quality. (authors)

  19. Implications of effects ''adaptive response'', ''low-dose hypersensitivity'' und ''bystander effect'' for cancer risk at low doses and low dose rates

    International Nuclear Information System (INIS)

    Jacob, P

    2006-01-01

    A model for carcinogenesis (the TSCE model) was applied in order to examine the effects of ''Low-dose hypersensitivity (LDH)'' and the ''Bystander effect (BE)'' on the derivation of radiation related cancer mortality risks. LDH has been discovered to occur in the inactivation of cells after acute exposure to low LET radiation. A corresponding version of the TSCE model was applied to the mortality data on the Abomb survivors from Hiroshima and Nagasaki. The BE has been mainly observed in cells after exposure to high LET radiation. A Version of the TSCE model which included the BE was applied to the data on lung cancer mortality from the workers at the Mayak nuclear facilities who were exposed to Plutonium. In general an equally good description of the A-bomb survivor mortality data (for all solid, stomach and lung tumours) was found for the TSCE model and the (conventional) empirical models but fewer parameters were necessary for the TSCE model. The TSCE model which included the effects of radiation induced cell killing resulted in non-linear dose response curves with excess relative risks after exposure at young ages that were generally lower than in the models without cell killing. The main results from TSCE models which included cell killing described by either conventional survival curves or LDH were very similar. A sub multiplicative effect from the interaction of smoking and exposure to plutonium was found to result from the analysis of the Mayak lung cancer mortality data. All models examined resulted in the predominant number of Mayak lung cancer deaths being ascribed to smoking. The interaction between smoking and plutonium exposures was found to be the second largest effect. The TSCE model resulted in lower estimates for the lung cancer excess relative risk per unit plutonium dose than the empirical risk model, but this difference was not found to be statistically significant. The excess relative risk dose responses were linear in the empirical model and

  20. Pathways for the Oxidation of Sarin in Urban Atmospheres

    Energy Technology Data Exchange (ETDEWEB)

    Gerald E. Streit; James E. Bossert; Jeffrey S. Gaffney; Jon Reisner; Laurie A. McNair; Michael Brown; Scott Elliott

    1998-11-01

    Terrorists have threatened and carried out chemicalhiological agent attacks on targets in major cities. The nerve agent sarin figured prominently in one well-publicized incident. Vapors disseminating from open containers in a Tokyo subway caused thousands of casualties. High-resolution tracer transport modeling of agent dispersion is at hand and will be enhanced by data on reactions with components of the urban atmosphere. As a sample of the level of complexity currently attainable, we elaborate the mechanisms by which sarin can decompose in polluted air. A release scenario is outlined involving the passage of a gas-phase agent through a city locale in the daytime. The atmospheric chemistry database on related organophosphorus pesticides is mined for rate and product information. The hydroxyl,radical and fine-mode particles are identified as major reactants. A review of urban air chernistry/rnicrophysics generates concentration tables for major oxidant and aerosol types in both clean and dirty environments. Organic structure-reactivity relationships yield an upper limit of 10-1' cm3 molecule-' S-* for hydrogen abstraction by hydroxyl. The associated midday loss time scale could be as little as one hour. Product distributions are difficult to define but may include nontoxic organic oxygenates, inorganic phosphorus acids, sarin-like aldehydes, and nitrates preserving cholinergic capabilities. Agent molecules will contact aerosol surfaces in on the order of minutes, with hydrolysis and side-chain oxidation as likely reaction channels.

  1. Nanocrystalline zinc oxide for the decontamination of sarin

    Energy Technology Data Exchange (ETDEWEB)

    Mahato, T.H. [Defense R and D Establishment, Jhansi Road, 474002, Gwalior, MP (India); Prasad, G.K., E-mail: gkprasad@lycos.com [Defense R and D Establishment, Jhansi Road, 474002, Gwalior, MP (India); Singh, Beer; Acharya, J.; Srivastava, A.R.; Vijayaraghavan, R. [Defense R and D Establishment, Jhansi Road, 474002, Gwalior, MP (India)

    2009-06-15

    Nanocrystalline zinc oxide materials were prepared by sol-gel method and were characterized by X-ray diffraction, scanning electron microscopy, thermogravimetry, nitrogen adsorption and infrared spectroscopy techniques. The data confirmed the formation of zinc oxide materials of zincite phase with an average crystallite size of {approx}55 nm. Obtained material was tested as destructive adsorbent for the decontamination of sarin and the reaction was followed by GC-NPD and GC-MS techniques. The reaction products were characterized by GC-MS and the data explored the role of hydrolysis reaction in the detoxification of sarin. Sarin was hydrolyzed to form surface bound non-toxic phosphonate on the surface of nano-zinc oxide. The data also revealed the values of rate constant and half-life to be 4.12 h{sup -1} and 0.16 h in the initial stages of the reaction and 0.361 h{sup -1} and 1.9 h at the final stages of the reaction for the decontamination reaction on nanocrystalline ZnO.

  2. Nanocrystalline zinc oxide for the decontamination of sarin

    International Nuclear Information System (INIS)

    Mahato, T.H.; Prasad, G.K.; Singh, Beer; Acharya, J.; Srivastava, A.R.; Vijayaraghavan, R.

    2009-01-01

    Nanocrystalline zinc oxide materials were prepared by sol-gel method and were characterized by X-ray diffraction, scanning electron microscopy, thermogravimetry, nitrogen adsorption and infrared spectroscopy techniques. The data confirmed the formation of zinc oxide materials of zincite phase with an average crystallite size of ∼55 nm. Obtained material was tested as destructive adsorbent for the decontamination of sarin and the reaction was followed by GC-NPD and GC-MS techniques. The reaction products were characterized by GC-MS and the data explored the role of hydrolysis reaction in the detoxification of sarin. Sarin was hydrolyzed to form surface bound non-toxic phosphonate on the surface of nano-zinc oxide. The data also revealed the values of rate constant and half-life to be 4.12 h -1 and 0.16 h in the initial stages of the reaction and 0.361 h -1 and 1.9 h at the final stages of the reaction for the decontamination reaction on nanocrystalline ZnO.

  3. Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides

    National Research Council Canada - National Science Library

    Lockridge, Oksana

    2003-01-01

    Though acetylcholinesterase is the primary target of organophosphorus toxicants, our finding that acetylcholinesterase knockout mice are supersensitive to the lethal effects of VX, DFP, chlorpyrifos...

  4. Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides

    National Research Council Canada - National Science Library

    Lockridge, Oksana

    2004-01-01

    Though acetylcholinesterase is the primary target of organophosphorus toxicants, our finding that acetylcholinesterase knockout mice are supersensitive to the lethal effects of VX, DFP, chlorpyrifos...

  5. Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides

    National Research Council Canada - National Science Library

    Lockridge, Oksana

    2002-01-01

    Though acetyicholinesterase is the primary target of organophosphorus toxicants, our finding that acetyicholinesterase knockout mice are supersensitive to the lethal effects of VX, DFP, chlorpyrifos...

  6. Cancer risk at low doses of ionizing radiation. Artificial neural networks inference from atomic bomb survivors

    International Nuclear Information System (INIS)

    Sasaki, Masao S.; Tachibana, Akira; Takeda, Shunichi

    2014-01-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (1) the presence of a threshold that varied with organ, gender and age at exposure, and (2) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to 239 Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation–environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking. (author)

  7. Low doses effects of ionizing radiation on Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Durand, J.; Broock, M. van; Gillette, V.H.

    2000-01-01

    The exposure of living cells to low doses of ionizing radiation induce in response the activation of cellular protection mechanisms against subsequent larger doses of radiation. This cellular adaptive response may vary depending on radiation intensity and time of exposure, and also on the testing probes used whether they were mammalian cells, yeast, bacteria and other organisms or cell types. The mechanisms involved are the genome activation, followed by DNA repair enzymes synthesis. Due to the prompt cell response, the cell cycle can be delayed, and the secondary detoxification of free radicals and/or activation of membrane bound receptors may proceed. All these phenomena are submitted to intense scientific research nowadays, and their elucidation will depend on the complexity of the organism under study. In the present work, the effects of low doses of ionizing radiation (gamma rays) over a suspension of the yeast Saccharomyces cerevisiae (Baker's yeast) was studied, mainly in respect to survival rate and radio-adaptive response. At first, the yeast surviving curve was assessed towards increasing doses, and an estimation of Lethal Dose 50 (LD50) was made. The irradiation tests were performed at LINAC (electrons Linear Accelerator) where electron energy reached approximately 2.65 MeV, and gamma-radiation was produced for bremsstrahlung process over an aluminium screen target. A series of experiments of conditioning doses was performed and an increment surviving fraction was observed when the dose was 2.3 Gy and a interval time between this and a higher dose (challenging dose) of 27 Gy was 90 minutes. A value of 58 ± 4 Gy was estimated for LD50, at a dose rate of 0.44 ± 0.03 Gy/min These quantities must be optimized. Besides data obtained over yeast survival, an unusual increasing amount of tiny yeast colonies appeared on the agar plates after incubation, and this number increased as increasing the time exposure. Preliminary results indicate these colonies as

  8. Cancer and low dose responses in vivo: implications for radiation protection

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.

    2006-01-01

    Full text: Radiation protection practices assume that cancer risk is linearly proportional to total dose, without a threshold, both for people with normal cancer risk and for people who may be genetically cancer prone. Mice heterozygous for the Tp 53 gene are cancer prone, and their increased risk from high doses was not different from Tp 53 normal mice. However, in either Tp 53 normal or heterozygous mice, a single low dose of low LET radiation given at low dose rate protected against both spontaneous and radiation-induced cancer by increasing tumor latency. Increased tumor latency without a cancer frequency change implies that low doses in vivo primarily slow the process of genomic instability, consistent with the elevated capacity for correct DSB rejoining seen in low dose exposed cells. The in vivo animal data indicates that, for low doses and low dose rates in both normal and cancer prone adult mice, risk does not increase linearly with dose, and dose thresholds for increased risk exist. Below those dose thresholds (which are influenced by Tp 53 function) overall risk is reduced below that of unexposed control mice, indicating that Dose Rate Effectiveness Factors (DREF) may approach infinity, rather than the current assumption of 2. However, as dose decreases, different tissues appear to have different thresholds at which detriment turns to protection, indicating that individual tissue weighting factors (Wt) are also not constant, but vary from positive values to zero with decreasing dose. Measurements of Relative Biological Effect between high and low LET radiations are used to establish radiation weighting factors (Wr) used in radiation protection, and these are also assumed to be constant with dose. However, since the risk from an exposure to low LET radiation is not constant with dose, it would seem unlikely that radiation-weighting factors for high LET radiation are actually constant at low dose and dose rate

  9. A new study on the effects of low doses

    International Nuclear Information System (INIS)

    Dousset, M.; Jammet, H.

    1986-01-01

    A study conducted by prof. Rose has investigated mortality among 39540 employees of the UKAEA, from 1946 to 1978. The three main points are: 1. General mortality and mortality from malignant diseases are lower than in the population of England and Wales (74 and 79 per cent respectively), thus showing no major difference between workers monitored for exposure to radiation and other workers. 2. For monitored workers, the only death cause for which there is a statistically significant correlation with radiation exposure is prostate cancer; there are many cases especially in workers with doses exceeding 0.05 Sv (5 rem) and monitored for tritium. Such a correlation has never been found in any other epidemiologic survey of workers exposed to low-level doses, Hanford (USA) workers especially; conversely, mortality from either multiple myeloma or pancreas cancer is not found here. These facts plead for a cautious interpretation of the results as a whole. 3. A linear representation of the variations of leukemia and cancer mortality vs exposure results in lines, the slopes of which are 3 times higher than those of the lines adopted by ICRP; however, the 95% confidence intervals (-2.7 + 12.4 and -22 + 52.5) are such that the results are compatible with a null effect (slope 0) and even with a benefic effect (negative slope). They are therefore compatible with ICRP estimations. A recent attempt to evaluate the two main investigations on low-dose occupational exposures (UKAEA and Hanford) suggests a dose-response relationship very near that of ICRP [fr

  10. Low-dose aspirin or other nonsteroidal anti-inflammatory drug use and prostate cancer risk

    DEFF Research Database (Denmark)

    Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael

    2016-01-01

    PURPOSE: Increasing evidence suggests that aspirin use may protect against prostate cancer. In a nationwide case-control study, using Danish high-quality registry data, we evaluated the association between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs......) and the risk of prostate cancer. METHODS: We identified 35,600 patients (cases) with histologically verified prostate cancer during 2000-2012. Cases were matched to 177,992 population controls on age and residence by risk-set sampling. Aspirin and nonaspirin NSAID exposure was defined by type, estimated dose......, duration, and consistency of use. We used conditional logistic regression to estimate odds ratios (ORs), with 95 % confidence intervals (CIs), for prostate cancer associated with low-dose aspirin (75-150 mg) or nonaspirin NSAID use, adjusted for potential confounders. RESULTS: Use of low-dose aspirin...

  11. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    International Nuclear Information System (INIS)

    Feinendegen, L.E.; Sondhaus, C.A.; Altman, K.I.

    1998-01-01

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts

  12. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    International Nuclear Information System (INIS)

    Chen Yang; Shi Luyao; Shu Huazhong; Luo Limin; Coatrieux, Jean-Louis; Yin Xindao; Toumoulin, Christine

    2013-01-01

    In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors. (paper)

  13. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.; Bond, V.P. [Washington State Univ., Richland, WA (United States); Sondhaus, C.A. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Radiology and Radiation Control Office; Altman, K.I. [Univ. of Rochester Medical Center, NY (United States). Dept. of Biochemistry and Biophysics

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

  14. Low-dose CT image reconstruction using gain intervention-based dictionary learning

    Science.gov (United States)

    Pathak, Yadunath; Arya, K. V.; Tiwari, Shailendra

    2018-05-01

    Computed tomography (CT) approach is extensively utilized in clinical diagnoses. However, X-ray residue in human body may introduce somatic damage such as cancer. Owing to radiation risk, research has focused on the radiation exposure distributed to patients through CT investigations. Therefore, low-dose CT has become a significant research area. Many researchers have proposed different low-dose CT reconstruction techniques. But, these techniques suffer from various issues such as over smoothing, artifacts, noise, etc. Therefore, in this paper, we have proposed a novel integrated low-dose CT reconstruction technique. The proposed technique utilizes global dictionary-based statistical iterative reconstruction (GDSIR) and adaptive dictionary-based statistical iterative reconstruction (ADSIR)-based reconstruction techniques. In case the dictionary (D) is predetermined, then GDSIR can be used and if D is adaptively defined then ADSIR is appropriate choice. The gain intervention-based filter is also used as a post-processing technique for removing the artifacts from low-dose CT reconstructed images. Experiments have been done by considering the proposed and other low-dose CT reconstruction techniques on well-known benchmark CT images. Extensive experiments have shown that the proposed technique outperforms the available approaches.

  15. What can be learned from epidemiologic studies of persons exposed to low doses of radiation?

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1993-04-01

    The main objective of radiation risk assessment is to determine the risk of various adverse health effects associated with exposure to low doses and low dose rates. Extrapolation of risks from studies of persons exposed at high doses (generally exceeding 1 Sv) and dose rates has been the primary approach used to achieve this objective. The study of Japanese atomic bomb survivors in Hiroshima and Nagasaki has played an especially important role in risk assessment efforts. A direct assessment of the dose-response function based on studies of persons exposed at low doses and dose rates is obviously desirable. This paper focuses on the potential of both current and future nuclear workers studies for investigating the dose-response functions at low doses, and also discusses analyses making use of the low dose portion of the atomic bomb survivor data. Difficulties in using these data are the statistical imprecision of estimated dose-response parameters, and potential bias resulting from confounding factors and from uncertainties in dose estimates

  16. Dose rate effect on low-dose hyper-radiosensitivity with cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Geon-Min; Kim, Eun-Hee [Seoul National University, Seoul (Korea, Republic of)

    2016-10-15

    Low-dose hyper-radiosensitivity (HRS) is the phenomenon that mammalian cells exhibit higher sensitivity to radiation at low doses (< 0.5 Gy) than expected by the linear-quadratic model. At doses above 0.5Gy, the cellular response is recovered to the level expected by the linear-quadratic model. This transition is called the increased radio-resistance (IRR). HRS was first verified using Chinese hamster V79 cells in vitro by Marples and has been confirmed in studies with other cell lines including human normal and tumor cells. HRS is known to be induced by inactivation of ataxia telangiectasia-mutated (ATM), which plays a key role in repairing DNA damages. Considering the connection between ATM and HRS, one can infer that dose rate may affect cellular response regarding HRS at low doses. In this study, we quantitated the effect of dose rate on HRS by clonogenic assay with normal and tumor cells. The HRS of cells at low dose exposures is a phenomenon already known. In this study, we observed HRS of rat normal diencephalon cells and rat gliosarcoma cells at doses below 1 Gy. In addition, we found that dose rate mattered. HRS occurred at low doses, but only when total dose was delivered at a rate below certain level.

  17. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  18. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  19. Lab-on-a-chip for rapid electrochemical detection of nerve agent Sarin

    DEFF Research Database (Denmark)

    Tan, Hsih-Yin; Loke, Weng Keong; Nguyen, Nam-Trung

    2014-01-01

    This paper reports a lab-on-a-chip for the detection of Sarin nerve agent based on rapid electrochemical detection. The chemical warfare agent Sarin (C4H10FO2P, O-isopropyl methylphosphonofluoridate) is a highly toxic organophosphate that induces rapid respiratory depression, seizures and death...

  20. Lung cancer risk at low doses of alpha particles

    International Nuclear Information System (INIS)

    Hofmann, W.; Katz, R.; Zhang, C.X.

    1986-01-01

    A survey of inhabitant exposures arising from the inhalation of 222 Rn and 220 Rn progeny, and lung cancer mortality has been carried out in two adjacent areas in Guangdong Province, People's Republic of China, designated as the high background and the control area. Annual exposure rates are 0.38 working level months (WLM) per year in the high background, and 0.16 WLM/yr in the control area. In 14 yr of continuous study, from 1970 to 1983, age-adjusted mortality rates were found to be 2.7 per 10(5) living persons of all ages in the high background area, and 2.9 per 10(5) living persons in the control area. From this data, we conclude that we are unable to determine excess lung cancers over the normal fluctuations below a cumulative exposure of 15 WLM. This conclusion is supported by lung cancer mortality data from Austrian and Finnish high-background areas. A theoretical analysis of epidemiological data on human lung cancer incidence from inhaled 2 ]2'' 2 Rn and 220 Rn progeny, which takes into account cell killing as competitive with malignant transformation, leads to the evaluation of a risk factor which is either a linear-exponential or a quadratic-exponential function of the alpha-particle dose. Animal lung cancer data and theoretical considerations can be supplied to support either hypothesis. Thus we conclude that at our current stage of knowledge both the linear-exponential and the quadratic-exponential extrapolation to low doses seem to be equally acceptable for Rn-induced lung cancer risk, possibly suggesting a linear-quadratic transformation function with an exponential cell-killing term, or the influence of risk-modifying factors such as repair or proliferation stimuli

  1. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    Science.gov (United States)

    2011-01-01

    Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p.) 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.). IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v.) prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical) given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA. PMID:22114930

  2. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    Directory of Open Access Journals (Sweden)

    Mayado Andrea

    2011-11-01

    Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

  3. Low dose radiation prevents doxorubicin-induced cardiotoxicity.

    Science.gov (United States)

    Jiang, Xin; Hong, Yaqiong; Zhao, Di; Meng, Xinxin; Zhao, Lijing; Du, Yanwei; Wang, Zan; Zheng, Yan; Cai, Lu; Jiang, Hongyu

    2018-01-02

    This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling.

  4. Biological effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Gonzalez, A.J.

    1994-01-01

    Few weeks ago, when the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) submitted to the U.N. General Assembly the UNSCEAR 1994 report, the international community had at its disposal a broad view of the biological effects of low doses of ionizing radiation. The 1994 report (272 pages) specifically addressed the epidemiological studies of radiation carcinogenesis and the adaptive responses to radiation in cells and organisms. The report was aimed to supplement the UNSCEAR 1993 report to the U.N. General Assembly- an extensive document of 928 pages-which addressed the global levels of radiation exposing the world population, as well as some issues on the effects of ionizing radiation, including: mechanisms of radiation oncogenesis due to radiation exposure, influence of the level of dose and dose rate on stochastic effects of radiation, hereditary effects of radiation effects on the developing human brain, and the late deterministic effects in children. Those two UNSCEAR reports taken together provide an impressive overview of current knowledge on the biological effects of ionizing radiation. This article summarizes the essential issues of both reports, although it cannot cover all available information. (Author)

  5. Mammalian Tissue Response to Low Dose Ionizing Radiation: The Role of Oxidative Metabolism and Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Azzam, Edouard I

    2013-01-16

    The objective of the project was to elucidate the mechanisms underlying the biological effects of low dose/low dose rate ionizing radiation in organs/tissues of irradiated mice that differ in their susceptibility to ionizing radiation, and in human cells grown under conditions that mimic the natural in vivo environment. The focus was on the effects of sparsely ionizing cesium-137 gamma rays and the role of oxidative metabolism and intercellular communication in these effects. Four Specific Aims were proposed. The integrated outcome of the experiments performed to investigate these aims has been significant towards developing a scientific basis to more accurately estimate human health risks from exposures to low doses ionizing radiation. By understanding the biochemical and molecular changes induced by low dose radiation, several novel markers associated with mitochondrial functions were identified, which has opened new avenues to investigate metabolic processes that may be affected by such exposure. In particular, a sensitive biomarker that is differentially modulated by low and high dose gamma rays was discovered.

  6. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium Annual Meeting of the Environmental Mutagen Society: Agenda and Abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Veigl, Martina L. [Environmental Mutagen Society (EMS), Reston, VA (United States); Case Western Reserve Univ., Cleveland, OH (United States). Case Comprehensive Cancer Center; Morgan, William F. [Univ. of Maryland, College Park, MD (United States); Schwartz, Jeffrey L. [Univ. of Washington, Seattle, WA (United States)

    2009-11-11

    The low dose symposium thoughtfully addressed controversy of risk from low dose radiation exposure, hormesis and radon therapy. The stem cell symposium cogently considered the role of DNA damage and repair in hematopoietic stem cells underlying aging and malignancy and provocatively presented evidence that stem cells may have distinct morphologies and replicative properties, as well as special roles in cancer initiation. In the epigenetics symposium, studies illustrated the long range interaction of epigenetic mechanisms, the roles of CTCF and BORIS in region/specific regulation of epigenetic processes, the impact of DNA damage on epigenetic processes as well as links between epigenetic mechanisms and early nutrition and bystander effects. This report shows the agenda and abstracts for this symposium.

  7. Low-dose radiation employed in diagnostic imaging causes genetic effects in cultured cells

    International Nuclear Information System (INIS)

    Ponzinibbio, Maria V.; Peral-Garcia, Pilar; Seoane, Analia; Crudeli, Cintia

    2010-01-01

    Background: Exposure to environmental, diagnostic, and occupational sources of radiation frequently involves low doses. Although these doses have no immediately noticeable impact on human health there is great interest in their long-term biological effects. Purpose: To assess immediate and time-delayed DNA damage in two cell lines exposed to low doses of ionizing radiation by using the comet assay and micronucleus test, and to compare these two techniques in the analysis of low-dose induced genotoxicity. Material and Methods: CHO and MRC-5 cells were exposed to 50 milliSievert (mSv) of ionizing radiation and assayed immediately after irradiation and at 16 or 12 passages post-irradiation, respectively. Comet assay and micronucleus test were employed. Results: The comet assay values observed in 50 mSv-treated cells were significantly higher than in the control group for both sample times and cell lines (P < 0.001). Micronuclei frequencies were higher in treated cells than in the control group (P < 0.01, CHO cells passage 16; P < 0.05, MRC-5 cells immediately after exposure; P < 0.01 MRC-5 cells passage 12). Correlation analysis between the two techniques was statistically significant (correlation coefficient 0.82, P < 0.05 and correlation coefficient 0.86, P < 0.05 for CHO and MRC-5 cells, respectively). Cells scored at passages 12 or 16 showed more damage than those scored immediately after exposure in both cell lines (no statistically significant differences). Conclusion: Cytomolecular and cytogenetic damage was observed in cells exposed to very low doses of X-rays and their progeny. A single low dose of ionizing radiation was sufficient to induce such response, indicating that mammalian cells are exquisitely sensitive to it. Comet and micronucleus assays are sensitive enough to assess this damage, although the former seems to be more efficient

  8. Low-dose radiation employed in diagnostic imaging causes genetic effects in cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Ponzinibbio, Maria V.; Peral-Garcia, Pilar; Seoane, Analia (Inst. de Genetica Veterinaria, Univ. Nacional de La Plata CONICET, La Plata (Argentina)), e-mail: aseoane@fcv.unlp.edu.ar; Crudeli, Cintia (Agencia Nacional de Promocion Cientifica y Tecnologica, La Plata (Argentina))

    2010-11-15

    Background: Exposure to environmental, diagnostic, and occupational sources of radiation frequently involves low doses. Although these doses have no immediately noticeable impact on human health there is great interest in their long-term biological effects. Purpose: To assess immediate and time-delayed DNA damage in two cell lines exposed to low doses of ionizing radiation by using the comet assay and micronucleus test, and to compare these two techniques in the analysis of low-dose induced genotoxicity. Material and Methods: CHO and MRC-5 cells were exposed to 50 milliSievert (mSv) of ionizing radiation and assayed immediately after irradiation and at 16 or 12 passages post-irradiation, respectively. Comet assay and micronucleus test were employed. Results: The comet assay values observed in 50 mSv-treated cells were significantly higher than in the control group for both sample times and cell lines (P < 0.001). Micronuclei frequencies were higher in treated cells than in the control group (P < 0.01, CHO cells passage 16; P < 0.05, MRC-5 cells immediately after exposure; P < 0.01 MRC-5 cells passage 12). Correlation analysis between the two techniques was statistically significant (correlation coefficient 0.82, P < 0.05 and correlation coefficient 0.86, P < 0.05 for CHO and MRC-5 cells, respectively). Cells scored at passages 12 or 16 showed more damage than those scored immediately after exposure in both cell lines (no statistically significant differences). Conclusion: Cytomolecular and cytogenetic damage was observed in cells exposed to very low doses of X-rays and their progeny. A single low dose of ionizing radiation was sufficient to induce such response, indicating that mammalian cells are exquisitely sensitive to it. Comet and micronucleus assays are sensitive enough to assess this damage, although the former seems to be more efficient

  9. Final Report - Epigenetics of low dose radiation effects in an animal model

    Energy Technology Data Exchange (ETDEWEB)

    Kovalchuk, Olga

    2014-10-22

    This project sought mechanistic understanding of the epigenetic response of tissues as well as the consequences of those responses, when induced by low dose irradiation in a well-established model system (mouse). Based on solid and extensive preliminary data we investigated the molecular epigenetic mechanisms of in vivo radiation responses, particularly – effects of low, occupationally relevant radiation exposures on the genome stability and adaptive response in mammalian tissues and organisms. We accumulated evidence that low dose irradiation altered epigenetic profiles and impacted radiation target organs of the exposed animals. The main long-term goal was to dissect the epigenetic basis of induction of the low dose radiation-induced genome instability and adaptive response and the specific fundamental roles of epigenetic changes (i.e. DNA methylation, histone modifications and miRNAs) in their generation. We hypothesized that changes in global and regional DNA methylation, global histone modifications and regulatory microRNAs played pivotal roles in the generation and maintenance low-dose radiation-induced genome instability and adaptive response. We predicted that epigenetic changes influenced the levels of genetic rearrangements (transposone reactivation). We hypothesized that epigenetic responses from low dose irradiation were dependent on exposure regimes, and would be greatest when organisms are exposed in a protracted/fractionated manner: fractionated exposures > acute exposures. We anticipated that the epigenetic responses were correlated with the gene expression levels. Our immediate objectives were: • To investigate the exact nature of the global and locus-specific DNA methylation changes in the LDR exposed cells and tissues and dissect their roles in adaptive response • To investigate the roles of histone modifications in the low dose radiation effects and adaptive response • To dissect the roles of regulatory microRNAs and their targets in low

  10. Risk of cancer subsequent to low-dose radiation

    International Nuclear Information System (INIS)

    Warren, S.

    1980-01-01

    The author puts low dose irradiation risks in perspective using average background radiation doses for standards. He assailed irresponsible media coverage during the height of public interest in the Three-Mile Island Reactor incident

  11. Topics on study of low dose-effect relationship

    International Nuclear Information System (INIS)

    Yamada, Takeshi; Ohyama, Harumi

    1999-01-01

    It is not exceptional but usually observed that a dose-effect relationship in biosystem is not linear. Sometimes, the low dose-effect relationship appears entirely contrary to the expectation from high dose-effect. This is called a 'hormesis' phenomena. A high dose irradiation inflicts certainly an injury on biosystem. No matter how low the dose may be, an irradiation might inflict some injury on biosystem according to Linear Non-Threshold hypothesis(LNT). On the contrary to the expectation, a low dose irradiation stimulates immune system, and promotes cell proliferation. This is called 'radiation hormesis'. The studies of the radiation hormesis are made on from four points of view as follows: (1) radiation adaptive response, (2) revitalization caused by a low dose stimulation, (3) a low dose response unexpected from the LNT hypothesis, (4) negation of the LNT hypothesis. The various empirical proofs of radiation hormesis are introduced in the report. (M . Suetake)

  12. Development of Plant Application Technique of Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Byung Yeoup; Kim, Jae Sung; Lim, Yong Taek (and others)

    2007-07-15

    The project was carried out to achieve three aims. First, development of application techniques of cell-stimulating effects by low-dose radiation. Following irradiation with gamma-rays of low doses, beneficial effects in crop germination, early growth, and yield were investigated using various plant species and experimental approaches. For the actual field application, corroborative studies were also carried out with a few concerned experimental stations and farmers. Moreover, we attempted to establish a new technique of cell cultivation for industrial mass-production of shikonin, a medicinal compound from Lithospermum erythrorhizon and thereby suggested new application fields for application techniques of low-dose radiation. Second, elucidation of action mechanisms of ionizing radiation in plants. By investigating changes in plant photosynthesis and physiological metabolism, we attempted to elucidate physiological activity-stimulating effects of low-dose radiation and to search for radiation-adaptive cellular components. Besides, analyses of biochemical and molecular biological mechanisms for stimulus-stimulating effects of low-dose radiation were accomplished by examining genes and proteins inducible by low-dose radiation. Third, development of functional crop plants using radiation-resistant factors. Changes in stress-tolerance of plants against environmental stress factors such as light, temperature, salinity and UV-B stress after exposed to low-dose gamma-rays were investigated. Concerned reactive oxygen species, antioxidative enzymes, and antioxidants were also analyzed to develop high value-added and environment-friendly functional plants using radiation-resistant factors. These researches are important to elucidate biological activities increased by low-dose radiation and help to provide leading technologies for improvement of domestic productivity in agriculture and development of high value-added genetic resources.

  13. Low dose rate Ir-192 interstitial brachytherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oki, Yosuke; Dokiya, Takushi; Yorozu, Atsunori; Suzuki, Takayuki; Saito, Shiro; Monma, Tetsuo; Ohki, Takahiro [National Tokyo Medical Center (Japan); Murai, Masaru; Kubo, Atsushi

    2000-04-01

    From December 1997 through January 1999, fifteen prostatic cancer patients were treated with low dose rate Ir-192 interstitial brachytherapy using TRUS and perineal template guidance without external radiotherapy. Up to now, as no apparent side effects were found, the safety of this treatment is suggested. In the future, in order to treat prostatic cancer patients with interstitial brachytherapy using I-125 or Pd-103, more investigation for this low dose rate Ir-192 interstitial brachytherapy is needed. (author)

  14. Development of Plant Application Technique of Low Dose Radiation

    International Nuclear Information System (INIS)

    Chung, Byung Yeoup; Kim, Jae Sung; Lim, Yong Taek

    2007-07-01

    The project was carried out to achieve three aims. First, development of application techniques of cell-stimulating effects by low-dose radiation. Following irradiation with gamma-rays of low doses, beneficial effects in crop germination, early growth, and yield were investigated using various plant species and experimental approaches. For the actual field application, corroborative studies were also carried out with a few concerned experimental stations and farmers. Moreover, we attempted to establish a new technique of cell cultivation for industrial mass-production of shikonin, a medicinal compound from Lithospermum erythrorhizon and thereby suggested new application fields for application techniques of low-dose radiation. Second, elucidation of action mechanisms of ionizing radiation in plants. By investigating changes in plant photosynthesis and physiological metabolism, we attempted to elucidate physiological activity-stimulating effects of low-dose radiation and to search for radiation-adaptive cellular components. Besides, analyses of biochemical and molecular biological mechanisms for stimulus-stimulating effects of low-dose radiation were accomplished by examining genes and proteins inducible by low-dose radiation. Third, development of functional crop plants using radiation-resistant factors. Changes in stress-tolerance of plants against environmental stress factors such as light, temperature, salinity and UV-B stress after exposed to low-dose gamma-rays were investigated. Concerned reactive oxygen species, antioxidative enzymes, and antioxidants were also analyzed to develop high value-added and environment-friendly functional plants using radiation-resistant factors. These researches are important to elucidate biological activities increased by low-dose radiation and help to provide leading technologies for improvement of domestic productivity in agriculture and development of high value-added genetic resources

  15. Anticonvulsant treatment of sarin-induced seizures with nasal midazolam: An electrographic, behavioral, and histological study in freely moving rats

    International Nuclear Information System (INIS)

    Gilat, E.; Kadar, T.; Levy, A.; Rabinovitz, I.; Cohen, G.; Kapon, Y.; Sahar, R.; Brandeis, R.

    2005-01-01

    Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 ± 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsant effect (53 ± 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted in

  16. Anticonvulsant treatment of sarin-induced seizures with nasal midazolam: An electrographic, behavioral, and histological study in freely moving rats

    Energy Technology Data Exchange (ETDEWEB)

    Gilat, E [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Kadar, T [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Levy, A [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Rabinovitz, I [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Cohen, G [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Kapon, Y [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Sahar, R [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Brandeis, R [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel)

    2005-11-15

    Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 {+-} 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsant effect (53 {+-} 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted

  17. Review of European research trends of low dose radiation risk

    International Nuclear Information System (INIS)

    Iwasaki, Toshiyasu; Yoshida, Kazuo

    2010-01-01

    Large research projects on low dose radiation effects in Europe and US over the past decade have provided limited scientific knowledge which could underpin the validation of radiation protection systems. Recently in Europe, there have been repeated discussions and dialogues to improve the situation, and as the consequence, the circumstances surrounding low dose radiation risks are changing. In 2009, Multidisciplinary European Low Dose Initiative (MELODI) was established as a trans-national organization capable of ensuring appropriate governance of research in the pursuit of a long term shared vision, and Low Dose Research towards Multidisciplinary Integration (DoReMi) network was launched in 2010 to achieve fairly short term results in order to prove the validity of the MELODI approach. It is expected to be very effective and powerful activities to facilitate the reduction of uncertainties in the understanding of low dose risks, but the regulatory requests rushing the reinforcement of radiological protection regulations based on the precautional principles are more increasing. To develop reasonable radiological protection systems based on scientific evidences, we need to accelerate to collect scientific evidences which could directly underpin more appropriate radiation protection systems even in Japan. For the purpose, we Japan need to develop from an independent standpoint and share as a multidisciplinary vision a long term and holistic research strategy which enables to enhance Japanese advantages such as low dose rate facilities and animal facilities, as soon as possible. (author)

  18. Toxicity bioassay in mice exposed to low dose-rate radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joog Sun; Gong, Eun Ji; Heo, Kyu; Yang, Kwang Mo [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of)

    2013-04-15

    The systemic effect of radiation increases in proportion to the dose amount and rate. The association between accumulated radiation dose and adverse effects, which is derived according to continuous low dose-rate radiation exposure, is not clearly elucidated. Our previous study showed that low dose-rate radiation exposure did not cause adverse effects in BALB/c mice at dose levels of ≤2 Gy, but the testis weight decreased at a dose of 2 Gy. In this study, we studied the effects of irradiation at the low dose rate (3.49 mGy/h) in the testes of C57BL/6 mice. Mice exposed to a total dose of 0.02, 0.2, and 2 Gy were found to be healthy and did not show any significant changes in body weight and peripheral blood components. However, mice irradiated with a dose of 2 Gy had significantly decreased testis weight. Further, histological studies and sperm evaluation also demonstrated changes consistent with the findings of decreased testis weight. In fertile patients found to have arrest of sperm maturation, the seminiferous tubules lack the DNMT1 and HDAC1 protein. The decrease of DNMT1 and HDAC1 in irradiated testis may be the part of the mechanism via which low dose-rate irradiation results in teticular injury. In conclusion, despite a low dose-rate radiation, our study found that when mice testis were irradiated with 2 Gy at 3.49 mGy/h dose rate, there was significant testicular and sperm damage with decreased DNMT1 and HDAC1 expression.

  19. Protective Effect of Low Dose Gamma Irradiation against Oxidative Damage in Rats Administrated with Ferric- Nitrilotriacetate

    International Nuclear Information System (INIS)

    Mansonr, S.Z.

    2009-01-01

    Many studies have demonstrated the beneficial adaptive response of low dose gamma-irradiation. Low dose gamma-irradiation (LDR) might be effective for the prevention of various reactive oxygen species-related diseases. Ferric nitrilotriacetate (Fe-NTA) is a strong oxidant, which generates highly reactive hydroxyl radical and causes injuries of various organs including the kidney and liver. This study was designed to investigate the ability of low dose gamma-irradiation to restrain Fe-NT A induced oxidative stress. Sprague Dawley male albino rats were subjected to low dose gamma-irradiation (50 cGy). Animals were challenged with Fe-NT A (9 mg Fe/kg body weight, intraperitoneally). Results showed that Fe-NTA enhances lipid peroxidation (LPx) accompanied with reduction in glutathione (GSH) content, antioxidant enzymes, viz., glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and phase-U metabolizing enzyme glutathione-S-transferase (GST). Fe-NTA also enhances the concentration of blood urea nitrogen (BUN) and serum creatinine as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) activities. Exposure to low dose gamma- irradiation (3 h after Fe-NTA administration) resulted in a significant decrease in LPx, BUN, serum creatinine contents as well as ALT, AST and GGT enzyme activities. GSH content; GST and antioxidant enzymes were also recovered to significant level. Thus, our data suggest that exposure to LDR might be a useful antioxidant mediator to suppress the Fe-NTA induced-oxidative damage in rats

  20. Protective Effect of Low Dose Gamma Irradiation against Oxidative Damage in Rats Administrated with Ferric- Nitrilotriacetate

    International Nuclear Information System (INIS)

    Mansonr, S.Z.

    2008-01-01

    Many studies have demonstrated the beneficial adaptive response of low dose gamma-irradiation. Low dose gamma-irradiation (LDR) might be effective for the prevention of various reactive oxygen species-related diseases. Ferric nitrilotriacetate (Fe-NTA) is a strong oxidant, which generates highly reactive hydroxyl radical and causes injuries of various organs including the kidney and liver. This study was designed to investigate the ability of low dose gamma-irradiation to restrain Fe-NT A induced oxidative stress. Sprague Dawley male albino rats were subjected to low dose gamma-irradiation (50 cGy). Animals were challenged with Fe-NT A (9 mg Fe/kg body weight, intraperitoneally). Results showed that Fe-NTA enhances lipid peroxidation (LPx) accompanied with reduction in glutathione (GSH) content, antioxidant enzymes, viz., glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and phase-U metabolizing enzyme glutathione-S-transferase (GST). Fe-NTA also enhances the concentration of blood urea nitrogen (BUN) and serum creatinine as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) activities. Exposure to low dose gamma- irradiation (3 h after Fe-NTA administration) resulted in a significant decrease in LPx, BUN, serum creatinine contents as well as ALT, AST and GGT enzyme activities. GSH content; GST and antioxidant enzymes were also recovered to significant level. Thus, our data suggest that exposure to LDR might be a useful antioxidant mediator to suppress the Fe-NTA induced-oxidative damage in rats

  1. Review and Evaluation of Updated Research on the Health Effects Associated with Low-Dose Ionizing Radiation

    International Nuclear Information System (INIS)

    Dauer, Lawrence T.; Brooks, Antone L.; Hoel, David G.; Morgan, William F.; Stram, Daniel; Tran, Phung

    2010-01-01

    Potential health effects of low levels of radiation have predominantly been based on those effects observed at high levels of radiation. The authors have reviewed more than 200 percent publications in radiobiology and epidermiology related to low dose radiation and concluded that recent radiobiological studies at low-doses; that doses <100 mSv in a single exposure appear to be too small to allow epidermiological detection of statistically significant excess cancers in the presence of naturally occurring cancers; that low dose radiation research should to holistic, systems-based approaches to develop models that define the shape of the dose-response relationships at low doses; and that these results should be combined with the latest epidermiology to produce a comprehensive understanding of radiation effects that addresses both damage, likely with a linear effect, and response, possibly with non-linear consequences.

  2. Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

    International Nuclear Information System (INIS)

    Nomura, Takaharu

    2008-01-01

    Living organisms have developed complex biological system which protects themselves against environmental radiation, and irradiation with proper dose, dose-rate and irradiation time can stimulate their biological responses against oxidative stress evoked by the irradiation. Because reactive oxygen species are involved in various human diseases, non-toxic low dose/low dose-rate radiation can be utilized for the amelioration of such diseases. In this study, we used mouse experimental models for fatty liver, nephritis, diabetes, and ageing to elucidate the ameliorative effect of low dose/low dose-rate radiation in relation to endogenous antioxidant activity. Single irradiation at 0.5 Gy ameliorates carbon tetrachloride-induced fatty liver. The irradiation increases hepatic anti-oxidative system involving glutathione and glutathione peroxidase, suggesting that endogenous radical scavenger is essential for the ameliorative effect of low dose radiation on carbon tetrachloride-induced fatty liver. Single irradiation at 0.5 Gy ameliorates ferric nitrilotriacetate-induced nephritis. The irradiation increases catalase and decreases superoxide dismutase in kidney. The result suggests that low dose radiation reduced generation of hydroxide radical generation by reducing cellular hydroperoxide level. Single irradiation at 0.5 Gy at 12 week of age ameliorates incidence of type I diabetes in non-obese diabetic (NOD) mice through the suppression of inflammatory activity of splenocytes, and resultant apoptosis of β-cells in pancreas. The irradiation activities of superoxide dismutase and catalase, which coordinately diminish intracellular reactive oxygen species. Continuous irradiation at 0.70 mGy/hr from 10 week of age elongates life span, and suppresses alopecia in type II diabetesmice. The irradiation improved glucose clearance without affecting insulin-resistance, and increased pancreatic catalase activity. The results suggest that continuous low dose-rate irradiation protect

  3. Bioassay in BALB/c mice exposed to low dose rate radiation

    Energy Technology Data Exchange (ETDEWEB)

    Km, Sung Dae; Gong, Eun Ji; Bae, Min Ji; Yang, Kwang Mo; Kim, Joong Sun [Dongnam Institute of Radiological and Medical Sciences, Suwon (Korea, Republic of)

    2012-09-15

    The present study was performed to investigate the toxicity of low-dose-rate irradiation in BALB/c mice. Twenty mice of each sex were randomly assigned to four groups of five mice each and were exposed to 0 (sham), 0.02, 0.2, or 2 Gy, equivalents to low-dose-rate irradiation to 3.49 mGy{center_dot}h{sup -1}. Urine, blood, and blood biochemistry were analyzed, and organ weight was measured. The low-dose-rate irradiation did not induce any toxicologically significant changes in mortality, clinical signs, body weight, food and water consumption, urinalysis, and serum biochemistry. However, the weights of reproductive organs including the testis, ovary, and uterus decreased in a dose-dependent manner. Irradiation at 2 Gy significantly decreased the testis, ovary, and uterus weights, but did not change the weights of other organs. There were no adverse effects on hematology in any irradiated group and only the number of neutrophils increased dose dependently. The low-dose-rate irradiation exposure did not cause adverse effects in mice at dose levels of 2 Gy or less, but the reproductive systems of male and female mice showed toxic effects.

  4. Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

    Science.gov (United States)

    Kopp, Felix K; Holzapfel, Konstantin; Baum, Thomas; Nasirudin, Radin A; Mei, Kai; Garcia, Eduardo G; Burgkart, Rainer; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B

    2016-01-01

    We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

  5. Optimised low-dose multidetector CT protocol for children with cranial deformity

    Energy Technology Data Exchange (ETDEWEB)

    Vazquez, Jose Luis [Complejo Hospitalario Universitario de Vigo, Department of Radiology, Vigo, Pontevedra (Spain); Pombar, Miguel Angel [Complejo Hospitalario Universitario de Santiago, Department of Radiophysics, Santiago de Compostela, La Coruna (Spain); Pumar, Jose Manuel [Complejo Hospitalario Universitario de Santiago, Department of Radiology, Santiago de Compostela, La Coruna (Spain); Campo, Victor Miguel del [Complejo Hospitalario Universitario de Vigo, Department of Public Health, Vigo, Pontevedra (Spain)

    2013-08-15

    To present an optimised low-dose multidetector computed tomography (MDCT) protocol for the study of children with cranial deformity. Ninety-one consecutive MDCT studies were performed in 80 children. Studies were performed with either our standard head CT protocol (group 1, n = 20) or a low-dose cranial deformity protocol (groups 2 and 3). Group 2 (n = 38), initial, and group 3 (n = 33), final and more optimised. All studies were performed in the same 64-MDCT equipment. Cranial deformity protocol was gradationally optimised decreasing kVp, limiting mA range, using automatic exposure control (AEC) and increasing the noise index (NI). Image quality was assessed. Dose indicators such us CT dose index volume (CTDIvol), dose-length product (DLP) and effective dose (E) were used. The optimised low-dose protocol reached the following values: 80 kVp, mA range: 50-150 and NI = 23. We achieved a maximum dose reduction of 10-22 times in the 1- to 12-month-old cranium in regard to the 2004 European guidelines for MDCT. A low-dose MDCT protocol that may be used as the first diagnostic imaging option in clinically selected patients with skull abnormalities. (orig.)

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

    OpenAIRE

    El-Shanshoury, H.; El-Shanshoury, G.; Abaza, A.

    2016-01-01

    Exposure to ionizing radiation is known to have lethal effects in blood cells. It is predicted that an individual may spend days, weeks or even months in a radiation field without becoming alarmed. The study aimed to discuss the evaluation of low dose ionizing radiation (IR) effect on some blood components in animal model. Hematological parameters were determined for 110 animal rats (divided into 8 groups) pre- and post-irradiation. An attempt to explain the blood changes resulting from both ...

  7. Low-dose radiation epidemiological studies: an assessment of methodological problems

    International Nuclear Information System (INIS)

    Modan, B.

    1991-01-01

    The present report attempts to assess the problems inherent in the analysis of low dose radiation studies, with emphasis on possible sources of methodological errors in the published data, and the consequent relevance to risk estimates. The published data examined concerned populations exposed to nuclear sources such as fallout, weapons' test or in the vicinity of nuclear reactors, occupational exposure, intra-uterine diagnostic X-rays, scattered radiation following X-ray therapy and background irradiation. (UK)

  8. Biological effect of low-dose application beta-radiation on the gingival mucosa of dogs

    International Nuclear Information System (INIS)

    Ippolitov, Yu.A.; Kovtun, N.N.; Timofeev, L.V.

    1999-01-01

    Biological effect of low-dose application beta-radiation on the gingival mucosa of dogs is studied. Obtained data illustrate the interactions between tissues in local exposure of live tissue to beta-radiation and determine the threshold total dose as 400 sGy. Higher doses lead to secondary changes in the gingival mucosa after which the tissue barrier does not recover [ru

  9. The oxime pro-2-PAM provides minimal protection against the CNS effects of the nerve agents sarin, cyclosarin, and VX in guinea pigs.

    Science.gov (United States)

    Shih, Tsung-Ming; Guarisco, John A; Myers, Todd M; Kan, Robert K; McDonough, John H

    2011-01-01

    This study examined whether pro-2-PAM, a pro-drug dihydropyridine derivative of the oxime 2-pralidoxime (2-PAM) that can penetrate the brain, could prevent or reverse the central toxic effects of three nerve agents; sarin, cyclosarin, and VX. The first experiment tested whether pro-2-PAM could reactivate guinea pig cholinesterase (ChE) in vivo in central and peripheral tissues inhibited by these nerve agents. Pro-2-PAM produced a dose-dependent reactivation of sarin- or VX-inhibited ChE in both peripheral and brain tissues, but with substantially greater reactivation in peripheral tissues compared to brain. Pro-2-PAM produced 9-25% reactivation of cyclosarin-inhibited ChE in blood, heart, and spinal cord, but no reactivation in brain or muscle tissues. In a second experiment, the ability of pro-2-PAM to block or terminate nerve agent-induced electroencephalographic seizure activity was evaluated. Pro-2-PAM was able to block sarin- or VX-induced seizures (16-33%) over a dose range of 24-32 mg/kg, but was ineffective against cyclosarin-induced seizures. Animals that were protected from seizures showed significantly less weight loss and greater behavioral function 24 h after exposure than those animals that were not protected. Additionally, brains were free from neuropathology when pro-2-PAM prevented seizures. In summary, pro-2-PAM provided modest reactivation of sarin- and VX-inhibited ChE in the brain and periphery, which was reflected by a limited ability to block or terminate seizures elicited by these agents. Pro-2-PAM was able to reactivate blood, heart, and spinal cord ChE inhibited by cyclosarin, but was not effective against cyclosarin-induced seizures.

  10. Effect of low-dose irradiation on pregnant mouse haemopoiesis

    International Nuclear Information System (INIS)

    Weinberg, S.R.; McCarthy, E.G.; MacVittie, T.J.; Baum, S.J.

    1981-01-01

    The effects of low-dose gamma radiation to haemopoietic progenitor cell compartments of the marrow and spleen of virgin female mice and pregnant mice were studied. Microplasma clot cultures were used to assess burst-forming uniterythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) activity, and double-layer agar cultures were established to evaluate granulocyte-macrophage colony-forming cell (GM-CFC) and macrophage colony-forming cell (M-CFC). The apparent shift in maternal erythropoiesis from the bone marrow to the enlarged spleen was reflected by an increase in CFU-E and BFU-E per spleen and a concomitant decrease in CFU-E and BFU-E per femur. Whereas maternal GM-CFC values per femur increased 36%, maternal GM-CFC per spleen increased by 172% compared to virgin values. Total-body irradiation to the day-10.5 pregnant mouse caused a further suppression of day-14.5 medullary erythropoiesis (i.e. decreased CFU-E values) compared to the virgin female mouse. An ability of the maternal spleen to support further compensatory erythropoiesis following increasing doses of radiation was demonstrated. Four days after 1.0 Gy exposure, maternal values for GM-CFC per femur or spleen decreased to nonirradiated virgin mice values. M-CFC per maternal femur decreased to nonirradiated virgin mice values. M-CFC per maternal femur decreased following 1.5 Gy, but M-CFC per spleen appeared to be unaffected with doses from 0.5 to 2.0 Gy. (author)

  11. Low Dose Suppression of Neoplastic Transformation in Vitro

    Energy Technology Data Exchange (ETDEWEB)

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  12. Effects of low dose radiation on tumor-bearing mice

    International Nuclear Information System (INIS)

    Feng Li; Hou Dianjun; Huang Shanying; Deng Daping; Wang Linchao; Cheng Yufeng

    2007-01-01

    Objective: To explore the effects of low-dose radiation on tumor-bearing mice and radiotherapy induced by low-dose radiation. Methods: Male Wistar mice were implanted with Walker-256 sarcoma cells in the right armpit. On day 4, the mice were given 75 mGy whole-body X-ray radiation. From the fifth day, tumor volume was measured, allowing for the creation of a graph depicting tumor growth. Lymphocytes activity in mice after whole-body X-ray radiation with LDR was determinned by FCM. Cytokines level were also determined by ELISA. Results: Compared with the radiotherapy group, tumor growth was significantly slower in the mice pre-exposed to low-dose radiation (P<0.05), after 15 days, the average tumor weight in the mice pre- exposed to low-dose radiation was also significantly lower (P<0.05). Lymphocytes activity and the expression of the CK in mice after whole-body y-ray radiation with LDR increased significantly. Conclusions: Low-dose radiation can markedly improve the immune function of the lymphocyte, inhibit the tumor growth, increase the resistant of the high-dose radiotherapy and enhance the effect of radiotherapy. (authors)

  13. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-01-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

  14. Donor-specific cell-based assays in studying sensitivity to low-dose radiation: a population-based perspective

    Directory of Open Access Journals (Sweden)

    Dora eIl'yasova

    2014-11-01

    Full Text Available Currently, a linear no-threshold model is used to estimate health risks associated with exposure to low-dose radiation, a prevalent exposure in the general population, because the direct estimation from epidemiological studies suffers from uncertainty. This model has been criticized based on unique biology of low-dose radiation. Whether the departure from linearity is toward increased or decreased risk is intensely debated. We present an approach based on individual radiosensitivity testing and discuss how individual radiosensitivity can be assessed with the goal to develop a quantifiable measure of cellular response that can be conducted via high-throughput population testing.

  15. Risks to health from radiation at low dose rates

    International Nuclear Information System (INIS)

    Gentner, N.E.; Osborne, R.V.

    1997-01-01

    Our focus is on whether, using a balance-of-evidence approach, it is possible to say that at a low enough dose, or at a sufficiently low dose rate, radiation risk reduces to zero in a population. We conclude that insufficient evidence exists at present to support such a conclusion. In part this reflects statistical limitations at low doses, and in part (although mechanisms unquestionably exist to protect us against much of the damage induced by ionizing radiation) the biological heterogeneity of human populations, which means these mechanisms do not act in all members of the population at all times. If it is going to be possible to demonstrate that low doses are less dangerous than we presently assume, the evidence, paradoxically, will likely come from studies of higher dose and dose rate scenarios than are encountered occupationally. (author)

  16. Regulatory aspects of low doses control in Albania

    International Nuclear Information System (INIS)

    Dollani, K.; Kushe, R.

    1997-01-01

    In the present paper are described the status of regulatory aspects of low doses control as well as the existing procedures for their implementation in Albania. According to new Radiological Protection Act, approved by Parliament in 1995, the establishment of the infrastructures in radiation protection area is in course, accompanied by the installation and functioning of new equipment for low dose control. Based in many years experience it is concluded that personal doses of the workers added by practices in Albania are 1/10 of dose Emits. Some particular cases of overexposured workers were investigated. Last times the elements of the optimisation procedures (QA and QC) are outlined in the frame of improving regulatory aspects of low doses control. (author)

  17. Intraoperative use of low-dose recombinant activated factor VII during thoracic aortic operations.

    Science.gov (United States)

    Andersen, Nicholas D; Bhattacharya, Syamal D; Williams, Judson B; Fosbol, Emil L; Lockhart, Evelyn L; Patel, Mayur B; Gaca, Jeffrey G; Welsby, Ian J; Hughes, G Chad

    2012-06-01

    Numerous studies have supported the effectiveness of recombinant activated factor VII (rFVIIa) for the control of bleeding after cardiac procedures; however safety concerns persist. Here we report the novel use of intraoperative low-dose rFVIIa in thoracic aortic operations, a strategy intended to improve safety by minimizing rFVIIa exposure. Between July 2005 and December 2010, 425 consecutive patients at a single referral center underwent thoracic aortic operations with cardiopulmonary bypass (CPB); 77 of these patients received intraoperative low-dose rFVIIa (≤60 μg/kg) for severe coagulopathy after CPB. Propensity matching produced a cohort of 88 patients (44 received intraoperative low-dose rFVIIa and 44 controls) for comparison. Matched patients receiving intraoperative low-dose rFVIIa got an initial median dose of 32 μg/kg (interquartile range [IQR], 16-43 μg/kg) rFVIIa given 51 minutes (42-67 minutes) after separation from CPB. Patients receiving intraoperative low-dose rFVIIa demonstrated improved postoperative coagulation measurements (partial thromboplastin time 28.6 versus 31.5 seconds; p=0.05; international normalized ratio, 0.8 versus 1.2; pproduct transfusions (2.5 versus 5.0 units; p=0.05) compared with control patients. No patient receiving intraoperative low-dose rFVIIa required postoperative rFVIIa administration or reexploration for bleeding. Rates of stroke, thromboembolism, myocardial infarction, and other adverse events were equivalent between groups. Intraoperative low-dose rFVIIa led to improved postoperative hemostasis with no apparent increase in adverse events. Intraoperative rFVIIa administration in appropriately selected patients may correct coagulopathy early in the course of refractory blood loss and lead to improved safety through the use of smaller rFVIIa doses. Appropriately powered randomized studies are necessary to confirm the safety and efficacy of this approach. Copyright © 2012 The Society of Thoracic Surgeons

  18. Effects of low dose radiation and epigenetic regulation

    International Nuclear Information System (INIS)

    Jiao Benzheng; Ma Shumei; Yi Heqing; Kong Dejuan; Zhao Guangtong; Gao Lin; Liu Xiaodong

    2010-01-01

    Purpose: To conclude the relationship between epigenetics regulation and radiation responses, especially in low-dose area. Methods: The literature was examined for papers related to the topics of DNA methylation, histone modifications, chromatin remodeling and non-coding RNA modulation in low-dose radiation responses. Results: DNA methylation and radiation can regulate reciprocally, especially in low-dose radiation responses. The relationship between histone methylation and radiation mainly exists in the high-dose radiation area; histone deacetylase (HDAC) inhibitors show a promising application to enhance radiation sensitivity, no matter whether in low-dose or high-dose areas; the connection between γ-H2AX and LDR has been remained unknown, although γ-H2AX has been shown no radiation sensitivities with 1-15 Gy irradiation; histone ubiquitination play an important role in DNA damage repair mechanism. Moreover, chromatin remodeling has an integral role in DSB repair and the chromatin response, in general, may be precede DNA end resection. Finally, the effect of radiation on miRNA expression seems to vary according to cell type, radiation dose, and post-irradiation time point. Conclusion: Although the advance of epigenetic regulation on radiation responses, which we are managing to elucidate in this review, has been concluded, there are many questions and blind blots deserved to investigated, especially in low-dose radiation area. However, as progress on epigenetics, we believe that many new elements will be identified in the low-dose radiation responses which may put new sights into the mechanisms of radiation responses and radiotherapy. (authors)

  19. Low-dose vaporized cannabis significantly improves neuropathic pain.

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-02-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant