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Sample records for chronic low-dose radiation

  1. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  2. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    PubMed Central

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation. PMID:26795421

  3. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    SciTech Connect

    Shin, Suk Chul; Lee, Kyung-Mi; Kang, Yu Mi; Kim, Kwanghee; Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo; Kim, Chong Soon; Kim, Hee Sun

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  4. Injury to the blood-testis barrier after low-dose-rate chronic radiation exposure in mice.

    PubMed

    Son, Y; Heo, K; Bae, M J; Lee, C G; Cho, W S; Kim, S D; Yang, K; Shin, I S; Lee, M Y; Kim, J S

    2015-11-01

    Exposure to ionising radiation induces male infertility, accompanied by increasing permeability of the blood-testis barrier. However, the effect on male fertility by low-dose-rate chronic radiation has not been investigated. In this study, the effects of low-dose-rate chronic radiation on male mice were investigated by measuring the levels of tight-junction-associated proteins (ZO-1 and occludin-1), Niemann-Pick disease type 2 protein (NPC-2) and antisperm antibody (AsAb) in serum. BALB/c mice were exposed to low-dose-rate radiation (3.49 mGy h(-1)) for total exposures of 0.02 (6 h), 0.17 (2 d) and 1.7 Gy (21 d). Based on histological examination, the diameter and epithelial depth of seminiferous tubules were significantly decreased in 1.7-Gy-irradiated mice. Compared with those of the non-irradiated group, 1.7-Gy-irradiated mice showed significantly decreased ZO-1, occludin-1 and NPC-2 protein levels, accompanied with increased serum AsAb levels. These results suggest potential blood-testis barrier injury and immune infertility in male mice exposed to low-dose-rate chronic radiation.

  5. [Radiation situation prognosis for deep space: reactions of water and living systems to chronic low-dose ionizing irradiation].

    PubMed

    Ushakov, I B; Tsetlin, V V; Moisa, S S

    2013-01-01

    The authors review the findings of researches into the effects of low-dose ionizing irradiation on diverse biological objects (embryonic Japanese quails, Aspergillus niger, Spirostomum ambiguum Ehrbg., mesenchymal stem cells from mouse marrow, dry higher plants seeds, blood lymphocytes from pilots and cosmonauts). Model experiments with chronic exposure to ionizing radiation doses comparable with the measurements inside orbital vehicles and estimations for trips through the interplanetary space resulted in morphological disorders (embryonic Japanese quails, Aspergillus niger), radiation hormesis (Aspergillus niger, MSCs from mouse marrow), increase in the seed germination rate, inhibition of Spirostomum spontaneous activity, DNA damages, chromosomal aberrations, and increase of the blood lymphocytes reactivity to additional radiation loading. These facts give grounds to assume that the crucial factor in the radiation outcomes is changes in liquid medium. In other words, during extended orbiting within the magnetosphere region and interplanetary missions ionizing radiation affects primarily liquids of organism and, secondarily, its morphofunctional structures. PMID:23700619

  6. [Radiation situation prognosis for deep space: reactions of water and living systems to chronic low-dose ionizing irradiation].

    PubMed

    Ushakov, I B; Tsetlin, V V; Moisa, S S

    2013-01-01

    The authors review the findings of researches into the effects of low-dose ionizing irradiation on diverse biological objects (embryonic Japanese quails, Aspergillus niger, Spirostomum ambiguum Ehrbg., mesenchymal stem cells from mouse marrow, dry higher plants seeds, blood lymphocytes from pilots and cosmonauts). Model experiments with chronic exposure to ionizing radiation doses comparable with the measurements inside orbital vehicles and estimations for trips through the interplanetary space resulted in morphological disorders (embryonic Japanese quails, Aspergillus niger), radiation hormesis (Aspergillus niger, MSCs from mouse marrow), increase in the seed germination rate, inhibition of Spirostomum spontaneous activity, DNA damages, chromosomal aberrations, and increase of the blood lymphocytes reactivity to additional radiation loading. These facts give grounds to assume that the crucial factor in the radiation outcomes is changes in liquid medium. In other words, during extended orbiting within the magnetosphere region and interplanetary missions ionizing radiation affects primarily liquids of organism and, secondarily, its morphofunctional structures.

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

    PubMed Central

    2012-01-01

    Background 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. Results 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). Conclusions 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. PMID:22540409

  8. Radiation Leukemogenesis at Low Dose Rates

    SciTech Connect

    Weil, Michael; Ullrich, Robert

    2013-09-25

    The major goals of this program were to study the efficacy of low dose rate radiation exposures for the induction of acute myeloid leukemia (AML) and to characterize the leukemias that are caused by radiation exposures at low dose rate. An irradiator facility was designed and constructed that allows large numbers of mice to be irradiated at low dose rates for protracted periods (up to their life span). To the best of our knowledge this facility is unique in the US and it was subsequently used to study radioprotectors being developed for radiological defense (PLoS One. 7(3), e33044, 2012) and is currently being used to study the role of genetic background in susceptibility to radiation-induced lung cancer. One result of the irradiation was expected; low dose rate exposures are ineffective in inducing AML. However, another result was completely unexpected; the irradiated mice had a very high incidence of hepatocellular carcinoma (HCC), approximately 50%. It was unexpected because acute exposures are ineffective in increasing HCC incidence above background. This is a potential important finding for setting exposure limits because it supports the concept of an 'inverse dose rate effect' for some tumor types. That is, for the development of some tumor types low dose rate exposures carry greater risks than acute exposures.

  9. Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation.

    PubMed

    Flegal, Matthew; Blimkie, Melinda S; Wyatt, Heather; Bugden, Michelle; Surette, Joel; Klokov, Dmitry

    2015-01-01

    Low dose radiation exposure may produce a variety of biological effects that are different in quantity and quality from the effects produced by high radiation doses. Addressing questions related to environmental, occupational and public health safety in a proper and scientifically justified manner heavily relies on the ability to accurately measure the biological effects of low dose pollutants, such as ionizing radiation and chemical substances. DNA damage and repair are the most important early indicators of health risks due to their potential long term consequences, such as cancer. Here we describe a protocol to study the effect of chronic in vivo exposure to low doses of γ- and β-radiation on DNA damage and repair in mouse spleen cells. Using a commonly accepted marker of DNA double-strand breaks, phosphorylated histone H2AX called γH2AX, we demonstrate how it can be used to evaluate not only the levels of DNA damage, but also changes in the DNA repair capacity potentially produced by low dose in vivo exposures. Flow cytometry allows fast, accurate and reliable measurement of immunofluorescently labeled γH2AX in a large number of samples. DNA double-strand break repair can be evaluated by exposing extracted splenocytes to a challenging dose of 2 Gy to produce a sufficient number of DNA breaks to trigger repair and by measuring the induced (1 hr post-irradiation) and residual DNA damage (24 hrs post-irradiation). Residual DNA damage would be indicative of incomplete repair and the risk of long-term genomic instability and cancer. Combined with other assays and end-points that can easily be measured in such in vivo studies (e.g., chromosomal aberrations, micronuclei frequencies in bone marrow reticulocytes, gene expression, etc.), this approach allows an accurate and contextual evaluation of the biological effects of low level stressors. PMID:26168333

  10. Epigenomic Adaptation to Low Dose Radiation

    SciTech Connect

    Gould, Michael N.

    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.’

  11. Low-dose radiation exposure and carcinogenesis.

    PubMed

    Suzuki, Keiji; Yamashita, Shunichi

    2012-07-01

    Absorption of energy from ionizing radiation by the genetic material in the cell leads to damage to DNA, which in turn leads to cell death, chromosome aberrations and gene mutations. While early or deterministic effects result from organ and tissue damage caused by cell killing, latter two are considered to be involved in the initial events that lead to the development of cancer. Epidemiological studies have demonstrated the dose-response relationships for cancer induction and quantitative evaluations of cancer risk following exposure to moderate to high doses of low-linear energy transfer radiation. A linear, no-threshold model has been applied to assessment of the risks resulting from exposure to moderate and high doses of ionizing radiation; however, a statistically significant increase has hardly been described for radiation doses below 100 mSv. This review summarizes our current knowledge of the physical and biological features of low-dose radiation and discusses the possibilities of induction of cancer by low-dose radiation. PMID:22641644

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

    PubMed

    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. PMID:26113293

  13. Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay.

    PubMed

    Kumar, P R Vivek; Seshadri, M; Jaikrishan, G; Das, Birajalaxmi

    2015-05-01

    This study investigates whether peripheral blood mononuclear cells (PBMCs) from inhabitants of Kerala in southwest India, exposed to chronic low dose natural radiation in vivo (>1 mSv year(-1)), respond with a radioadaptive response to a challenging dose of gamma radiation. Toward this goal, PBMCs isolated from 77 subjects from high-level natural radiation areas (HLNRA) and 37 subjects from a nearby normal level natural radiation area (NLNRA) were challenged with 2 Gy and 4 Gy gamma radiation. Subjects from HLNRA were classified based on the mean annual effective dose received, into low dose group (LDG) and high dose group (HDG) with mean annual effective doses of 2.69 mSv (N=43, range 1.07 mSv year(-1) to 5.55 mSv year(-1)) and 9.62 mSv (N = 34, range 6.07 mSv year(-1) to 17.41 mSv year(-1)), respectively. DNA strand breaks and repair kinetics (at 7 min, 15 min and 30 min after 4 Gy) were evaluated using the alkaline single cell gel electrophoresis (comet) assay. Initial levels of DNA strand breaks observed after either a 2 Gy or a 4 Gy challenging dose were significantly lower in subjects of the HDG from HLNRA compared to subjects of NLNRA (2 Gy, P = 0.01; 4 Gy, P = 0.02) and LDG (2 Gy P = 0.01; 4 Gy, P=0.05). Subjects of HDG from HLNRA showed enhanced rejoining of DNA strand breaks (HDG/NLNRA, P = 0.06) during the early stage of repair (within 7 min). However at later times a similar rate of rejoining of strand breaks was observed across the groups (HDG, LDG and NLNRA). Preliminary results from our study suggest in vivo chronic low-level natural radiation provides an initial exposure that allows an adaptation to a subsequent higher radiation exposure, perhaps through improving DNA repair via an unknown mechanism. Therefore, further investigations would be necessary in this population to understand the biological and health effects of chronic low-level natural radiation exposures.

  14. Fukushima simulation experiment: assessing the effects of chronic low-dose-rate internal 137Cs radiation exposure on litter size, sex ratio, and biokinetics in mice.

    PubMed

    Nakajima, Hiroo; Yamaguchi, Yoshiaki; Yoshimura, Takashi; Fukumoto, Manabu; Todo, Takeshi

    2015-12-01

    To investigate the transgenerational effects of chronic low-dose-rate internal radiation exposure after the Fukushima Daiichi Nuclear Power Plant accident in Japan, 18 generations of mice were maintained in a radioisotope facility, with free access to drinking water containing (137)CsCl (0 and 100 Bq/ml). The (137)Cs distribution in the organs of the mice was measured after long-term ad libitum intake of the (137)CsCl water. The litter size and the sex ratio of the group ingesting the (137)Cs water were compared with those of the control group, for all 18 generations of mice. No significant difference was noted in the litter size or the sex ratio between the mice in the control group and those in the group ingesting the (137)Cs water. The fixed internal exposure doses were ∼160 Bq/g and 80 Bq/g in the muscles and other organs, respectively. PMID:26825299

  15. Fukushima simulation experiment: assessing the effects of chronic low-dose-rate internal 137Cs radiation exposure on litter size, sex ratio, and biokinetics in mice

    PubMed Central

    Nakajima, Hiroo; Yamaguchi, Yoshiaki; Yoshimura, Takashi; Fukumoto, Manabu; Todo, Takeshi

    2015-01-01

    To investigate the transgenerational effects of chronic low-dose-rate internal radiation exposure after the Fukushima Daiichi Nuclear Power Plant accident in Japan, 18 generations of mice were maintained in a radioisotope facility, with free access to drinking water containing 137CsCl (0 and 100 Bq/ml). The 137Cs distribution in the organs of the mice was measured after long-term ad libitum intake of the 137CsCl water. The litter size and the sex ratio of the group ingesting the 137Cs water were compared with those of the control group, for all 18 generations of mice. No significant difference was noted in the litter size or the sex ratio between the mice in the control group and those in the group ingesting the 137Cs water. The fixed internal exposure doses were ∼160 Bq/g and 80 Bq/g in the muscles and other organs, respectively. PMID:26825299

  16. A New Era of Low-Dose Radiation Epidemiology.

    PubMed

    Kitahara, Cari M; Linet, Martha S; Rajaraman, Preetha; Ntowe, Estelle; Berrington de González, Amy

    2015-09-01

    The last decade has introduced a new era of epidemiologic studies of low-dose radiation facilitated by electronic record linkage and pooling of cohorts that allow for more direct and powerful assessments of cancer and other stochastic effects at doses below 100 mGy. Such studies have provided additional evidence regarding the risks of cancer, particularly leukemia, associated with lower-dose radiation exposures from medical, environmental, and occupational radiation sources, and have questioned the previous findings with regard to possible thresholds for cardiovascular disease and cataracts. Integrated analysis of next generation genomic and epigenetic sequencing of germline and somatic tissues could soon propel our understanding further regarding disease risk thresholds, radiosensitivity of population subgroups and individuals, and the mechanisms of radiation carcinogenesis. These advances in low-dose radiation epidemiology are critical to our understanding of chronic disease risks from the burgeoning use of newer and emerging medical imaging technologies, and the continued potential threat of nuclear power plant accidents or other radiological emergencies. PMID:26231501

  17. Response of Biological Systems to Low Doses of Ionizing Radiation.

    PubMed

    Hei, Tom K

    2016-03-01

    Radiation is ubiquitous in the environment. Biological effects of exposure to low doses of ionizing radiation are subjected to several modulating factors. Two of these, bystander response and adaptive protections, are discussed briefly. PMID:26808883

  18. Risk of cancer subsequent to low-dose radiation

    SciTech Connect

    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. (PCS)

  19. Low-dose radiation epidemiology studies: status and issues.

    PubMed

    Shore, Roy E

    2009-11-01

    Although the Japanese atomic bomb study and radiotherapy studies have clearly documented cancer risks from high-dose radiation exposures, radiation risk assessment groups have long recognized that protracted or low exposures to low-linear energy transfer radiations are key radiation protection concerns because these are far more common than high-exposure scenarios. Epidemiologic studies of human populations with low-dose or low dose-rate exposures are one approach to addressing those concerns. A number of large studies of radiation workers (Chernobyl clean-up workers, U.S. and Chinese radiological technologists, and the 15-country worker study) or of persons exposed to environmental radiation at moderate to low levels (residents near Techa River, Semipalatinsk, Chernobyl, or nuclear facilities) have been conducted. A variety of studies of medical radiation exposures (multiple-fluoroscopy, diagnostic (131)I, scatter radiation doses from radiotherapy, etc.) also are of interest. Key results from these studies are summarized and compared with risk estimates from the Japanese atomic bomb study. Ideally, one would like the low-dose and low dose-rate studies to guide radiation risk estimation regarding the shape of the dose-response curve, DDREF (dose and dose-rate effectiveness factor), and risk at low doses. However, the degree to which low-dose studies can do so is subject to various limitations, especially those pertaining to dosimetric uncertainties and limited statistical power. The identification of individuals who are particularly susceptible to radiation cancer induction also is of high interest in terms of occupational and medical radiation protection. Several examples of studies of radiation-related cancer susceptibility are discussed, but none thus far have clearly identified radiation-susceptible genotypes.

  20. Low-dose radiation epidemiology studies: status and issues.

    PubMed

    Shore, Roy E

    2009-11-01

    Although the Japanese atomic bomb study and radiotherapy studies have clearly documented cancer risks from high-dose radiation exposures, radiation risk assessment groups have long recognized that protracted or low exposures to low-linear energy transfer radiations are key radiation protection concerns because these are far more common than high-exposure scenarios. Epidemiologic studies of human populations with low-dose or low dose-rate exposures are one approach to addressing those concerns. A number of large studies of radiation workers (Chernobyl clean-up workers, U.S. and Chinese radiological technologists, and the 15-country worker study) or of persons exposed to environmental radiation at moderate to low levels (residents near Techa River, Semipalatinsk, Chernobyl, or nuclear facilities) have been conducted. A variety of studies of medical radiation exposures (multiple-fluoroscopy, diagnostic (131)I, scatter radiation doses from radiotherapy, etc.) also are of interest. Key results from these studies are summarized and compared with risk estimates from the Japanese atomic bomb study. Ideally, one would like the low-dose and low dose-rate studies to guide radiation risk estimation regarding the shape of the dose-response curve, DDREF (dose and dose-rate effectiveness factor), and risk at low doses. However, the degree to which low-dose studies can do so is subject to various limitations, especially those pertaining to dosimetric uncertainties and limited statistical power. The identification of individuals who are particularly susceptible to radiation cancer induction also is of high interest in terms of occupational and medical radiation protection. Several examples of studies of radiation-related cancer susceptibility are discussed, but none thus far have clearly identified radiation-susceptible genotypes. PMID:19820457

  1. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    EPA Science Inventory

    Carcinogenic Effects of Low Doses of Ionizing Radiation

    R Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

    The form of the dose-response curve for radiation-induced cancers, particu...

  2. Malignant melanoma of the tongue following low-dose radiation

    SciTech Connect

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

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

    SciTech Connect

    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.

  4. Biological-Based Modeling of Low Dose Radiation Risks

    SciTech Connect

    Scott, Bobby R., Ph.D.

    2006-11-08

    The objective of this project was to refine a biological-based model (called NEOTRANS2) for low-dose, radiation-induced stochastic effects taking into consideration newly available data, including data on bystander effects (deleterious and protective). The initial refinement led to our NEOTRANS3 model which has undergone further refinement (e.g., to allow for differential DNA repair/apoptosis over different dose regions). The model has been successfully used to explain nonlinear dose-response curves for low-linear-energy-transfer (LET) radiation-induced mutations (in vivo) and neoplastic transformation (in vitro). Relative risk dose-response functions developed for neoplastic transformation have been adapted for application to cancer relative risk evaluation for irradiated humans. Our low-dose research along with that conducted by others collectively demonstrate the following regarding induced protection associated with exposure to low doses of low-LET radiation: (1) protects against cell killing by high-LET alpha particles; (2) protects against spontaneous chromosomal damage; (3) protects against spontaneous mutations and neoplastic transformations; (4) suppresses mutations induced by a large radiation dose even when the low dose is given after the large dose; (5) suppresses spontaneous and alpha-radiation-induced cancers; (6) suppresses metastasis of existing cancer; (7) extends tumor latent period; (8) protects against diseases other than cancer; and (9) extends life expectancy. These forms of radiation-induced protection are called adapted protection as they relate to induced adaptive response. Thus, low doses and dose rates of low-LET radiation generally protect rather than harm us. These findings invalidate the linear not threshold (LNT) hypothesis which is based on the premise that any amount of radiation is harmful irrespective of its type. The hypothesis also implicates a linear dose-response curve for cancer induction that has a positive slope and no

  5. Simulated Microgravity and Low-Dose/Low-Dose-Rate Radiation Induces Oxidative Damage in the Mouse Brain.

    PubMed

    Mao, Xiao Wen; Nishiyama, Nina C; Pecaut, Michael J; Campbell-Beachler, Mary; Gifford, Peter; Haynes, Kristine E; Becronis, Caroline; Gridley, Daila S

    2016-06-01

    Microgravity and radiation are stressors unique to the spaceflight environment that can have an impact on the central nervous system (CNS). These stressors could potentially lead to significant health risks to astronauts, both acutely during the course of a mission or chronically, leading to long-term, post-mission decrements in quality of life. The CNS is sensitive to oxidative injury due to high concentrations of oxidizable, unsaturated lipids and low levels of antioxidant defenses. The purpose of this study was to evaluate oxidative damage in the brain cortex and hippocampus in a ground-based model for spaceflight, which includes prolonged unloading and low-dose radiation. Whole-body low-dose/low-dose-rate (LDR) gamma radiation using (57)Co plates (0.04 Gy at 0.01 cGy/h) was delivered to 6 months old, mature, female C57BL/6 mice (n = 4-6/group) to simulate the radiation component. Anti-orthostatic tail suspension was used to model the unloading, fluid shift and physiological stress aspects of the microgravity component. Mice were hindlimb suspended and/or irradiated for 21 days. Brains were isolated 7 days or 9 months after irradiation and hindlimb unloading (HLU) for characterization of oxidative stress markers and microvessel changes. The level of 4-hydroxynonenal (4-HNE) protein, an oxidative specific marker for lipid peroxidation, was significantly elevated in the cortex and hippocampus after LDR + HLU compared to controls (P < 0.05). The combination group also had the highest level of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression compared to controls (P < 0.05). There was a significant decrease in superoxide dismutase (SOD) expression in the animals that received HLU only or combined LDR + HLU compared to control (P < 0.05). In addition, 9 months after LDR and HLU exposure, microvessel densities were the lowest in the combination group, compared to age-matched controls in the cortex (P < 0.05). Our data provide the first evidence

  6. Analysis of the Mortality Experience amongst U.S. Nuclear Power Industry Workers after Chronic Low-Dose Exposure to Ionizing Radiation

    SciTech Connect

    Howe, Geoffrey R.; Zablotska, Lydia B.; Fix, Jack J.; Egel, John N.; Buchanan, Jeffrey A.

    2004-11-01

    Workers employed in 15 utilities that generate nuclear power in the United States have been followed for up to 18 years between 1979 and 1997. Their cumulative dose from whole-body ionizing radiation has been determined from the dose records maintained by the facilities themselves and the REIRS and REMS systems maintained by the Nuclear Regulatory Commission and the Department of Energy, respectively. Mortality in the cohort from a number of causes has been analyzed with respect to individual radiation doses. The cohort displays a very substantial healthy worker effect, i.e. considerably lower cancer and noncancer mortality than the general population. Based on 26 and 368 deaths, respectively, positive though statistically nonsignificant associations were seen for mortality from leukemia (excluding chronic lymphocytic leukemia) and all solid cancers combined, with excess relative risks per sievert of 5.67 (95% confidence interval (CI) -2.56, 30.4) and 0.596 (95% CI -2.01, 4.64), respectively. These estimates are very similar to those from the atomic bomb survivors study, though the wide confidence intervals are also consistent with lower or higher risk estimates. A strong positive and statistically significant association between radiation dose and deaths from arteriosclerotic heart disease including coronary heart disease was also observed in the cohort, with an ERR of 8.78 (95% CI 2.10, 20.0). While associations with heart disease have been reported in some other occupational studies, the magnitude of the present association is not consistent with them and therefore needs cautious interpretation and merits further attention. At present, the relatively small number of deaths and the young age of the cohort (mean age at end of follow-up is 45 years) limit the power of the study, but further follow-up and the inclusion of the present data in an ongoing IARC combined analysis of nuclear workers from 15 countries will have greater power for testing the main hypotheses

  7. Low-dose radiation: a cause of breast cancer

    SciTech Connect

    Land, C.E.

    1980-08-15

    It is likely that the breast is the organ most sensitive to radiation carcinogenesis in postpubertal women. Studies of different exposed populations have yielded remarkably consistent results, in spite of wide differences in underlying breast cancer rates and conditions of exposure. Excess risk is approximately proportional to dose, and is relatively independent of ionization density and fractionization of dose. This implies that the risk associated with low-dose exposures to ionizing radiation can be estimated with some confidence from higher-dose data. Excess risk is heavily dependent on age at exposure but relatively independent of population differences in normal risk. The temporal patterns after exposure of both radiation-induced and naturally occurring breast cancer are similar, suggesting a strong influence of factors other than radiation on radiation-induced breast cancer. Uncertainties remain about risks from exposures before puberty and after menopause.

  8. Effect of low dose rate radiation on cell growth kinetics.

    PubMed Central

    Gregg, E C; Yau, T M; Kim, S C

    1979-01-01

    Experimental determinations were made of cell number as a function of time for two strains of L5178Y mammalian cells maintained continuously in various environments of radiation. One strain possessed a shoulder in its dose response curve whereas the other did not. Neither strain showed any significant difference in growth rate for interdivision doses on the order of the median lethal dose or less delivered continuously at a low dose rate or pulsed every 4 h at a high instantaneous dose rate. It was also shown that large numbers of dead cells have little effect on growth rate and that these dead cells last as discrete entities for many days. A simple theory of growth rate in the presence of radiation is presented, and the agreement with the observations implies that there is no effect of any sublethal low dose rate radiation received in one generation on the growth rate or radiation sensitivity of the succeeding generation. Further analysis of the data also showed that for the no-shoulder cells at 37 degrees C, tritiated water had a relative biological effect close to unity for cell sterilization. PMID:262446

  9. Influence of Exposure to Chronic Persistent Low-Dose Ionizing Radiation on the Tumor Biology of Clear-Cell Renal-Cell Carcinoma. An Immunohistochemical and Morphometric Study of Angiogenesis and Vascular Related Factors.

    PubMed

    Ruiz-Saurí, Amparo; Valencia-Villa, Gerardo; Romanenko, Alina; Pérez, Jesús; García, Raúl; García, Heydi; Benavent, José; Sancho-Tello, María; Carda, Carmen; Llombart-Bosch, Antonio

    2016-10-01

    Increased angiogenesis is related to boosted growth and malignancy in carcinomas. "Chronic Persistent Low-Dose Ionizing Radiation" (CPLDIR) exposure increases incidence and aggressive behavior of clear-cell renal-cell carcinoma (CCRCC). The aim was to study the biology of angiogenesis, including microvessel density (MVD), in human clear-cell renal-cell carcinomas (CCRCC) originating from a radio-contaminated geographical area (Ukraine) and to compare with similar tumors diagnosed in non-contaminated regions of Europe (Spain, Valencia) and Latin America (Colombia, Barranquilla). MVD was comparatively examined in 124 patients diagnosed with CCRCC from three geographical areas by means of digital micro-imaging and computerized analysis. Additionally, 50 adult normal kidneys were used for controls (autopsy kidneys from Valencia and Barranquilla). Furthermore, an immunohistochemical study of several vascular related growth factors was undertaken using a similar methodology. MVD as well as VEFG are the most discriminating factors associated with an aggressive behavior of CCRCC. Their expression increased in proportion to the level of exposure to chronic low-dose ionizing radiation in Ukrainian patients in the 25 years since the Chernobyl accident substantiated by comparison with the two control groups of renal carcinomas present in non-irradiated areas (Spain and Colombia). No major biological differences relating to angiogenesis appear to exist between the CCRCC diagnosed in two distant geographical areas of the world. HIF-1α expression was similar in all groups, with no statistical significance. Present findings demonstrate the existence of a significant relationship between MVD and VEGF in CCRCC: an increased expression of VEGF is associated with a high level of angiogenesis. PMID:27156071

  10. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    SciTech Connect

    Kleiman, Norman Jay

    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

  11. Non linear processes modulated by low doses of radiation exposure

    NASA Astrophysics Data System (ADS)

    Mariotti, Luca; Ottolenghi, Andrea; Alloni, Daniele; Babini, Gabriele; Morini, Jacopo; Baiocco, Giorgio

    The perturbation induced by radiation impinging on biological targets can stimulate the activation of several different pathways, spanning from the DNA damage processing to intra/extra -cellular signalling. In the mechanistic investigation of radiobiological damage this complex “system” response (e.g. omics, signalling networks, micro-environmental modifications, etc.) has to be taken into account, shifting from a focus on the DNA molecule solely to a systemic/collective view. An additional complication comes from the finding that the individual response of each of the involved processes is often not linear as a function of the dose. In this context, a systems biology approach to investigate the effects of low dose irradiations on intra/extra-cellular signalling will be presented, where low doses of radiation act as a mild perturbation of a robustly interconnected network. Results obtained through a multi-level investigation of both DNA damage repair processes (e.g. gamma-H2AX response) and of the activation kinetics for intra/extra cellular signalling pathways (e.g. NFkB activation) show that the overall cell response is dominated by non-linear processes - such as negative feedbacks - leading to possible non equilibrium steady states and to a poor signal-to-noise ratio. Together with experimental data of radiation perturbed pathways, different modelling approaches will be also discussed.

  12. Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity.

    PubMed

    Kudryasheva, N S; Rozhko, T V

    2015-04-01

    The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1--absence of effects (stress recognition), 2--activation (adaptive response), and 3--inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. PMID:25644753

  13. The spectrum of mutation produced by low dose radiation

    SciTech Connect

    Morley,Alexander,A; Turner, David,R

    2004-10-31

    Inherited mutations are the basis of evolution and acquired mutations in humans are important in ageing, cancer and possibly various forms of tissue degeneration. Mutations are responsible for many of the long-term effects of radiation. However, sensitive direct detection of mutations in humans has been difficult. The aims of the project were to develop methods for the sensitive enumeration of mutations in DNA, to measure mutation frequencies in a wide variety of tissue types and to quantify the mutational effect of direct oxidative damage produced by radiation, at both high and low doses. The project was successful in developing a sensitive method which could detect mutations directly in the genetic material, DNA at a sensitivity of 1 mutated molecule in 1000000000 unmutated molecules. However a number of methodological problems had to be overcome and lack of ongoing funding made it impossible to fulfill all of the aims of the project

  14. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    SciTech Connect

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F.; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A.

    2014-10-22

    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. Finally, 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.

  15. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    DOE PAGESBeta

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; et al

    2014-10-22

    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 initiallymore » 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. Finally, 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.« less

  16. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    PubMed Central

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F.; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A.

    2014-01-01

    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. PMID:25337914

  17. Differentially Expressed Genes Associated with Low-Dose Gamma Radiation

    NASA Astrophysics Data System (ADS)

    Hegyesi, Hargita; Sándor, Nikolett; Schilling, Boglárka; Kis, Enikő; Lumniczky, Katalin; Sáfrány, Géza

    We have studied low dose radiation induced gene expression alterations in a primary human fibroblast cell line using Agilent's whole human genome microarray. Cells were irradiated with 60Co γ-rays (0; 0.1; 0.5 Gy) and 2 hours later total cellular RNA was isolated. We observed differential regulation of approximately 300-500 genes represented on the microarray. Of these, 126 were differentially expressed at both doses, among them significant elevation of GDF-15 and KITLG was confirmed by qRT-PCR. Based on the transcriptional studies we selected GDF-15 to assess its role in radiation response, since GDF-15 is one of the p53 gene targets and is believed to participate in mediating p53 activities. First we confirmed gamma-radiation induced dose-dependent changes in GDF-15 expression by qRT-PCR. Next we determined the effect of GDF-15 silencing on radiosensitivity. Four GDF-15 targeting shRNA expressing lentiviral vectors were transfected into immortalized human fibroblast cells. We obtained efficient GDF-15 silencing in one of the four constructs. RNA interference inhibited GDF-15 gene expression and enhanced the radiosensitivity of the cells. Our studies proved that GDF-15 plays an essential role in radiation response and may serve as a promising target in radiation therapy.

  18. Responses to Low Doses of Ionizing Radiation in Biological Systems

    PubMed Central

    Feinendegen, Ludwig E.; Pollycove, Myron; Sondhaus, Charles A.

    2004-01-01

    Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems. To examine tissue effects specific for low-dose radiation, (1) absorbed dose in tissue is replaced by the sum of the energies deposited by each track event, or hit, in a cell-equivalent tissue micromass (1 ng) in all micromasses exposed, that is, by the mean energy delivered by all microdose hits in the exposed micromasses, with cell dose expressing the total energy per micromass from multiple microdoses; and (2) tissue effects are related to cell damage and protective cellular responses per average microdose hit from a given radiation quality for all such hits in the exposed micromasses. The probability of immediate DNA damage per low-linear-energy-transfer (LET) average micro-dose hit is extremely small, increasing over a certain dose range in proportion to the number of hits. Delayed temporary adaptive protection (AP) involves (a) induced detoxification of reactive oxygen species, (b) enhanced rate of DNA repair, (c) induced removal of damaged cells by apoptosis followed by normal cell replacement and by cell differentiation, and (d) stimulated immune response, all with corresponding changes in gene expression. These AP categories may last from less than a day to weeks and be tested by cell responses against renewed irradiation. They operate physiologically against nonradiogenic, largely endogenous DNA damage, which occurs abundantly and continually. Background radiation damage caused by rare microdose hits per micromass is many orders of magnitude less frequent. Except for apoptosis, AP increasingly fails above about 200 mGy of low-LET radiation, corresponding to about 200 microdose hits per exposed micromass. This ratio appears to exceed

  19. Compelling Issues Compounding the Understanding of Low Dose Radiation Effects: But Do They Matter?

    PubMed

    Morgan, William F

    2016-03-01

    Recent advances in low dose radiation research have raised a number of compelling issues that have compounded the understanding of low dose radiation effects. Here some of them are outlined: the linear no-threshold model for predicting effects at low radiation doses, dose rate effectiveness factor, attributability, and public perception of low dose radiation effects. The impact of changes in any of these hotly debated issues on radiation protection is considered.

  20. Sensitivity to low-dose radiation in radiosensitive wasted mice

    SciTech Connect

    Paunesku, T.; Protic, M.; Woloschak, G. E.

    1999-11-12

    Mice homozygous for the autosomal recessive wasted mutation (wst/wst) have abnormalities in T-lymphocytes and in the anterior motor neuron cells of the spinal cord, leading to sensitivity to low doses of ionizing radiation, hind limb paralysis, and immunodeficiency. This defect results in a failure to gain weight by 20 days and death at 28 days of age. The wasted mutation (previously mapped to mouse chromosome 2) is shown to be a 3-bp deletion in a T-cell-specific (and perhaps motor-neuron-specific) regulatory region (promoter) of the proliferating cell nuclear antigen (PCNA) gene on mouse chromosome 2. A regulatory element is also shown to be important in PCNA expression in T-lymphocytes and motor neuron cells afflicted by the 3-bp deletion in the PCNA promoter. The model is as follows: Absence of PCNA expression in the thymuses (and motor neurons) of wasted mice causes cellular apoptosis; this absence of expression is mediated by a positive transactor that can bind to the wild-type but not the wasted mutant PCNA promoter; the bound protein induces late expression of PCNA in T-lymphocytes and prevents onset of radiation sensitivity in the cells.

  1. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    PubMed

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals. PMID:24772825

  2. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    PubMed

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals.

  3. Risk of cancer subsequent to low-dose radiation.

    PubMed

    Warren, S

    1980-10-01

    Prominent among media items related to the Three Mile Island episode were prophecies of future cancers. The credibility of some of these estimates are discussed. The average person has been exposed by the age of 50 to 2.5 rad (0.025 Gy) from natural background. We define low doses as under 25 rad (0.25 Gy). The most heavily exposed members of the general population during the Three Mile Island event received 83 mrad (0.83 mGy). Those exposed to 2500 mrad (25 mGy) would show no pathologically recognizable effects of radiation though there is evidence that chromosomal damage may occur with doses about 1 rad (0.01 Gy). An official stated among the consequences of the Three Mile Island accident that two additional cancer deaths would result. No epidemiologist could detect such an increase in the population at risk. It has been generally agreed that the linear hypothesis is useful for determining protection standards, not prognosis. Objective criteria for pathologic diagnosis of cause-effect relations are presented. PMID:7430985

  4. [Relationship to Carcinogenesis of Repetitive Low-Dose Radiation Exposure].

    PubMed

    Ootsuyama, Akira

    2016-06-01

    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. PMID:27302731

  5. [Relationship to Carcinogenesis of Repetitive Low-Dose Radiation Exposure].

    PubMed

    Ootsuyama, Akira

    2016-06-01

    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.

  6. Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. Session 5: Future of Radiation Protection Regulations.

    PubMed

    Cool, Donald A

    2016-03-01

    The system of radiological protection is a prospective approach to protection of individuals in all exposure situations. It must be applied equitably across all age groups and all populations. This is a very different circumstance from dose assessment for a particular individual where the unique characteristics of the individual and the exposure can be taken into account. Notwithstanding the ongoing discussions on the possible shape of the dose response at low doses and dose rates, the prospective system of protection has therefore historically used a linear assumption as a pragmatic, prudent and protective approach. These radiation protection criteria are not intended to be a demarcation between "safe" and "unsafe" and are the product of a risk-informed judgement that includes inputs from science, ethics, and experience. There are significant implications for different dose response relationships. A linear model allows for equal treatment of an exposure, irrespective of the previously accumulated exposure. In contrast, other models would predict different implications. Great care is therefore needed in separating the thinking around risk assessment from risk management, and prospective protection for all age groups and genders from retrospective assessment for a particular individual. In the United States, the prospective regulatory structure functions effectively because of assumptions that facilitate independent treatment of different types of exposures, and which provide pragmatic and prudent protection. While the a linear assumption may, in fact, not be consistent with the biological reality, the implications of a different regulatory model must be considered carefully.

  7. Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. Session 5: Future of Radiation Protection Regulations.

    PubMed

    Cool, Donald A

    2016-03-01

    The system of radiological protection is a prospective approach to protection of individuals in all exposure situations. It must be applied equitably across all age groups and all populations. This is a very different circumstance from dose assessment for a particular individual where the unique characteristics of the individual and the exposure can be taken into account. Notwithstanding the ongoing discussions on the possible shape of the dose response at low doses and dose rates, the prospective system of protection has therefore historically used a linear assumption as a pragmatic, prudent and protective approach. These radiation protection criteria are not intended to be a demarcation between "safe" and "unsafe" and are the product of a risk-informed judgement that includes inputs from science, ethics, and experience. There are significant implications for different dose response relationships. A linear model allows for equal treatment of an exposure, irrespective of the previously accumulated exposure. In contrast, other models would predict different implications. Great care is therefore needed in separating the thinking around risk assessment from risk management, and prospective protection for all age groups and genders from retrospective assessment for a particular individual. In the United States, the prospective regulatory structure functions effectively because of assumptions that facilitate independent treatment of different types of exposures, and which provide pragmatic and prudent protection. While the a linear assumption may, in fact, not be consistent with the biological reality, the implications of a different regulatory model must be considered carefully. PMID:26808877

  8. A meta-analysis of leukaemia risk from protracted exposure to low-dose gamma radiation

    PubMed Central

    Schubauer-Berigan, M K

    2010-01-01

    Context More than 400 000 workers annually receive a measurable radiation dose and may be at increased risk of radiation-induced leukaemia. It is unclear whether leukaemia risk is elevated with protracted, low-dose exposure. Objective We conducted a meta-analysis examining the relationship between protracted low-dose ionising radiation exposure and leukaemia. Data sources Reviews by the National Academies and United Nations provided a summary of informative studies published before 2005. PubMed and Embase databases were searched for additional occupational and environmental studies published between 2005 and 2009. Study selection We selected 23 studies that: (1) examined the association between protracted exposures to ionising radiation and leukaemia excluding chronic lymphocytic subtype; (2) were a cohort or nested case–control design without major bias; (3) reported quantitative estimates of exposure; and (4) conducted exposure–response analyses using relative or excess RR per unit exposure. Methods Studies were further screened to reduce information overlap. Random effects models were developed to summarise between-study variance and obtain an aggregate estimate of the excess RR at 100 mGy. Publication bias was assessed by trim and fill and Rosenthal's file drawer methods. Results We found an ERR at 100 mGy of 0.19 (95% CI 0.07 to 0.32) by modelling results from 10 studies and adjusting for publication bias. Between-study variance was not evident (p=0.99). Conclusions Protracted exposure to low-dose gamma radiation is significantly associated with leukaemia. Our estimate agreed well with the leukaemia risk observed among exposed adults in the Life Span Study (LSS) of atomic bomb survivors, providing increased confidence in the current understanding of leukaemia risk from ionising radiation. However, unlike the estimates obtained from the LSS, our model provides a precise, quantitative summary of the direct estimates of excess risk from studies of

  9. Genetic Factors Affecting Susceptibility to Low Dose & Low Dose-Rate Radiation

    SciTech Connect

    Bedford, Joel

    2014-04-18

    Our laboratory has, among other things, developed and used the gamma H2AX focus assay and other chromosomal and cell killing assays to show that differences in this DNA double strand break (dsb) related response can be clearly and distinctly demonstrated for cells which are mildly hyper-radiosensitive such as those associated with A-T heterozygosity. We have found this level of mild hypersensitivity for cells from some 20 to 30 % of apparently normal individuals and from apparently normal parents of Retinoblastoma patients. We found significant differences in gene expression in somatic cells from unaffected parents of Rb patients as compared with normal controls, suggesting that these parents may harbor some as yet unidentified genetic abnormality. In other experiments we sought to determine the extent of differences in normal human cellular reaponses to radiation depending on their irradiation in 2D monolayer vs 3D organized acinar growth conditions. We exmined cell reproductive death, chromosomal aberration induction, and the levels of γ-H2AX foci in cells after single acute gamma-ray doses and immediately after 20 hours of irradiation at a dose rate of 0.0017 Gy/min. We found no significant differences in the dose-responses of these cells under the 2D or 3D growth conditions. While this does not mean such differences cannot occur in other situations, it does mean that they do not generally or necessarily occur. In another series of studies in collaboration with Dr Chuan Li, with supprt from this current grant. We reported a role for apoptotic cell death in promoting wound healing and tissue regeneration in mice. Apoptotic cells released growth signals that stimulated the proliferation of progenitor or stem cells. In yet another collaboration with Dr, B. Chen with funds from this grant, the relative radiosensitivity to cell killing as well as chromosomal instability of 13 DNA-PKcs site-directed mutant cell lines (defective at phosphorylation sites or kinase

  10. [Cytogenetic indices for somatic mutagenesis in mammals exposed to chronic low-dose irradiation].

    PubMed

    Kostenko, S A; Ermakova, O V; Sushko, S N; Fyedorova, E V; Dzhus, P P; Baschlykova, L A; Kurylenko, Yu F; Raskosha, O V; Savin, A O; Shaforost, A S

    2015-01-01

    We used cytogenetic analysis in the studies of the biological effects of a radiation factor of natural and artificial origin (under conditions ofthe 30-km exclusion zone ofthe Chernobyl experimental landfills in Ukraine, Belarus and Russia). The studies have been performed on various types of mammals: domestic animals--cows, pigs, horses and rodents--root voles, the Af mouse line, and yellow necked field mouse, bank voles. We found significant changes in the level of MN and chromosomal aberrations in the animals that were exposed to the conditions of chronic low-dose radiation for a long time (bothin the habitat and upon exposure in the Chernobyl zone) regardless of the type of animal and nature of contamination.

  11. Cellular response to low dose radiation: Role of phosphatidylinositol-3 kinase like kinases

    SciTech Connect

    Balajee, A.S.; Meador, J.A.; Su, Y.

    2011-03-24

    It is increasingly realized that human exposure either to an acute low dose or multiple chronic low doses of low LET radiation has the potential to cause different types of cancer. Therefore, the central theme of research for DOE and NASA is focused on understanding the molecular mechanisms and pathways responsible for the cellular response to low dose radiation which would not only improve the accuracy of estimating health risks but also help in the development of predictive assays for low dose radiation risks associated with tissue degeneration and cancer. The working hypothesis for this proposal is that the cellular mechanisms in terms of DNA damage signaling, repair and cell cycle checkpoint regulation are different for low and high doses of low LET radiation and that the mode of action of phosphatidylinositol-3 kinase like kinases (PIKK: ATM, ATR and DNA-PK) determines the dose dependent cellular responses. The hypothesis will be tested at two levels: (I) Evaluation of the role of ATM, ATR and DNA-PK in cellular response to low and high doses of low LET radiation in simple in vitro human cell systems and (II) Determination of radiation responses in complex cell microenvironments such as human EpiDerm tissue constructs. Cellular responses to low and high doses of low LET radiation will be assessed from the view points of DNA damage signaling, DNA double strand break repair and cell cycle checkpoint regulation by analyzing the activities (i.e. post-translational modifications and kinetics of protein-protein interactions) of the key target proteins for PI-3 kinase like kinases both at the intra-cellular and molecular levels. The proteins chosen for this proposal are placed under three categories: (I) sensors/initiators include ATM ser1981, ATR, 53BP1, gamma-H2AX, MDC1, MRE11, Rad50 and Nbs1; (II) signal transducers include Chk1, Chk2, FANCD2 and SMC1; and (III) effectors include p53, CDC25A and CDC25C. The primary goal of this proposal is to elucidate the

  12. Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris

    DOE PAGESBeta

    Stark, Karolina; Scott, David E.; Tsyusko, Olga; Coughlin, Daniel P.; Hinton, Thomas G.; Amendola, Roberto

    2015-04-30

    Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d⁻¹, resulting in total doses up to 15.8 Gy. Radiation treatments did notmore » affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d⁻¹ and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.« less

  13. Multi-Level Effects of Low Dose Rate Ionizing Radiation on Southern Toad, Anaxyrus [Bufo] terrestris.

    PubMed

    Stark, Karolina; Scott, David E; Tsyusko, Olga; Coughlin, Daniel P; Hinton, Thomas G

    2015-01-01

    Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development -embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of 137Cs at 0.13, 2.4, 21, and 222 mGy d-1, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21 mGy d-1 and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.

  14. Multi-Level Effects of Low Dose Rate Ionizing Radiation on Southern Toad, Anaxyrus [Bufo] terrestris

    PubMed Central

    Stark, Karolina; Scott, David E.; Tsyusko, Olga; Coughlin, Daniel P.; Hinton, Thomas G.

    2015-01-01

    Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of 137Cs at 0.13, 2.4, 21, and 222 mGy d-1, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21 mGy d-1 and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae. PMID:25927361

  15. [The advance of model of action in low-dose chronic benzene exposure induced hematotoxicity].

    PubMed

    Gao, Chen; Zhang, Zhengbao; Chen, Liping; Chen, Wen

    2015-09-01

    Benzene is classified as Group 1 carcinogen by IARC. It has been found that benzene induces hematotoxicity even in low dose exposure. The identification of key events during benzene induced hematotoxicty leads to adjustment of occupational exposure limits of benzene. In this review, we focus on the exposure, metabolism, target organs, key epigenetic changes, toxicty effects and end points of low-dose chronic benzene exposure induced hematotoxicity and finally discuss the perspectives on the future study of this area.

  16. Mitochondrial-Derived Oxidants and Cellular Responses to Low Dose/Low LET Ionizing Radiation

    SciTech Connect

    Spitz, Douglas R.

    2009-11-09

    Exposure to ionizing radiation results in the immediate formation of free radicals and other reactive oxygen species (ROS). It has been assumed that the subsequent injury processes leading to genomic instability and carcinogenesis following radiation, derive from the initial oxidative damage caused by these free radicals and ROS. It is now becoming increasingly obvious that metabolic oxidation/reduction (redox) reactions can be altered by irradiation leading to persistent increases in steady-state levels of intracellular free radicals and ROS that contribute to the long term biological effects of radiation exposure by causing chronic oxidative stress. The objective during the last period of support (DE-FG02-05ER64050; 5/15/05-12/31/09) was to determine the involvement of mitochondrial genetic defects in metabolic oxidative stress and the biological effects of low dose/low LET radiation. Aim 1 was to determine if cells with mutations in succinate dehydrogenase (SDH) subunits C and D (SDHC and SDHD in mitochondrial complex II) demonstrated increases in steady-state levels of reactive oxygen species (ROS; O2•- and H2O2) as well as demonstrating increased sensitivity to low dose/low LET radiation (10 cGy) in cultured mammalian cells. Aim #2 was to determine if mitochondrially-derived ROS contributed to increased sensitivity to low dose/low LET radiation in mammalian cells containing mutations in SDH subunits. Aim #3 was to determine if a causal relationship existed between increases in mitochondrial ROS production, alterations in electron transport chain proteins, and genomic instability in the progeny of irradiated cells. Evidence gathered in the 2005-2009 period of support demonstrated that mutations in genes coding for mitochondrial electron transport chain proteins (ETC); either Succinate Dehydrogenase (SDH) subunit C (SDHC) or subunit D (SDHD); caused increased ROS production, increased genomic instability, and increased sensitivity to low dose/low LET radiation

  17. Gamma radiation at a human relevant low dose rate is genotoxic in mice

    NASA Astrophysics Data System (ADS)

    Graupner, Anne; Eide, Dag M.; Instanes, Christine; Andersen, Jill M.; Brede, Dag A.; Dertinger, Stephen D.; Lind, Ole C.; Brandt-Kjelsen, Anicke; Bjerke, Hans; Salbu, Brit; Oughton, Deborah; Brunborg, Gunnar; Olsen, Ann K.

    2016-09-01

    Even today, 70 years after Hiroshima and accidents like in Chernobyl and Fukushima, we still have limited knowledge about the health effects of low dose rate (LDR) radiation. Despite their human relevance after occupational and accidental exposure, only few animal studies on the genotoxic effects of chronic LDR radiation have been performed. Selenium (Se) is involved in oxidative stress defence, protecting DNA and other biomolecules from reactive oxygen species (ROS). It is hypothesised that Se deficiency, as it occurs in several parts of the world, may aggravate harmful effects of ROS-inducing stressors such as ionising radiation. We performed a study in the newly established LDR-facility Figaro on the combined effects of Se deprivation and LDR γ exposure in DNA repair knockout mice (Ogg1‑/‑) and control animals (Ogg1+/‑). Genotoxic effects were seen after continuous radiation (1.4 mGy/h) for 45 days. Chromosomal damage (micronucleus), phenotypic mutations (Pig-a gene mutation of RBCCD24‑) and DNA lesions (single strand breaks/alkali labile sites) were significantly increased in blood cells of irradiated animals, covering three types of genotoxic activity. This study demonstrates that chronic LDR γ radiation is genotoxic in an exposure scenario realistic for humans, supporting the hypothesis that even LDR γ radiation may induce cancer.

  18. Gamma radiation at a human relevant low dose rate is genotoxic in mice

    PubMed Central

    Graupner, Anne; Eide, Dag M.; Instanes, Christine; Andersen, Jill M.; Brede, Dag A.; Dertinger, Stephen D.; Lind, Ole C.; Brandt-Kjelsen, Anicke; Bjerke, Hans; Salbu, Brit; Oughton, Deborah; Brunborg, Gunnar; Olsen, Ann K.

    2016-01-01

    Even today, 70 years after Hiroshima and accidents like in Chernobyl and Fukushima, we still have limited knowledge about the health effects of low dose rate (LDR) radiation. Despite their human relevance after occupational and accidental exposure, only few animal studies on the genotoxic effects of chronic LDR radiation have been performed. Selenium (Se) is involved in oxidative stress defence, protecting DNA and other biomolecules from reactive oxygen species (ROS). It is hypothesised that Se deficiency, as it occurs in several parts of the world, may aggravate harmful effects of ROS-inducing stressors such as ionising radiation. We performed a study in the newly established LDR-facility Figaro on the combined effects of Se deprivation and LDR γ exposure in DNA repair knockout mice (Ogg1−/−) and control animals (Ogg1+/−). Genotoxic effects were seen after continuous radiation (1.4 mGy/h) for 45 days. Chromosomal damage (micronucleus), phenotypic mutations (Pig-a gene mutation of RBCCD24−) and DNA lesions (single strand breaks/alkali labile sites) were significantly increased in blood cells of irradiated animals, covering three types of genotoxic activity. This study demonstrates that chronic LDR γ radiation is genotoxic in an exposure scenario realistic for humans, supporting the hypothesis that even LDR γ radiation may induce cancer. PMID:27596356

  19. Gamma radiation at a human relevant low dose rate is genotoxic in mice.

    PubMed

    Graupner, Anne; Eide, Dag M; Instanes, Christine; Andersen, Jill M; Brede, Dag A; Dertinger, Stephen D; Lind, Ole C; Brandt-Kjelsen, Anicke; Bjerke, Hans; Salbu, Brit; Oughton, Deborah; Brunborg, Gunnar; Olsen, Ann K

    2016-01-01

    Even today, 70 years after Hiroshima and accidents like in Chernobyl and Fukushima, we still have limited knowledge about the health effects of low dose rate (LDR) radiation. Despite their human relevance after occupational and accidental exposure, only few animal studies on the genotoxic effects of chronic LDR radiation have been performed. Selenium (Se) is involved in oxidative stress defence, protecting DNA and other biomolecules from reactive oxygen species (ROS). It is hypothesised that Se deficiency, as it occurs in several parts of the world, may aggravate harmful effects of ROS-inducing stressors such as ionising radiation. We performed a study in the newly established LDR-facility Figaro on the combined effects of Se deprivation and LDR γ exposure in DNA repair knockout mice (Ogg1(-/-)) and control animals (Ogg1(+/-)). Genotoxic effects were seen after continuous radiation (1.4 mGy/h) for 45 days. Chromosomal damage (micronucleus), phenotypic mutations (Pig-a gene mutation of RBC(CD24-)) and DNA lesions (single strand breaks/alkali labile sites) were significantly increased in blood cells of irradiated animals, covering three types of genotoxic activity. This study demonstrates that chronic LDR γ radiation is genotoxic in an exposure scenario realistic for humans, supporting the hypothesis that even LDR γ radiation may induce cancer. PMID:27596356

  20. Low Doses of Radiation are Protective In Vitro and In Vivo: Evolutionary Origins

    PubMed Central

    Mitchel, R.E.J.

    2006-01-01

    Research reports using cells from bacteria, yeast, alga, nematodes, fish, plants, insects, amphibians, birds and mammals, including wild deer, rodents or humans show non-linear radio-adaptive processes in response to low doses of low LET radiation. Low doses increased cellular DNA double-strand break repair capacity, reduced the risk of cell death, reduced radiation or chemically-induced chromosomal aberrations and mutations, and reduced spontaneous or radiation-induced malignant transformation in vitro. In animals, a single low, whole body dose of low LET radiation, increased cancer latency and restored a portion of the life that would have been lost due to either spontaneous or radiation-induced cancer in the absence of the low dose. In genetically normal fetal mice, a prior low dose protected against radiation-induced birth defects. In genetically normal adultmale mice, a low dose prior to a high dose protected the offspring of the mice from heritable mutations produced by the large dose. The results show that low doses of low-LET radiation induce protective effects and that these induced responses have been tightly conserved throughout evolution, suggesting that they are basic responses critical to life. The results also argue strongly that the assumption of a linear increase in risk with increasing dose in humans is unlikely to be correct, and that low doses actually reduce risk. PMID:18648638

  1. Final Technical Report for the grant entitled "Genetic Factors Affecting Susceptibility to Low-Dose Radiation"

    SciTech Connect

    Morgan, William, F., Ph.D., D.Sc.

    2006-11-22

    The goal of this proposal was to test the hypothesis that mice heterozygous for the Nijmegen Breakage Syndrome (NBS1) gene are genetically susceptible to low doses of ionizing radiation. The rationale for this is that patients with NBS are radiation sensitive, because of defects in cellular responses to radiation induced genetic damage and haploinsufficiency at this genetic locus provides the potential for genetic susceptibility to low doses of ionizing radiation. Wild type and heterozygous NBS1 mice were irradiated and followed over their lifetime for radiation induced genomic instability, carcinogenesis and non-specific life shortening. No differences in cytogenetic damage, cancer induction or life span were observed between the hypomorphic mice indicating that genetic imbalance at the NBS1 loci does not modulate low dose radiation sensitivity.

  2. CANCER RISKS ATTRIBUTABLE TO LOW DOSES OF IONIZING RADIATION - ASSESSING WHAT WE REALLY KNOW?

    EPA Science Inventory

    Cancer Risks Attributable to Low Doses of Ionizing Radiation - What Do We Really Know?

    Abstract
    High doses of ionizing radiation clearly produce deleterious consequences in humans including, but not exclusively, cancer induction. At very low radiation doses the situatio...

  3. Thyroid neoplasia following low-dose radiation in childhood

    SciTech Connect

    Ron, E.; Modan, B.; Preston, D.; Alfandary, E.; Stovall, M.; Boice, J.D. Jr. )

    1989-12-01

    The thyroid gland is highly sensitive to the carcinogenic effects of ionizing radiation. Previously, we reported a significant increase of thyroid cancer and adenomas among 10,834 persons in Israel who received radiotherapy to the scalp for ringworm. These findings have now been extended with further follow-up and revised dosimetry. Overall, 98 thyroid tumors were identified among the exposed and 57 among 10,834 nonexposed matched population and 5392 sibling comparison subjects. An estimated thyroid dose of 9 cGy was linked to a fourfold (95% Cl = 2.3-7.9) increase of malignant tumors and a twofold (95% Cl = 1.3-3.0) increase of benign tumors. The dose-response relationship was consistent with linearity. Age was an important modifier of risk with those exposed under 5 years being significantly more prone to develop thyroid tumors than older children. The pattern of radiation risk over time could be described on the basis of a constant multiplication of the background rate, and an absolute risk model was not compatible with the observed data. Overall, the excess relative risk per cGy for thyroid cancer development after childhood exposure is estimated as 0.3, and the absolute excess risk as 13 per 10(6) PY-cGy. For benign tumors the estimated excess relative risk was 0.1 per cGy and the absolute risk was 15 per 10(6) PY-cGy.

  4. Costs, benefits and redundant mechanisms of adaption to chronic low-dose stress in yeast

    PubMed Central

    Markiewicz-Potoczny, Marta; Lydall, David

    2016-01-01

    ABSTRACT All organisms live in changeable, stressful environments. It has been reported that exposure to low-dose stresses or poisons can improve fitness. However, examining the effects of chronic low-dose chemical exposure is challenging. To address this issue we used temperature sensitive mutations affecting the yeast cell division cycle to induce low-dose stress for 40 generation times, or more. We examined cdc13-1 mutants, defective in telomere function, and cdc15-2 mutants, defective in mitotic kinase activity. We found that each stress induced similar adaptive responses. Stress-exposed cells became resistant to higher levels of stress but less fit, in comparison with unstressed cells, in conditions of low stress. The costs and benefits of adaptation to chronic stress were reversible. In the cdc13-1 context we tested the effects of Rad9, a central player in the response to telomere defects, Exo1, a nuclease that degrades defective telomeres, and Msn2 and Msn4, 2 transcription factors that contribute to the environmental stress response. We also observed, as expected, that Rad9 and Exo1 modulated the response of cells to stress. In addition we observed that adaptation to stress could still occur in these contexts, with associated costs and benefits. We conclude that functionally redundant cellular networks control the adaptive responses to low dose chronic stress. Our data suggests that if organisms adapt to low dose stress it is helpful if stress continues or increases but harmful should stress levels reduce. PMID:27628486

  5. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

    EPA Science Inventory

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

  6. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

    EPA Science Inventory

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

  7. Issues in low dose radiation biology: the controversy continues. A perspective.

    PubMed

    Morgan, William F; Bair, William J

    2013-05-01

    Both natural and man-made sources of ionizing radiation contribute to human exposure and consequently pose a possible risk to human health. Much of this is unavoidable, e.g., natural background radiation, but as the use of radiation increases, so does the potential health risk and the public's concerns. This perspective reflects the authors' view of current issues in low dose radiation biology research, highlights some of the controversies therein, and suggests areas of future research to address both issues in low dose radiation research and the controversies. This is a critical time for the radiation sciences and the implications of future research will have a significant impact on radiation protection, medicine, national security, research and industry. The views expressed here are the authors' own and do not represent any institution, organization or funding body.

  8. Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples.

    PubMed

    Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Eric; Banzet, Nathalie; Defoort, Catherine; Bott, Romain; Dublineau, Isabelle; Aigueperse, Jocelyne; Gourmelon, Patrick; Martin, Jean-Charles; Souidi, Maâmar

    2013-01-01

    Because uranium is a natural element present in the earth's crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions. The aim of this study was to assess the biological changes in rats caused by ingestion of natural uranium in drinking water with a mean daily intake of 2.7 mg/kg for 9 months and to identify potential biomarkers related to such a contamination. Subsequently, we observed no pathology and standard clinical tests were unable to distinguish between treated and untreated animals. Conversely, LC-MS metabolomics identified urine as an appropriate biofluid for discriminating the experimental groups. Of the 1,376 features detected in urine, the most discriminant were metabolites involved in tryptophan, nicotinate, and nicotinamide metabolic pathways. In particular, N-methylnicotinamide, which was found at a level seven times higher in untreated than in contaminated rats, had the greatest discriminating power. These novel results establish a proof of principle for using metabolomics to address chronic low-dose uranium contamination. They open interesting perspectives for understanding the underlying biological mechanisms and designing a diagnostic test of exposure.

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

    SciTech Connect

    Hengel, Shawna; Aldrich, Joshua T.; Waters, Katrina M.; Pasa-Tolic, Ljiljana; Stenoien, David L.

    2014-07-29

    To assess molecular responses to low doses of radiation that may be encountered during medical diagnostic procedures, nuclear accidents, or terrorist acts, a quantitative global proteomic approach was used to identify protein alterations in a reconstituted human skin tissue treated with 10 cGy of ionizing radiation. Subcellular fractionation was employed to remove highly abundant structural proteins and provide insight on radiation induced alterations in protein abundance and localization. In addition, peptides were post-fractionated using high resolution 2-dimensional liquid chromatography to increase the dynamic range of detection of protein abundance and translocation changes. Quantitative data was obtained by labeling peptides with 8-plex isobaric iTRAQ tags. A total of 207 proteins were detected with statistically significant alterations in abundance and/or subcellular localization compared to sham irradiated tissues. Bioinformatics analysis of the data indicated that the top canonical pathways affected by low dose radiation are related to cellular metabolism. Among the proteins showing alterations in abundance, localization and proteolytic processing was the skin barrier protein filaggrin which is consistent with our previous observation that ionizing radiation alters profilaggrin processing with potential effects on skin barrier functions. In addition, a large number of proteases and protease regulators were affected by low dose radiation exposure indicating that altered proteolytic activity may be a hallmark of low dose radiation exposure. While several studies have demonstrated altered transcriptional regulation occurs following low dose radiation exposures, the data presented here indicates post-transcriptional regulation of protein abundance, localization, and proteolytic processing play an important role in regulating radiation responses in complex human tissues.

  10. Low Dose Radiation Hypersensitivity is Caused by p53-dependent Apoptosis

    SciTech Connect

    Enns, L; Bogen, K; Wizniak, J; Murtha, A; Weinfeld, M

    2004-04-08

    Exposure to environmental radiation and the application of new clinical modalities, such as radioimmunotherapy, have heightened the need to understand cellular responses to low dose and low-dose rate ionizing radiation. Many tumor cell lines have been observed to exhibit a hypersensitivity to radiation doses below 50 cGy, which manifests as a significant deviation from the clonogenic survival response predicted by a linear-quadratic fit to higher doses. However, the underlying processes for this phenomenon remain unclear. Using a gel microdrop/flow cytometry assay to monitor single cell proliferation at early times post irradiation, we examined the response of human A549 lung carcinoma, T98G glioma and MCF7 breast carcinoma cell lines exposed to gamma radiation doses from 0 to 200 cGy delivered at 0.18 and 22 cGy/min. The A549 and T98G cells, but not MCF7 cells, showed the marked hypersensitivity at doses <50 cGy. To further characterize the low-dose hypersensitivity, we examined the influence of low-dose radiation on cell cycle status and apoptosis by assays for active caspase-3 and phosphatidylserine translocation (annexin-V binding). We observed that caspase-3 activation and annexin-V binding mirrored the proliferation curves for the cell lines. Furthermore, the low-dose hypersensitivity and annexin-V binding to irradiated A549 and T98G cells were eliminated by treating the cells with pifithrin, an inhibitor of p53. When p53-inactive cell lines (2800T skin fibroblasts and HCT116 colorectal carcinoma cells) were examined for similar patterns, we found that there was no HRS and apoptosis was not detectable by annexin-V or caspase-3 assays. Our data therefore suggest that low-dose hypersensitivity is associated with p53-dependent apoptosis.

  11. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

    PubMed

    Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

    2014-05-01

    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 (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) 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. PMID:24366315

  12. Effects of acute low doses of gamma-radiation on erythrocytes membrane.

    PubMed

    Mahmoud, Sherif S; El-Sakhawy, Eman; Abdel-Fatah, Eman S; Kelany, Adel M; Rizk, Rizk M

    2011-03-01

    It is believed that any dose of ionizing radiation may damage cells and that the mutated cells could develop into cancer cells. Additionally, results of research performed over the past century on the effects of low doses of ionizing radiation on biological organisms show beneficial health effects, called hormesis. Much less is known about the cellular response to low doses of ionizing radiation, such as those typical for medical diagnostic procedures, normal occupational exposures or cosmic-ray exposures at flight altitudes. Extrapolating from the effects observed at higher doses to predict changes in cells after low-dose exposure is problematic. We examined the biological effects of low doses (0.01-0.3 Gy) of γ-radiation on the membrane characteristics of erythrocytes of albino rats and carried out osmotic fragility tests and Fourier transform infrared spectroscopy (FTIR). Our results indicate that the lowest three doses in the investigated radiation range, i.e., 0.01, 0.025 and 0.05 Gy, resulted in positive effects on the erythrocyte membranes, while a dose of 0.1 Gy appeared to represent the limiting threshold dose of those positive effects. Doses higher than 0.1 Gy were associated with the denaturation of erythrocyte proteins. PMID:20865271

  13. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

    PubMed

    Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

    2014-05-01

    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 (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) 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.

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

    SciTech Connect

    Tilton, Susan C.; Matzke, Melissa M.; Sowa, Marianne B.; Stenoien, David L.; Weber, Thomas J.; Morgan, William F.; Waters, Katrina M.

    2015-05-15

    The goal of this study was to define pathways regulated by low dose radiation to understand how biological systems respond to subtle perturbations in their environment and prioritize pathways for human health assessment. Using an in vitro 3-D human full thickness skin model, we have examined the temporal response of dermal and epidermal layers to 10 cGy X-ray using transcriptomic, proteomic, phosphoproteomic and metabolomic platforms. Bioinformatics analysis of each dataset independently revealed potential signaling mechanisms affected by low dose radiation, and integrating data shed additional insight into the mechanisms regulating low dose responses in human tissue. We examined direct interactions among datasets (top down approach) and defined several hubs as significant regulators, including transcription factors (YY1, MYC and CREB1), kinases (CDK2, PLK1) and a protease (MMP2). These data indicate a shift in response across time — with an increase in DNA repair, tissue remodeling and repression of cell proliferation acutely (24–72 h). Pathway-based integration (bottom up approach) identified common molecular and pathway responses to low dose radiation, including oxidative stress, nitric oxide signaling and transcriptional regulation through the SP1 factor that would not have been identified by the individual data sets. Significant regulation of key downstream metabolites of nitrative stress was measured within these pathways. Among the features identified in our study, the regulation of MMP2 and SP1 was experimentally validated. Our results demonstrate the advantage of data integration to broadly define the pathways and networks that represent the mechanisms by which complex biological systems respond to perturbation. - Highlights: • Low dose ionizing radiation altered homeostasis in 3D skin tissue model. • Global gene/protein/metabolite data integrated using complementary statistical approaches • Time and location-specific change in matrix regulation

  15. Implications for human and environmental health of low doses of ionising radiation.

    PubMed

    Mothersill, Carmel; Seymour, Colin

    2014-07-01

    The last 20 years have seen a major paradigm shift in radiation biology. Several discoveries challenge the DNA centric view which holds that DNA damage is the critical effect of radiation irrespective of dose. This theory leads to the assumption that dose and effect are simply linked - the more energy deposition, the more DNA damage and the greater the biological effect. This is embodied in radiation protection (RP) regulations as the linear-non-threshold (LNT) model. However the science underlying the LNT model is being challenged particularly in relation to the environment because it is now clear that at low doses of concern in RP, cells, tissues and organisms respond to radiation by inducing responses which are not readily predictable by dose. These include adaptive responses, bystander effects, genomic instability and low dose hypersensitivity, and are commonly described as stress responses, while recognizing that "stress" can be good as well as bad. The phenomena contribute to observed radiation responses and appear to be influenced by genetic, epigenetic and environmental factors, meaning that dose and response are not simply related. The question is whether our discovery of these phenomena means that we need to re-evaluate RP approaches. The so-called "non-targeted" mechanisms mean that low dose radiobiology is very complex and supra linear or sub-linear (even hormetic) responses are possible but their occurrence is unpredictable for any given system level. Issues which may need consideration are synergistic or antagonistic effects of other pollutants. RP, at present, only looks at radiation dose but the new (NTE) radiobiology means that chemical or physical agents, which interfere with tissue responses to low doses of radiation, could critically modulate the predicted risk. Similarly, the "health" of the organism could determine the effect of a given low dose by enabling or disabling a critical response. These issues will be discussed.

  16. Implications for human and environmental health of low doses of ionising radiation.

    PubMed

    Mothersill, Carmel; Seymour, Colin

    2014-07-01

    The last 20 years have seen a major paradigm shift in radiation biology. Several discoveries challenge the DNA centric view which holds that DNA damage is the critical effect of radiation irrespective of dose. This theory leads to the assumption that dose and effect are simply linked - the more energy deposition, the more DNA damage and the greater the biological effect. This is embodied in radiation protection (RP) regulations as the linear-non-threshold (LNT) model. However the science underlying the LNT model is being challenged particularly in relation to the environment because it is now clear that at low doses of concern in RP, cells, tissues and organisms respond to radiation by inducing responses which are not readily predictable by dose. These include adaptive responses, bystander effects, genomic instability and low dose hypersensitivity, and are commonly described as stress responses, while recognizing that "stress" can be good as well as bad. The phenomena contribute to observed radiation responses and appear to be influenced by genetic, epigenetic and environmental factors, meaning that dose and response are not simply related. The question is whether our discovery of these phenomena means that we need to re-evaluate RP approaches. The so-called "non-targeted" mechanisms mean that low dose radiobiology is very complex and supra linear or sub-linear (even hormetic) responses are possible but their occurrence is unpredictable for any given system level. Issues which may need consideration are synergistic or antagonistic effects of other pollutants. RP, at present, only looks at radiation dose but the new (NTE) radiobiology means that chemical or physical agents, which interfere with tissue responses to low doses of radiation, could critically modulate the predicted risk. Similarly, the "health" of the organism could determine the effect of a given low dose by enabling or disabling a critical response. These issues will be discussed. PMID:23664231

  17. Radiation Hormesis: Historical Perspective and Implications for Low-Dose Cancer Risk Assessment

    PubMed Central

    Vaiserman, Alexander M.

    2010-01-01

    Current guidelines for limiting exposure of humans to ionizing radiation are based on the linear-no-threshold (LNT) hypothesis for radiation carcinogenesis under which cancer risk increases linearly as the radiation dose increases. With the LNT model even a very small dose could cause cancer and the model is used in establishing guidelines for limiting radiation exposure of humans. A slope change at low doses and dose rates is implemented using an empirical dose and dose rate effectiveness factor (DDREF). This imposes usually unacknowledged nonlinearity but not a threshold in the dose-response curve for cancer induction. In contrast, with the hormetic model, low doses of radiation reduce the cancer incidence while it is elevated after high doses. Based on a review of epidemiological and other data for exposure to low radiation doses and dose rates, it was found that the LNT model fails badly. Cancer risk after ordinarily encountered radiation exposure (medical X-rays, natural background radiation, etc.) is much lower than projections based on the LNT model and is often less than the risk for spontaneous cancer (a hormetic response). Understanding the mechanistic basis for hormetic responses will provide new insights about both risks and benefits from low-dose radiation exposure. PMID:20585444

  18. Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

    NASA Technical Reports Server (NTRS)

    Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

    2002-01-01

    Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

  19. Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

    SciTech Connect

    Fasola, Carolina E.; Jones, Jennifer C.; Huang, Derek D.; Le, Quynh-Thu; Hoppe, Richard T.; Donaldson, Sarah S.

    2013-08-01

    Purpose: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). Results: At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. Conclusions: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.

  20. Mammalian Tissue Response to Low Dose Ionizing Radiation: The Role of Oxidative Metabolism and Intercellular Communication

    SciTech Connect

    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.

  1. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

    PubMed Central

    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 (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to 239Pu. 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. PMID:24366315

  2. The biobehavioral and neuroimmune impact of low-dose ionizing radiation

    PubMed Central

    York, Jason M; Blevins, Neil A; Meling, Daryl D; Peterlin, Molly B; Gridley, Daila S; Cengel, Keith A; Freund, Gregory G

    2011-01-01

    In the clinical setting, repeated exposures (10–30) to low-doses of ionizing radiation (≤ 200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 h and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice. PMID:21958477

  3. The biobehavioral and neuroimmune impact of low-dose ionizing radiation.

    PubMed

    York, Jason M; Blevins, Neil A; Meling, Daryl D; Peterlin, Molly B; Gridley, Daila S; Cengel, Keith A; Freund, Gregory G

    2012-02-01

    In the clinical setting, repeated exposures (10-30) to low-doses of ionizing radiation (≤200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice.

  4. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium at the EMS 2009 Annual Meeting - September 2006

    SciTech Connect

    Morgan, William F.; von Borstel, Robert C.; Brenner, David; Redpath, J. Leslie; Erickson, Barbra E.; Brooks, Antone L.

    2009-11-12

    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.

  5. Low-dose ethanol consumption allows strength recovery in chronic alcoholic myopathy.

    PubMed

    Fernández-Solà, J; Nicolás, J M; Sacanella, E; Robert, J; Cofan, M; Estruch, R; Urbano-Márquez, A

    2000-01-01

    Chronic skeletal myopathy may affect one third of chronic alcohol misusers. It is generally accepted that abstinence allows partial recovery, and that continued high-dose ethanol consumption progressively deteriorates muscle function. However, the effect of low-dose ethanol consumption in alcoholic myopathy has not been studied. We studied 58 chronic alcoholic male patients with biopsy-proven chronic alcoholic myopathy over 5 years. We evaluated ethanol intake, biochemical and nutritional parameters, and assessed muscle strength. Eighteen patients who remained abstinent showed marked improvement in muscle strength. As expected, the 19 patients who persisted in high-dose ethanol consumption further diminished in their muscle strength. In the 11 patients who maintained low-dose (

  6. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    SciTech Connect

    Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.; Altman, K.I.

    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.

  7. What can be learned from epidemiologic studies of persons exposed to low doses of radiation?

    SciTech Connect

    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.

  8. Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

    PubMed

    Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J; Saran, Anna

    2015-10-13

    There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response. PMID:26359350

  9. Acceleration of atherogenesis in ApoE−/− mice exposed to acute or low-dose-rate ionizing radiation

    PubMed Central

    Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J.; Saran, Anna

    2015-01-01

    There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE−/− mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE−/− females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response. PMID:26359350

  10. Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process

    PubMed Central

    Alessio, Nicola; Del Gaudio, Stefania; Capasso, Stefania; Di Bernardo, Giovanni; Cappabianca, Salvatore; Cipollaro, Marilena; Peluso, Gianfranco; Galderisi, Umberto

    2015-01-01

    Low doses of radiation may have profound effects on cellular function. Individuals may be exposed to low doses of radiation either intentionally for medical purposes or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites. We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSC), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to body's homeostasis. The main outcome of low radiation exposure, besides reduction of cell cycling, is the triggering of senescence, while the contribution to apoptosis is minimal. We also showed that low radiation affected the autophagic flux. We hypothesize that the autophagy prevented radiation deteriorative processes, and its decline contributed to senescence. An increase in ATM staining one and six hours post-irradiation and return to basal level at 48 hours, along with persistent gamma-H2AX staining, indicated that MSC properly activated the DNA repair signaling, though some damages remained unrepaired, mainly in non-cycling cells. This suggested that the impaired DNA repair capacity of irradiated MSC seemed mainly related to the reduced activity of a non-homologous end-joining (NHEJ) system rather than HR (homologous recombination). PMID:25544750

  11. Final Report - Epigenetics of low dose radiation effects in an animal model

    SciTech Connect

    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

  12. Low-dose ionising radiation and cardiovascular diseases--Strategies for molecular epidemiological studies in Europe.

    PubMed

    Kreuzer, Michaela; Auvinen, Anssi; Cardis, Elisabeth; Hall, Janet; Jourdain, Jean-Rene; Laurier, Dominique; Little, Mark P; Peters, Annette; Raj, Ken; Russell, Nicola S; Tapio, Soile; Zhang, Wei; Gomolka, Maria

    2015-01-01

    It is well established that high-dose ionising radiation causes cardiovascular diseases. In contrast, the evidence for a causal relationship between long-term risk of cardiovascular diseases after moderate doses (0.5-5 Gy) is suggestive and weak after low doses (<0.5 Gy). However, evidence is emerging that doses under 0.5 Gy may also increase long-term risk of cardiovascular disease. This would have major implications for radiation protection with respect to medical use of radiation for diagnostic purposes and occupational or environmental radiation exposure. Therefore, it is of great importance to gain information about the presence and possible magnitude of radiation-related cardiovascular disease risk at doses of less than 0.5 Gy. The biological mechanisms implicated in any such effects are unclear and results from epidemiological studies are inconsistent. Molecular epidemiological studies can improve the understanding of the pathogenesis and the risk estimation of radiation-induced circulatory disease at low doses. Within the European DoReMi (Low Dose Research towards Multidisciplinary Integration) project, strategies to conduct molecular epidemiological studies in this field have been developed and evaluated. Key potentially useful European cohorts are the Mayak workers, other nuclear workers, uranium miners, Chernobyl liquidators, the Techa river residents and several diagnostic or low-dose radiotherapy patient cohorts. Criteria for informative studies are given and biomarkers to be investigated suggested. A close collaboration between epidemiology, biology and dosimetry is recommended, not only among experts in the radiation field, but also those in cardiovascular diseases. PMID:26041268

  13. Issues in Low Dose Radiation Biology: The Controversy Continues. A Perspective

    SciTech Connect

    Morgan, William F.; Bair, William J.

    2013-05-01

    Both natural and man-made sources of ionizing radiation contribute to human exposure and consequently pose a risk to human health. Much of this is unavoidable, e.g., natural background radiation, and as the use of radiation in modern medicine and industry increases so does the potential health risk. This perspective reflects the author’s view of current issues in low dose radiation biology research, highlights some of the controversies therein, and suggests areas of future research to address these issues. The views expressed here are the authors own and do not represent any institution, organization or funding body.

  14. Adaption By Low Dose Radiation Exposure: A Look at Scope and Limitations for Radioprotection.

    PubMed

    Mitchel, Ron E J

    2015-01-01

    The procedures and dose limitations used for radiation protection in the nuclear industry are founded on the assumption that risk is directly proportional to dose, without a threshold. Based on this idea that any dose, no matter how small, will increase risk, radiation protection regulations generally attempt to reduce any exposure to "as low as reasonably achievable" (ALARA). We know however, that these regulatory assumptions are inconsistent with the known biological effects of low doses. Low doses induce protective effects, and these adaptive responses are part of a general response to low stress. Adaptive responses have been tightly conserved during evolution, from single celled organisms up to humans, indicating their importance. Here we examine cellular and animal studies that show the influence of radiation induced protective effects on diverse diseases, and examine the radiation dose range that is effective for different tissues in the same animal. The concept of a dose window, with upper and lower effective doses, as well as the effect of multiple stressors and the influence of genetics will also be examined. The effect of the biological variables on low dose responses will be considered from the point of view of the limitations they may impose on any revised radiation protection regulations.

  15. Radiation-Induced Bystander Effects: Evidence for an Adaptive Response to Low Dose Exposures?

    PubMed Central

    Mothersill, Carmel; Seymour, Colin

    2006-01-01

    This paper reviews our current knowledge of the mechanisms underlying the induction of bystander effects by low dose, low-LET ionizing radiation and discusses how they may be related to observed adaptive responses or other protective effects of low dose exposures. Bystander effects appear to be the result of a generalized stress response in tissues or cells. The signals may be produced by all exposed cells, but the response appears to require a quorum in order to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but is p53 independent. While a death response might appear to be adverse, the position is argued in this paper that it is in fact protective and removes damaged cells from the population. Since many cell populations carry damaged cells without being exposed to radiation, so called “background damage”, it is possible that low doses exposures cause removal of cells damaged by agents other than the test dose of radiation. This mechanism would lead to the production of “U-shaped” dose response curves. In this scenario, the level of “adaptive” or beneficial response will be related to the background damage carried by the cell population. This model may be important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors. PMID:18648593

  16. Palliation by Low-Dose Local Radiation Therapy for Indolent Non-Hodgkin Lymphoma

    SciTech Connect

    Chan, Elisa K.; Fung, Sharon; Gospodarowicz, Mary; Hodgson, David; Wells, Woodrow; Sun, Alexander; Pintile, Melania; Tsang, Richard W.

    2011-12-01

    Purpose: The purpose of this study was to assess the efficacy of a 2 Multiplication-Sign 2 Gy (total dose, 4 Gy) palliative radiation therapy (RT) regimen for treating patients with indolent non-Hodgkin lymphoma (NHL) in terms of response rate, response duration, and symptom relief. Methods and Materials: A retrospective chart review was conducted. Between 2003 and 2007, 54 patients with NHL were treated to 85 anatomical sites with a 2 Multiplication-Sign 2 Gy palliative regimen. Local response was assessed by clinical and/or radiographic data. Symptoms before and after treatment for each site treated were obtained from clinical notes in patient medical records. Median follow-up time was 1.3 years. Results: For the 54 patients, the median age at time of treatment was 71.1 years old, and 57% of them were male. Of the 85 disease sites treated, 56% of sites had indolent histology, 28% of sites were diagnosed with chronic lymphocytic leukemia (CLL), 13% of sites had aggressive histology, and 2% of sites were shown to have other histology. Overall response rate (ORR) was 81% (49% complete response [CR], 32% partial response [PR]). The 2-year rate for freedom from local progression was 50% (95% CI, 37%-61%). The ORR for follicular lymphoma, Mucosa associated lymphoid tissue (MALT), and marginal zone lymphoma (MZL) histology was 88%, compared with a 59% rate for CLL histology (p = 0.005). While the ORR was similar for tumors of different sizes, the CR rate for patients with tumors <5 cm tended to be higher than those with tumors >10 cm (CR rate of 57% vs. 27%, respectively; p = 0.06). For the 48 sites with clearly documented symptoms at pretreatment, 92% of sites improved after low-dose RT. Conclusions: Short-course low-dose palliative radiotherapy (2 Multiplication-Sign 2 Gy) is an effective treatment that results in high response rates for indolent non-Hodgkin lymphoma. This treatment regimen provides effective symptomatic relief for tumor bulk of all sizes.

  17. Inconsistencies and open questions regarding low-dose health effects of ionizing radiation.

    PubMed Central

    Nussbaum, R H; Köhnlein, W

    1994-01-01

    The effects on human health of exposures to ionizing radiation at low doses have long been the subject of dispute. In this paper we focus on open questions regarding the health effects of low-dose exposures that require further investigations. Seemingly contradictory findings of radiation health effects have been reported for the same exposed populations, or inconsistent estimates of radiation risks were found when different populations and exposure conditions were compared. Such discrepancies may be indicative of differences in sensitivities among the applied methods of epidemiological analysis or indicative of significant discrepancies in health consequences after comparable total exposures of different populations under varying conditions. We focus first on inconsistencies and contradictions in presentations of the state of knowledge by different authoritative experts. We then review studies that found positive associations between exposure and risks in dose ranges where traditional notions (generalized primarily from high-dose studies of A-bomb survivors or exposed animals) would have predicted negligible effects. One persistent notion in many reviews of low-dose effects is the hypothesis of reduced biological effectiveness of fractionated low-dose exposures, compared to that of the same acute dose. This assumption is not supported by data on human populations. From studies of populations that live in contaminated areas, more and more evidence is accumulating on unusual rates of various diseases other than radiation-induced malignancies, health effects that are suspected to be associated with relatively low levels of internal exposures originating from radioactive fallout. Such effects include congenital defects, neonatal mortality, stillbirths, and possibly genetically transmitted disease. A range of open questions challenges scientists to test imaginative hypotheses about induction of disease by radiation with novel research strategies. Images Figure 1. PMID

  18. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    SciTech Connect

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  19. Proteomic-based mechanistic investigation of low-dose radiation-induced cellular responses/effects

    SciTech Connect

    Chen, Xian

    2013-10-23

    The goal of our project is to apply our unique systems investigation strategy to reveal the molecular mechanisms underlying the radiation induction and transmission of oxidative damage, adaptive response, and bystander effect at low-doses. Beginning with simple in vitro systems such as fibroblast or epithelial pure culture, our amino acid-coded mass tagging (AACT) comparative proteomic platform will be used to measure quantitatively proteomic changes at high- or low-dose level with respect to their endogenous damage levels respectively, in which a broad range of unique regulated proteins sensitive to low-dose IR will be distinguished. To zoom in how these regulated proteins interact with other in the form of networks in induction/transmission pathways, these regulated proteins will be selected as baits for making a series of fibroblast cell lines that stably express each of them. Using our newly developed method of ?dual-tagging? quantitative proteomics that integrate the capabilities of natural complex expression/formation, simple epitope affinity isolation (not through tandem affinity purification or TAP), and ?in-spectra? AACT quantitative measurements using mass spectrometry (MS), we will be able to distinguish systematically interacting proteins with each bait in real time. Further, in addition to both proteome-wide (global differentially expressed proteins) and pathway-scale (bait-specific) profiling information, we will perform a computational network analysis to elucidate a global pathway/mechanisms underlying cellular responses to real-time low-dose IR. Similarly, we will extend our scheme to investigate systematically those induction/transmission pathways occurring in a fibroblast-epithelial interacting model in which the bystander cell (fibroblast) monitor the IR damage to the target cell (epithelial cell). The results will provide the proteome base (molecular mechanisms/pathways for signaling) for the low dose radiation-induced essential tissue

  20. Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris

    SciTech Connect

    Stark, Karolina; Scott, David E.; Tsyusko, Olga; Coughlin, Daniel P.; Hinton, Thomas G.; Amendola, Roberto

    2015-04-30

    Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d⁻¹, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d⁻¹ and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.

  1. Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization Radiation

    PubMed Central

    Zhao, Yuchao; Ricci, Paolo F.

    2010-01-01

    For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model at very low doses is the default used by a number of national and international organizations and in regulatory law. This default denies any positive benefit from any level of exposure. However, experimental observations and theoretical biology have found that both linear and J-shaped IR dose-response curves can exist at those very low doses. We develop low dose J-shaped dose-response, based on systems biology, and thus justify its use regarding exposure to IR. This approach incorporates detailed, molecular and cellular descriptions of biological/toxicological mechanisms to develop a dose-response model through a set of nonlinear, differential equations describing the signaling pathways and biochemical mechanisms of cell cycle checkpoint, apoptosis, and tumor incidence due to IR. This approach yields a J-shaped dose response curve while showing where LNT behaviors are likely to occur. The results confirm the hypothesis of the J-shaped dose response curve: the main reason is that, at low-doses of IR, cells stimulate protective systems through a longer cell arrest time per unit of IR dose. We suggest that the policy implications of this approach are an increasingly correct way to deal with precautionary measures in public health. PMID:21191485

  2. Resource Letter EIRLD-1: Effects of ionizing radiation at low doses

    NASA Astrophysics Data System (ADS)

    Wilson, Richard

    1999-05-01

    This Resource Letter provides a guide to the literature on the effects of ionizing radiation on people at low doses. Journal articles, books, and web pages are provided for the following: data at high dose levels, effects of moderate to high doses (leukemia, solid cancer, lung cancer, childhood cancer and noncancer outcomes), effects of dose rate, relationship to background, supra linearity and homesis, and policy implications.

  3. Resource Letter EIRLD-2: Effects of Ionizing Radiation at Low Doses

    NASA Astrophysics Data System (ADS)

    Wilson, Richard

    2012-04-01

    This Resource Letter provides a guide to the literature on the effects of ionizing radiation on people at low doses. Journal articles, books and web pages are provided for the following: data at high dose levels, effects of moderate to high doses (leukemia, solid cancer, lung cancer, childhood cancer, and non-cancer outcomes), effects of dose rate, relationship to background, supra linearity and hormesis, and policy implications.

  4. Data Integration Reveals Key Homeostatic Mechanisms Following Low Dose Radiation Exposure

    SciTech Connect

    Tilton, Susan C.; Matzke, Melissa M.; Sowa, Marianne B.; Stenoien, David L.; Weber, Thomas J.; Morgan, William F.; Waters, Katrina M.

    2015-05-01

    The goal of this study was to define pathways regulated by low dose radiation to understand how biological systems respond to subtle perturbations in their environment and prioritize pathways for human health assessment. Using an in vitro 3-D human full thickness skin model, we have examined the temporal response of dermal and epidermal layers to 10 cGy X-ray using transcriptomic, proteomic, phosphoproteomic and metabolomic platforms. Bioinformatics analysis of each dataset independently revealed potential signaling mechanisms affected by low dose radiation, and integrating data shed additional insight into the mechanisms regulating low dose responses in human tissue. We examined direct interactions among datasets (top down approach) and defined several hubs as significant regulators, including transcription factors (YY1, MYC and CREB1), kinases (CDK2, PLK1) and a protease (MMP2). These data indicate a shift in response across time - with an increase in DNA repair, tissue remodeling and repression of cell proliferation acutely (24 – 72 hr). Pathway-based integration (bottom up approach) identified common molecular and pathway responses to low dose radiation, including oxidative stress, nitric oxide signaling and transcriptional regulation through the SP1 factor that would not have been identified by the individual data sets. Significant regulation of key downstream metabolites of nitrative stress were measured within these pathways. Among the features identified in our study, the regulation of MMP2 and SP1 were experimentally validated. Our results demonstrate the advantage of data integration to broadly define the pathways and networks that represent the mechanisms by which complex biological systems respond to perturbation.

  5. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    SciTech Connect

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information

  6. Nuclear Energy and Health: And the Benefits of Low-Dose Radiation Hormesis

    PubMed Central

    Cuttler, Jerry M.; Pollycove, Myron

    2009-01-01

    Energy needs worldwide are expected to increase for the foreseeable future, but fuel supplies are limited. Nuclear reactors could supply much of the energy demand in a safe, sustainable manner were it not for fear of potential releases of radioactivity. Such releases would likely deliver a low dose or dose rate of radiation, within the range of naturally occurring radiation, to which life is already accustomed. The key areas of concern are discussed. Studies of actual health effects, especially thyroid cancers, following exposures are assessed. Radiation hormesis is explained, pointing out that beneficial effects are expected following a low dose or dose rate because protective responses against stresses are stimulated. The notions that no amount of radiation is small enough to be harmless and that a nuclear accident could kill hundreds of thousands are challenged in light of experience: more than a century with radiation and six decades with reactors. If nuclear energy is to play a significant role in meeting future needs, regulatory authorities must examine the scientific evidence and communicate the real health effects of nuclear radiation. Negative images and implications of health risks derived by unscientific extrapolations of harmful effects of high doses must be dispelled. PMID:19343116

  7. Nuclear energy and health: and the benefits of low-dose radiation hormesis.

    PubMed

    Cuttler, Jerry M; Pollycove, Myron

    2009-01-01

    Energy needs worldwide are expected to increase for the foreseeable future, but fuel supplies are limited. Nuclear reactors could supply much of the energy demand in a safe, sustainable manner were it not for fear of potential releases of radioactivity. Such releases would likely deliver a low dose or dose rate of radiation, within the range of naturally occurring radiation, to which life is already accustomed. The key areas of concern are discussed. Studies of actual health effects, especially thyroid cancers, following exposures are assessed. Radiation hormesis is explained, pointing out that beneficial effects are expected following a low dose or dose rate because protective responses against stresses are stimulated. The notions that no amount of radiation is small enough to be harmless and that a nuclear accident could kill hundreds of thousands are challenged in light of experience: more than a century with radiation and six decades with reactors. If nuclear energy is to play a significant role in meeting future needs, regulatory authorities must examine the scientific evidence and communicate the real health effects of nuclear radiation. Negative images and implications of health risks derived by unscientific extrapolations of harmful effects of high doses must be dispelled.

  8. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation.

    PubMed

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-12-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts.

  9. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation

    PubMed Central

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-01-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts. PMID:26633443

  10. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation.

    PubMed

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-12-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts. PMID:26633443

  11. Effects of chronic low-dose cadmium exposure on selected biochemical and antioxidant parameters in rats.

    PubMed

    Lovásová, Eva; Rácz, Oliver; Cimboláková, Iveta; Nováková, Jaroslava; Dombrovský, Peter; Ništiar, František

    2013-01-01

    The effects of long-term (1 yr) exposure to low doses of cadmium (Cd) dissolved in drinking water on selected biochemical and antioxidant parameters were studied in Wistar rats. Rats were divided into four groups: male control group (C-m), female control group (C-f), male Cd-exposed group (Cd-m), and female Cd-exposed group (Cd-f). Cd groups were exposed to Cd dissolved in drinking water (cadmium dichloride 4.8 mg CdCl2/L, i.e., 2.5 mg Cd/L, 500-fold of maximal allowable concentration for potable water). The experiment was terminated on d 370. In all groups, biochemical parameters (total protein [TP], albumin, alanine aminotransferase, aspartate aminotransferase, glucose, cholesterol, triacylglycerols, urea, and creatinine) and antioxidant parameters (glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) were measured in the blood. Total protein and albumin concentrations were decreased significantly in the Cd-m group. Other biochemical parameters did not change in Cd groups compared to control groups. Superoxide dismutase fell significantly in both male and female Cd-exposed groups. Activity of glutathione peroxidase was markedly lower in Cd-exposed groups. Total antioxidant capacity increased significantly in Cd-f group. These results suggest that chronic low-dose oral Cd exposure induces oxidative stress. PMID:24168039

  12. The effects of chronic low-dose capsaicin treatment on substance P levels.

    PubMed

    Erin, Nuray; Zik, Berrin; Sarigül, Münevver; Tütüncü, Serife

    2009-02-25

    Capsaicin, the pungent ingredient of red pepper, is consumed in varying amounts by many ethnic groups. It serves both therapeutically and as a specific tool to investigate sensory neurons. Although effects of high capsaicin doses are well-established, systemic effects of chronic low-dose capsaicin exposure are unknown. Sprague-Dawley rats (21-day old) were injected with capsaicin (0.5 mg/kg, ip) for 6 and 19 days. Changes in Substance P (SP) levels of lung and skin were measured. Two-step sequential acetic acid extraction was used to estimate neuronal and non-neuronal SP. Six-day, but not 19-day capsaicin treatment decreased SP levels in first as well as second extractions of both tissues. Because the cumulative dose used here was much lower than the neurotoxic doses of capsaicin, initial decrease of SP levels must be due to continuous release of SP from nerve endings as well as non-neuronal tissues. The fact that SP levels returned to control values at the end of 19-day treatment demonstrates that reactive increases in SP synthesis occurred. These findings suggest that systemic exposure to low-dose capsaicin enhances sensory nerve function and also increases SP in non-neuronal tissues. In addition, significantly decreased SP levels of both tissues were observed in 40-day, compared to 27-day old rats.

  13. The effects of low doses of ionizing radiation - A question of ethics

    SciTech Connect

    Tschaeche, A.N.

    1996-12-31

    Three ethical questions are asked and answered about the current state of affairs concerning how those in power manipulate public understanding of the effects of low doses of ionizing radiation. The questions are as follows: (1) Is it ethical to frighten people when you do not know that there is anything to be frightened of? (2) Is it ethical to be so conservative that resources are spent to solve a problem that may not exist? (3) Is it ethical not to tell the whole truth about the effects of low levels of ionizing radiation?

  14. Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro

    PubMed Central

    SCHERZAD, AGMAL; HACKENBERG, STEPHAN; FROELICH, KATRIN; RAK, KRISTEN; HAGEN, RUDOLF; TAEGER, JOHANNES; BREGENZER, MAXIMILLIAN; KLEINSASSER, NORBERT

    2016-01-01

    Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induces genotoxic effects. Bone marrow MSC were treated with low-dose salinomycin (100 nM) (MSC-Sal) for 4 weeks, while the medium containing salinomycin was changed every other day. Functional changes were evaluated and compared to MSC without salinomycin treatment (MSC-control). MSC-Sal and MSC-control were positive for cluster of differentiation 90 (CD90), CD73 and CD44, and negative for CD34. There were no differences observed in cell morphology or cytoskeletal structures following salinomycin exposure. The differentiation into adipocytes and osteocytes was not counteracted by salinomycin, and proliferation capability was not inhibited following salinomycin exposure. The migration of MSC-Sal was attenuated significantly as compared to the MSC-control. There were no genotoxic effects after 4 weeks of salinomycin exposure. The present study shows an altered migration capacity as a sign of functional impairment of MSC induced by chronic salinomycin exposure. Further in vitro toxicological investigations, particularly with primary human cells, are required to understand the impact of chronic salinomycin consumption on human cell systems. PMID:26998269

  15. Mechanisms of Low Dose Radiation-induced T helper Cell Function

    SciTech Connect

    Gridley, Daila S.

    2008-10-31

    Exposure to radiation above levels normally encountered on Earth can occur during wartime, accidents such as those at Three Mile Island and Chernobyl, and detonation of “dirty bombs” by terrorists. Relatively high levels of radiation exposure can also occur in certain occupations (low-level waste sites, nuclear power plants, nuclear medicine facilities, airline industry, and space agencies). Depression or dysfunction of the highly radiosensitive cells of the immune system can lead to serious consequences, including increased risk for infections, cancer, hypersensitivity reactions, poor wound healing, and other pathologies. The focus of this research was on the T helper (Th) subset of lymphocytes that secrete cytokines (proteins), and thus control many actions and interactions of other cell types that make up what is collectively known as the immune system. The Department of Energy (DOE) Low Dose Radiation Program is concerned with mechanisms altered by exposure to high energy photons (x- and gamma-rays), protons and electrons. This study compared, for the first time, the low-dose effects of two of these radiation forms, photons and protons, on the response of Th cells, as well as other cell types with which they communicate. The research provided insights regarding gene expression patterns and capacity to secrete potent immunostimulatory and immunosuppressive cytokines, some of which are implicated in pathophysiological processes. Furthermore, the photon versus proton comparison was important not only to healthy individuals who may be exposed, but also to patients undergoing radiotherapy, since many medical centers in the United States, as well as worldwide, are now building proton accelerators. The overall hypothesis of this study was that whole-body exposure to low-dose photons (gamma-rays) will alter CD4+ Th cell function. We further proposed that exposure to low-dose proton radiation will induce a different pattern of gene and functional changes compared to

  16. Radiation-induced apoptosis in SCID Mousespleen after a low-dose irration

    NASA Astrophysics Data System (ADS)

    Ohnishi, T.; Takahashi, A.; Ohnishi, K.

    Purpose: To estimate the effects of space radiation on health of space crews, we aimed to clarify whether pre-irradiation at a low-dose interferes in a p53-centered signal transduction pathway induced by radiation. By using a severe combined immunodeficiency (Scid) mouse defective DNA-PK activity, we examined the role of DNA-PK activity in radioadaptation induced by low-dose irradiation. Methodology: Specific pathogen free 5-week-old fe male mice of Scid and the parental mice (CB-17 Icr+/+) were irradiated with X-rays at 3.0 Gy 1, 2, 3 or 4 weeks after conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after irradiation. Bax on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method using HISTOFINE SAB-PO(R) kit (Nichirei Co., Tokyo, Japan). Apoptosis incidence in the sections was measured by staining with HE staining. Results: The frequency of Bax- and apoptosis -positive cells increased up to 12 h after irradiation at 3.0 Gy in the spleen of CB-17 Icr+/+ and Scid mice. However, they were not observed by irradiation with low dose at 0.15-0.60 Gy. When pre-irradiation at 0.45 Gy 2 weeks before challenging acute irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by irradiation at 3.0 Gy was depressed in the spleen of CB-17 Icr+/+ mice, but not Scid mice. Conclusions: These data suggest that DNA-PKcs (expressed in CB-17 Icr+/+, not Scid mice) might play a major role on radioadaptation induced by pre-irradiation at low dose in mice spleen. We expect that the present findings will provide useful information for the care of space crews' health.

  17. Low-Dose Neoadjuvant External Beam Radiation Therapy for Soft Tissue Sarcoma

    SciTech Connect

    Devisetty, Kiran; Kobayashi, Wendy; Suit, Herman D.; Goldberg, Saveli I.; Niemierko, Andrzej; Chen, Yen-Lin E.; Raskin, Kevin A.; Schwab, Joseph H.; Springfield, Dempsey S.; Yoon, Sam S.; Hornicek, Francis J.; DeLaney, Thomas F.

    2011-07-01

    Purpose: For soft tissue sarcoma, neoadjuvant external beam radiation therapy (EBRT) to 50 Gy has the same local control (LC) and overall survival as postoperative radiation therapy (PORT) to 60 Gy, but with increased wound complications. We examined whether low-dose neoadjuvant EBRT would decrease acute toxicity while maintaining LC. Methods and Materials: From 1971 to 2008, 1,765 patients with nonmetastatic soft tissue sarcoma were treated with radiation therapy at Massachusetts General Hospital. We identified 42 patients treated with low-dose neoadjuvant EBRT (median, 20 Gy; range, 16-26) followed by surgical resection and PORT. PORT included EBRT (25 patients; median, 40 Gy; range, 20-56.2), brachytherapy (13 patients; median, 42 Gy; range, 26-50), and intraoperative radiation therapy (IORT) (4 patients; median, 12.5 Gy; range, 8-20). The median total dose was 63.3 Gy (range, 28-78.4). Results: Median follow-up was 36 months (range, 4-318). Severe acute wound complications were reported in 15 patients (36%) and correlated to PORT technique (16% EBRT, 69% brachytherapy, 50% IORT, p = 0.004). The 5-year LC was 73% and correlated to PORT technique (68% EBRT, 100% brachytherapy, 50% IORT, p = 0.03) and histology (p = 0.05), with a trend to improvement if >60 Gy (p = 0.10). The 5-year overall survival was 65% and correlated to extent of resection (p < 0.001) and margin status (p < 0.001). Conclusions: Despite using low-dose neoadjuvant EBRT, we report a high rate of severe acute wound complications that was strongly associated with brachytherapy. Modification of the brachytherapy technique may decrease acute toxicity while maintaining excellent local control. Further study must be conducted before recommending broader application.

  18. Mechanisms of Enhanced Cell Killing at Low Doses: Implications for Radiation Risk

    SciTech Connect

    Dr. Peter J. Johnston; Dr. George D. Wilson

    2003-10-15

    We have shown that cell lethality actually measured after exposure to low-doses of low-LET radiation, is markedly enhanced relative to the cell lethality previously expected by extrapolation of the high-dose cell-killing response. Net cancer risk is a balance between cell transformation and cell kill and such enhanced lethality may more than compensate for transformation at low radiation doses over a least the first 10 cGy of low-LET exposure. This would lead to a non-linear, threshold, dose-risk relationship. Therefore our data imply the possibility that the adverse effects of small radiation doses (<10 cGy) could be overestimated in specific cases. It is now important to research the mechanisms underlying the phenomenon of low-dose hypersensitivity to cell killing, in order to determine whether this can be generalized to safely allow an increase in radiation exposure limits. This would have major cost-reduction implications for the whole EM program.

  19. An optimized colony forming assay for low-dose-radiation cell survival measurement

    SciTech Connect

    Zhu J.; Sutherland B.; Hu W.; Ding N.; Ye C.; Usikalu M.; Li S.; Hu B.; Zhou G.

    2011-11-01

    The aim of this study is to develop a simple and reliable method to quantify the cell survival of low-dose irradiations. Two crucial factors were considered, the same number of cells plated in each flask and an appropriate interval between cell plating and irradiation. For the former, we optimized cell harvest with trypsin, diluted cells in one container, and directly seeded cells on the bottom of flasks in a low density before irradiation. Reproducible plating efficiency was obtained. For the latter, we plated cells on the bottom of flasks and then monitored the processing of attachment, cell cycle variations, and the plating efficiency after exposure to 20 cGy of X-rays. The results showed that a period of 4.5 h to 7.5 h after plating was suitable for further treatment. In order to confirm the reliability and feasibility of our method, we also measured the survival curves of these M059K and M059J glioma cell lines by following the optimized protocol and obtained consistent results reported by others with cell sorting system. In conclusion, we successfully developed a reliable and simple way to measure the survival fractions of human cells exposed to low dose irradiation, which might be helpful for the studies on low-dose radiation biology.

  20. Cell-density dependent effects of low-dose ionizing radiation on E. coli cells.

    PubMed

    Alipov, E D; Shcheglov, V S; Sarimov, R M; Belyaev, I Ya

    2003-01-01

    The changes in genome conformational state (GCS) induced by low-dose ionizing radiation in E. coli cells were measured by the method of anomalous viscosity time dependence (AVTD) in cellular lysates. Effects of X-rays at doses 0.1 cGy--1 Gy depended on post-irradiation time. Significant relaxation of DNA loops followed by a decrease in AVTD. The time of maximum relaxation was between 5-80 min depending on the dose of irradiation. U-shaped dose response was observed with increase of AVTD in the range of 0.1-4 Gy and decrease in AVTD at higher doses. No such increase in AVTD was seen upon irradiation of cells at the beginning of cell lysis while the AVTD decrease was the same. Significant differences in the effects of X-rays and gamma-rays at the same doses were observed suggesting a strong dependence of low-dose effects on LET. Effects of 0.01 cGy gamma-rays were studied at different cell densities during irradiation. We show that the radiation-induced changes in GCS lasted longer at higher cell density as compared to lower cell density. Only small amount of cells were hit at this dose and the data suggest cell-to-cell communication in response to low-dose ionizing radiation. This prolonged effect was also observed when cells were irradiated at high cell density and diluted to low cell density immediately after irradiation. These data suggest that cell-to-cell communication occur during irradiation or within 3 min post-irradiation. The cell-density dependent response to low-dose ionizing radiation was compared with previously reported data on exposure of E. coli cells to electromagnetic fields of extremely low frequency and extremely high frequency (millimeter waves). The body of our data show that cells can communicate in response to electromagnetic fields and ionizing radiation, presumably by reemission of secondary photons in infrared-submillimeter frequency range.

  1. Noise Reduction in Low-Dose X-Ray Fluoroscopy for Image-Guided Radiation Therapy

    SciTech Connect

    Wang Jing Zhu Lei; Xing Lei

    2009-06-01

    Purpose: To improve the quality of low-dose X-ray fluoroscopic images using statistics-based restoration algorithm so that the patient fluoroscopy can be performed with reduced radiation dose. Method and Materials: Noise in the low-dose fluoroscopy was suppressed by temporal and spatial filtering. The temporal correlation among neighboring frames was considered by the Karhunen-Loeve (KL) transform (i.e., principal component analysis). After the KL transform, the selected neighboring frames of fluoroscopy were decomposed to uncorrelated and ordered principal components. For each KL component, a penalized weighted least-squares (PWLS) objective function was constructed to restore the ideal image. The penalty was chosen as anisotropic quadratic, and the penalty parameter in each KL component was inversely proportional to its corresponding eigenvalue. Smaller KL eigenvalue is associated with the KL component of lower signal-to-noise ratio (SNR), and a larger penalty parameter should be used for such KL component. The low-dose fluoroscopic images were acquired using a Varian Acuity simulator. A quality assurance phantom and an anthropomorphic chest phantom were used to evaluate the presented algorithm. Results: In the images restored by the proposed KL domain PWLS algorithm, noise is greatly suppressed, whereas fine structures are well preserved. Average improvement rate of SNR is 75% among selected regions of interest. Comparison studies with traditional techniques, such as the mean and median filters, show that the proposed algorithm is advantageous in terms of structure preservation. Conclusions: The proposed noise reduction algorithm can significantly improve the quality of low-dose X-ray fluoroscopic image and allows for dose reduction in X-ray fluoroscopy.

  2. Gel microdrop flow cytometry assay for low-dose studies of chemical and radiation cytotoxicity.

    PubMed

    Bogen, K T; Enns, L; Hall, L C; Keating, G A; Weinfeld, M; Murphy, G; Wu, R W; Panteleakos, F N

    2001-03-01

    Low-level cytotoxicity may affect low-dose dose-response relations for cancer and other endpoints. Conventional colony-forming assays are rarely sensitive enough to examine small changes in cell survival and growth. Automated image-analysis techniques are limited to ca. 10(4) cells/plate. An alternative method involves encapsulation of single proliferating cells into ca. 35-75-microm-diameter agarose gel microdrops (GMDs) that are randomly grouped, differential exposure of these groups, culture at 37 degrees C for 3-5 days, and finally GMD analysis by flow cytometry (FC) to determine the ratio of GMDs containing multiple versus single cells as a measure of clonogenic survival. This GMD/FC assay was used to examine low-dose cell killing induced by a cooked-meat mutagen/rodent-carcinogen (MeIQx) in DNA-repair-deficient/metabolically-sensitive CHO cells. Results of conventional colony-forming assays using up to 30 replicate plates indicate a shouldered, threshold-like dose-response; in contrast, those obtained using the GMD/FC assay suggest "hypersensitivity"-like nonlinearity in dose-response. The GMD/FC assay was also applied to human A549 lung cells after GMD-encapsulation and gamma radiation followed by culture for a total of 4 days, to examine survival after exposure to > or =100 cGy delivered at a relatively low dose rate (0.18 cGy/min). Dose-response for clonogenic growth was again observed to be reduced with apparent nonlinear suggesting hypersensitivity between 0 and 50 cGy, insofar as doses of 5 and 10 cGy appear to be ca. fivefold more effective per unit dose than the 50- or 100-cGy doses used. The GMD/FC assay may thus reveal low-dose dose-response relations for chemical and radiation effects on cell proliferation/killing with implications for low-dose risk assessment.

  3. A review of some epidemiological studies on cancer risk from low-dose radiation or other carcinogenic agents.

    PubMed

    Ogata, Hiromitsu

    2011-07-01

    It is extremely difficult to assess cancer risks accurately due to health effects of low-dose radiation exposure or other carcinogens based on epidemiological studies. For the detection of minute increases of the risk at low-level exposure, most of epidemiological studies lack statistical power, and they involve various complicated confounding factors. This paper reports on a literature survey of epidemiological studies published since 2000 on cancer risks associated with low-dose radiation and other carcinogens to gather major epidemiological data. Integrated risk indices were derived from those data by using, where possible, statistical models. Regarding risk assessment of low-dose radiation exposure, it is important to lower the degree of uncertainty arising from risk estimation. Risk assessment of low-dose radiation exposure could be scientific evidence when uncertainty is considered in comparing carcinogenic risks of radiation with those of other carcinogens.

  4. Review and Evaluation of Updated Research on the Health Effects Associated with Low-Dose Ionizing Radiation

    SciTech Connect

    Dauer, Lawrence T.; Brooks, Antone L.; Hoel, David G.; Morgan, William F.; Stram, Daniel; Tran, Phung

    2010-07-01

    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.

  5. Identifying the health risks from very low-dose sparsely ionizing radiation.

    PubMed Central

    Dreyer, N A; Friedlander, E

    1982-01-01

    The health risks from low-dose sparsely ionizing (low-LET) radiation have been the subject of continued debate. At present, quantitative estimates of risk are extremely uncertain due to the controversy surrounding both the dosimetry for A-bomb survivor data and the choice of mathematical models for extrapolating risk from high to low doses. Nevertheless, much can be learned about the nature of the health risks by reviewing the epidemiologic literature. We present a summary of diseases which have been associated with low-LET radiation (less than 1000 rad) in at least two independent studies, according to the mean cumulative organ dose at which the disease was observed. At organ doses of less than or equal to 50 rad, the only diseases that have been reported consistently are thyroid cancer, salivary gland tumors, and leukemia. The first two diseases were observed in association with x-ray epilation of the scalp for tinea capitis, a therapy which is no longer employed. On the other hand, leukemia has been observed repeatedly to occur at cumulative doses of greater than or equal to 30 rad low-LET radiation. PMID:7041660

  6. Methods for analyzing combined data from studies of workers exposed to low doses of radiation.

    PubMed

    Gilbert, E S; Fry, S A; Wiggs, L D; Voelz, G L; Cragle, D L; Petersen, G R

    1990-05-01

    Epidemiologic studies of workers exposed occupationally to protracted low doses of radiation provide a direct assessment of health effects resulting from such exposure and thus supplement information provided by studies of populations exposed at high doses of radiation and high dose rates. Analyses based on combined data from several studies can be expected to provide a more thorough assessment of low dose occupational studies and more precise risk estimates than can be obtained from any single study. Statistical methods for conducting such combined analyses are discussed, and different approaches, such as basing analyses on various levels of aggregation of exposure data, are compared and evaluated. Emphasis is given to methods for obtaining risk estimates and confidence limits that can be appropriately compared with estimates that form the basis for current radiation protection standards; these estimates have been obtained through extrapolation from high dose data. Methods are illustrated using combined data on workers at three US Department of Energy facilities: the Hanford Site, Richland, Washington; the Oak Ridge National Laboratory, Oak Ridge, Tennessee; and the Rocky Flats Nuclear Weapons Plant, Denver, Colorado. PMID:2321632

  7. Low-dose radiation modifies skin response to acute gamma-rays and protons.

    PubMed

    Mao, Xiao Wen; Pecaut, Michael J; Cao, Jeffrey D; Moldovan, Maria; Gridley, Daila S

    2013-01-01

    The goal of the present study was to obtain pilot data on the effects of protracted low-dose/low-dose-rate (LDR) γ-rays on the skin, both with and without acute gamma or proton irradiation (IR). Six groups of C57BL/6 mice were examined: a) 0 Gy control, b) LDR, c) Gamma, d) LDR+Gamma, e) Proton, and f) LDR+Proton. LDR radiation was delivered to a total dose of 0.01 Gy (0.03 cGy/h), whereas the Gamma and Proton groups received 2 Gy (0.9 Gy/min and 1.0 Gy/min, respectively). Assays were performed 56 days after exposure. Skin samples from all irradiated groups had activated caspase-3, indicative of apoptosis. The significant (p<0.05) increases in immunoreactivity in the Gamma and Proton groups were not present when LDR pre-exposure was included. However, the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay for DNA fragmentation and histological examination of hematoxylin and eosin-stained sections revealed no significant differences among groups, regardless of radiation regimen. The data demonstrate that caspase-3 activation initially triggered by both forms of acute radiation was greatly elevated in the skin nearly two months after whole-body exposure. In addition, LDR γ-ray priming ameliorated this response.

  8. Low-dose radiation may be a novel approach to enhance the effectiveness of cancer therapeutics.

    PubMed

    Yang, Guozi; Li, Wei; Jiang, Hongyu; Liang, Xinyue; Zhao, Yuguang; Yu, Dehai; Zhou, Lei; Wang, Guanjun; Tian, Huimin; Han, Fujun; Cai, Lu; Cui, Jiuwei

    2016-11-15

    It has been generally accepted that both natural and man-made sources of ionizing radiation contribute to human exposure and consequently pose a possible risk to human health. However, accumulating evidence has shown that the biological effects of low-dose radiation (LDR) are different from those of high-dose radiation. LDR can stimulate proliferation of normal cells and activate their defense systems, while these biological effects are not observed in some cancer cell types. Although there is still no concordance on this matter, the fact that LDR has the potential to enhance the effects of cancer therapeutics and reduce the toxic side effects of anti-cancer therapy has garnered significant interest. Here, we provide an overview of the current knowledge regarding the experimental data detailing the different responses of normal and cancer tissues to LDR, the underlying mechanisms, and its significance in clinical application. PMID:27299986

  9. Low-dose radiation may be a novel approach to enhance the effectiveness of cancer therapeutics.

    PubMed

    Yang, Guozi; Li, Wei; Jiang, Hongyu; Liang, Xinyue; Zhao, Yuguang; Yu, Dehai; Zhou, Lei; Wang, Guanjun; Tian, Huimin; Han, Fujun; Cai, Lu; Cui, Jiuwei

    2016-11-15

    It has been generally accepted that both natural and man-made sources of ionizing radiation contribute to human exposure and consequently pose a possible risk to human health. However, accumulating evidence has shown that the biological effects of low-dose radiation (LDR) are different from those of high-dose radiation. LDR can stimulate proliferation of normal cells and activate their defense systems, while these biological effects are not observed in some cancer cell types. Although there is still no concordance on this matter, the fact that LDR has the potential to enhance the effects of cancer therapeutics and reduce the toxic side effects of anti-cancer therapy has garnered significant interest. Here, we provide an overview of the current knowledge regarding the experimental data detailing the different responses of normal and cancer tissues to LDR, the underlying mechanisms, and its significance in clinical application.

  10. Choosing populations to study the health effects of low-dose ionizing radiation.

    PubMed Central

    Dreyer, N A; Loughlin, J E; Friedlander, E R; Clapp, R W; Fahey, F H

    1981-01-01

    In January 1978, the United States Congress requested information about the utility of additional epidemiologic studies for quantifying the health effects of low-dose ionizing radiation. In our judgment, no single population can be recommended for study on purely scientific grounds, since the largest group offers only a small chance to obtain a definitive result. On the other hand, if social pressures and regulatory agencies mandate that such studies be attempted, we would recommend prospective cohort studies of occupational populations. We propose that a national worker registry be developed using ionizing radiation as the prototype for studying other occupational exposures. The problems related to studying low-level radiation are not unique, but apply equally to investigations dealing with a great variety of toxic agents. A national plan for collecting information on workers' exposure and health could provide a cost-efficient means to answer public health questions posed by the Congress, scientists and the public. PMID:7294269

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

    PubMed

    Acharya, Munjal M; Patel, Neal H; Craver, Brianna M; Tran, Katherine K; Giedzinski, Erich; Tseng, Bertrand P; Parihar, Vipan K; Limoli, Charles L

    2015-01-01

    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.

  12. High and Low Doses of Ionizing Radiation Induce Different Secretome Profiles in a Human Skin Model

    SciTech Connect

    Zhang, Qibin; Matzke, Melissa M.; Schepmoes, Athena A.; Moore, Ronald J.; Webb-Robertson, Bobbie-Jo M.; Hu, Zeping; Monroe, Matthew E.; Qian, Weijun; Smith, Richard D.; Morgan, William F.

    2014-03-18

    It is postulated that secreted soluble factors are important contributors of bystander effect and adaptive responses observed in low dose ionizing radiation. Using multidimensional liquid chromatography-mass spectrometry based proteomics, we quantified the changes of skin tissue secretome – the proteins secreted from a full thickness, reconstituted 3-dimensional skin tissue model 48 hr after exposure to 3, 10 and 200 cGy of X-rays. Overall, 135 proteins showed statistical significant difference between the sham (0 cGy) and any of the irradiated groups (3, 10 or 200 cGy) on the basis of Dunnett adjusted t-test; among these, 97 proteins showed a trend of downregulation and 9 proteins showed a trend of upregulation with increasing radiation dose. In addition, there were 21 and 8 proteins observed to have irregular trends with the 10 cGy irradiated group either having the highest or the lowest level among all three radiated doses. Moreover, two proteins, carboxypeptidase E and ubiquitin carboxyl-terminal hydrolase isozyme L1 were sensitive to ionizing radiation, but relatively independent of radiation dose. Conversely, proteasome activator complex subunit 2 protein appeared to be sensitive to the dose of radiation, as rapid upregulation of this protein was observed when radiation doses were increased from 3, to 10 or 200 cGy. These results suggest that different mechanisms of action exist at the secretome level for low and high doses of ionizing radiation.

  13. Effects of Low Dose Particle Radiation to Mouse Neonatal Neurons in Culture

    NASA Astrophysics Data System (ADS)

    Nojima, K.; Vazquez, M. E.; Okayasu, R.; Nagaoka, S.

    To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions by HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05Gy up to 2.0Gy. The subsequent biological effectswere evaluated by an induction of apoptosis and neuron survival focusing on the dependencies of the animal strains, SCID, B6, B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to particle radiation as evaluated by 10% apoptotic criterion. The LET dependency was compared with using SCID and B6 cells exposing to different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency was observed in the high LET (55 -200 keV/μ m) and low dose (<0.5 Gy) regions. The survivability profiles of the neurons were different in the mouse strains and ions. In this repot, a result of memory and learning function to adult mice after whole-body and brainlocal irradiation at carbon ion and iron ion.

  14. Analysis of low-dose radiation shield effectiveness of multi-gate polymeric sheets

    NASA Astrophysics Data System (ADS)

    Kim, S. C.; Lee, H. K.; Cho, J. H.

    2014-07-01

    Computed tomography (CT) uses a high dose of radiation to create images of the body. As patients are exposed to radiation during a CT scan, the use of shielding materials becomes essential in CT scanning. This study was focused on the radiation shielding materials used for patients during a CT scan. In this study, sheets were manufactured to shield the eyes and the thyroid, the most sensitive parts of the body, against radiation exposure during a CT scan. These sheets are manufactured using silicone polymers, barium sulfate (BaSO4) and tungsten, with the aim of making these sheets equally or more effective in radiation shielding and more cost-effective than lead sheets. The use of barium sulfate drew more attention than tungsten due to its higher cost-effectiveness. The barium sulfate sheets were coated to form a multigate structure by applying the maximum charge rate during the agitator and subsequent mixing processes and creating multilayered structures on the surface. To measure radiation shielding effectiveness, the radiation dose was measured around both eyes and the thyroid gland using sheets in three different thicknesses (1, 2 and 3 mm). Among the 1 and 2 mm sheets, the Pb sheets exhibited greater effectiveness in radiation shielding around both eyes, but the W sheets were more effective in radiation shielding around the thyroid gland. In the 3 mm sheets, the Pb sheet also attenuated a higher amount of radiation around both eyes while the W sheet was more effective around the thyroid gland. In conclusion, the sheets made from barium sulfate and tungsten proved highly effective in shielding against low-dose radiation in CT scans without causing ill-health effects, unlike lead.

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

    PubMed

    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. PMID:26910032

  16. A Low-Dose Ipsilateral Lung Restriction Improves 3-D Conformal Planning for Partial Breast Radiation Therapy

    SciTech Connect

    Mitchell, Tracy; Truong, Pauline T.; Salter, Lee; Graham, Cathy; Gaffney, Helene; Beckham, Wayne; Olivotto, Ivo A.

    2011-04-01

    In trials of 3D conformal external beam partial breast radiotherapy (PBRT), the dosimetrist must balance the priorities of achieving high conformity to the target versus minimizing low-dose exposure to the normal structures. This study highlights the caveat that in the absence of a low-dose lung restriction, the use of relatively en-face fields may meet trial-defined requirements but expose the ipsilateral lung to unnecessary low-dose radiation. Adding a low-dose restriction that {<=}20% of the ipsilateral lung should receive 10% of the prescribed dose resulted in successful plans in 88% of cases. This low-dose lung limit should be used in PBRT planning.

  17. Chronic low-dose γ-irradiation of Drosophila melanogaster larvae induces gene expression changes and enhances locomotive behavior

    PubMed Central

    Kim, Cha Soon; Seong, Ki Moon; Lee, Byung Sub; Lee, In Kyung; Yang, Kwang Hee; Kim, Ji-Young; Nam, Seon Young

    2015-01-01

    Although radiation effects have been extensively studied, the biological effects of low-dose radiation (LDR) are controversial. This study investigates LDR-induced alterations in locomotive behavior and gene expression profiles of Drosophila melanogaster. We measured locomotive behavior using larval pupation height and the rapid iterative negative geotaxis (RING) assay after exposure to 0.1 Gy γ-radiation (dose rate of 16.7 mGy/h). We also observed chronic LDR effects on development (pupation and eclosion rates) and longevity (life span). To identify chronic LDR effects on gene expression, we performed whole-genome expression analysis using gene-expression microarrays, and confirmed the results using quantitative real-time PCR. The pupation height of the LDR-treated group at the first larval instar was significantly higher (∼2-fold increase in PHI value, P < 0.05). The locomotive behavior of LDR-treated male flies (∼3 − 5 weeks of age) was significantly increased by 7.7%, 29% and 138%, respectively (P < 0.01), but pupation and eclosion rates and life spans were not significantly altered. Genome-wide expression analysis identified 344 genes that were differentially expressed in irradiated larvae compared with in control larvae. We identified several genes belonging to larval behavior functional groups such as locomotion (1.1%), oxidation reduction (8.0%), and genes involved in conventional functional groups modulated by irradiation such as defense response (4.9%), and sensory and perception (2.5%). Four candidate genes were confirmed as differentially expressed genes in irradiated larvae using qRT-PCR (>2-fold change). These data suggest that LDR stimulates locomotion-related genes, and these genes can be used as potential markers for LDR. PMID:25792464

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

    PubMed

    Nishad, S; Ghosh, Anu

    2016-02-01

    Humans are continually exposed to ionizing radiation from natural as well as anthropogenic sources. Though biological effects of high dose radiation exposures have been well accepted, studies on low-to-moderate dose exposures (in the range of 50-500 mGy) have been strongly debated even as researchers continue to search for elusive 'radiation signatures' in humans. Proteins are considered as dynamic functional players that drive cellular responses. However, there is little proteomic information available in context of human exposure to ionizing radiation. In this study, we determined differential expressed proteins in G0 peripheral blood mononuclear cells (PBMCs) from healthy individuals 1h and 4h after 'ex vivo' exposure with two radiation doses (300 mGy and 1 Gy). Twenty-three proteins were found to be significantly altered in irradiated cells when compared to sham irradiated cells with fold change ± 1.5-fold (p ≤ 0.05), with only three proteins showing ≥ 2.5-fold change, either with dose or with time. Mass spectrometry analyses identified redox sensor protein, chloride intracellular channel protein 1 (CLIC-1), the antioxidant protein, peroxiredoxin-6 and the pro-survival molecular chaperone 78 KDa glucose regulated protein (GRP78) among the 23 modulated proteins. The mean coefficient of variation (CV) for the twenty-three radiation responsive protein spots was found to be 33.7% for 300 mGy and 48.3% for 1 Gy. We thus, conclude that the radiation proteomic response of G0 human PBMCs, which are in the resting stage of the cell cycle, involves moderate upregulation of protective mechanisms, with low inter-individual variability. This study will help further our understanding of cellular effects of low dose acute radiation in humans and contribute toward differential biomarker discovery. PMID:26921016

  19. Radiosensitization of Human Cervical Cancer Cells by Inhibiting Ribonucleotide Reductase: Enhanced Radiation Response at Low-Dose Rates

    SciTech Connect

    Kunos, Charles A.; Colussi, Valdir C.; Pink, John; Radivoyevitch, Tomas; Oleinick, Nancy L.

    2011-07-15

    Purpose: To test whether pharmacologic inhibition of ribonucleotide reductase (RNR) by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC no. 663249) enhances radiation sensitivity during low-dose-rate ionizing radiation provided by a novel purpose-built iridium-192 cell irradiator. Methods and Materials: The cells were exposed to low-dose-rate radiation (11, 23, 37, 67 cGy/h) using a custom-fabricated cell irradiator or to high-dose-rate radiation (330 cGy/min) using a conventional cell irradiator. The radiation sensitivity of human cervical (CaSki, C33-a) cancer cells with or without RNR inhibition by 3-AP was evaluated using a clonogenic survival and an RNR activity assay. Alteration in the cell cycle distribution was monitored using flow cytometry. Results: Increasing radiation sensitivity of both CaSki and C33-a cells was observed with the incremental increase in radiation dose rates. 3-AP treatment led to enhanced radiation sensitivity in both cell lines, eliminating differences in cell cytotoxicity from the radiation dose rate. RNR blockade by 3-AP during low-dose-rate irradiation was associated with low RNR activity and extended G{sub 1}-phase cell cycle arrest. Conclusions: We conclude that RNR inhibition by 3-AP impedes DNA damage repair mechanisms that rely on deoxyribonucleotide production and thereby increases radiation sensitivity of human cervical cancers to low-dose-rate radiation.

  20. [The low doses of radiation: Towards a new reading of the risk assessment].

    PubMed

    Perez, Anne-Fleur; Devic, Clément; Colin, Catherine; Foray, Nicolas

    2015-06-01

    From Hiroshima bomb explosion data, the risk of radiation-induced cancer is significant from 100 mSv for a population considered as uniform and radioresistant. However, the recent radiobiological data bring some new elements that highlight some features that were not taken into account: the individual factor, the dose rate and the repeated dose effect. The objective evaluation of the cancer risk due to doses lower than 100 mSv is conditioned by high levels of measurability and statistical significance. However, it appears that methodological rigor is not systematically applied in all the papers. Furthermore, unclear communication in press often leads to some announcement effects, which does not improve the readability of the issue. This papers aims to better understand the complexity of the low-dose-specific phenomena as a whole, by confronting the recent biological data with epidemiological data. PMID:25959519

  1. Characterization of the role of Fhit in maintenance of genomic integrity following low dose radiation, in vivo and in vitro

    SciTech Connect

    Wang, Ya

    2010-05-14

    The major goal of this study is to determine the effects of the Fhit pathway on low dose (< 0.1 Gy) ionizing radiation (IR)-induced genetic instability. Reduction of Fhit protein expression is observed in most solid tumors particularly in those tumors resulting from exposure to environmental carcinogens. Therefore, characterization of the role of the Fhit-dependent pathway in preventing low dose IR-induced genetic instability will provide useful parameters for evaluating the low dose IR-induced risk of mutagenesis and carcinogenesis. We pursued 3 specific aims to study our hypothesis that the Fhit-dependent pathways maintain genomic integrity through adjusting checkpoint response and repair genes expression following low dose IR. Aim 1: Determine whether Fhit interaction with RPA is necessary for Fhit to affect the cellular response to low dose IR. We combined the approaches of in vitro (GST pull-down and site-directed mutagenesis) and in vivo (observing the co-localization and immunoprecipitation of Fhit and RPA in Fhit knock out mouse cells transfected with mutant Fhit which has lost ability to interact with RPA in vitro). Aim 2: Determine the role of genes whose expression is affected by Fhit in low dose irradiated cells. We analyzed the distinct signature of gene expression in low dose irradiated Fhit-/- cells compared with Fhit+/+ cells by combining microarray, gene transfection and siRNA approaches. Aim 3: Determine the role of Fhit in genetic susceptibility to low dose IR in vivo. We compared the gene mutation frequency and the fragile site stability in the cells isolated from the Fhit+/+ and Fhit-/- mice at 1.5 years following low dose IR. These results determine the role of the Fhit-dependent pathway in maintaining genomic integrity in vitro and in vivo, which provide a basis for choosing surrogate markers in the Fhit-dependent pathway to evaluate low dose IR-induced risk of mutagenesis and carcinogenesis.

  2. Characterization of the role of Fhit in maintenance of genomic integrity following low dose radiation, in vivo and in vitro

    SciTech Connect

    Ya Wang

    2010-05-31

    The major goal of this study is to determine the effects of the Fhit pathway on low dose ({le} 0.1 Gy) ionizing radiation (IR)-induced genetic instability. Reduction of Fhit protein expression is observed in most solid tumors particularly in those tumors resulting from exposure to environmental carcinogens. Therefore, characterization of the role of the Fhit-dependent pathway in preventing low dose IR-induced genetic instability will provide useful parameters for evaluating the low dose IR-induced risk of mutagenesis and carcinogenesis. We pursued 3 specific aims to study our hypothesis that the Fhit-dependent pathways maintain genomic integrity through adjusting checkpoint response and repair genes expression following low dose IR. Aim 1: Determine whether Fhit interaction with RPA is necessary for Fhit to affect the cellular response to low dose IR. We combined the approaches of in vitro (GST pull-down and site-directed mutagenesis) and in vivo (observing the co-localization and immunoprecipitation of Fhit and RPA in Fhit knock out mouse cells transfected with mutant Fhit which has lost ability to interact with RPA in vitro). Aim 2: Determine the role of genes whose expression is affected by Fhit in low dose irradiated cells. We analyzed the distinct signature of gene expression in low dose irradiated Fhit-/- cells compared with Fhit+/+ cells by combining microarray, gene transfection and siRNA approaches. Aim 3: Determine the role of Fhit in genetic susceptibility to low dose IR in vivo. We compared the gene mutation frequency and the fragile site stability in the cells isolated from the Fhit+/+ and Fhit-/- mice at 1.5 years following low dose IR. These results determine the role of the Fhit-dependent pathway in maintaining genomic integrity in vitro and in vivo, which provide a basis for choosing surrogate markers in the Fhit-dependent pathway to evaluate low dose IR-induced risk of mutagenesis and carcinogenesis.

  3. Low dose detection of γ radiation via solvent assisted fluorescence quenching.

    PubMed

    Han, Ji-Min; Xu, Miao; Wang, Brian; Wu, Na; Yang, Xiaomei; Yang, Haori; Salter, Bill J; Zang, Ling

    2014-04-01

    Development of low cost, easy-to-use chemical sensor systems for low dose detection of γ radiation remains highly desired for medical radiation therapy and nuclear security monitoring. We report herein on a new fluorescence sensor molecule, 4,4'-di(1H-phenanthro[9,10-d]imidazol-2-yl)biphenyl (DPI-BP), which can be dissolved into halogenated solvents (e.g., CHCl3, CH2Cl2) to enable instant detection of γ radiation down to the 0.01 Gy level. The sensing mechanism is primarily based on radiation induced fluorescence quenching of DPI-BP. Pristine DPI-BP is strongly fluorescent in halogenated solvents. When exposed to γ radiation, the halogenated solvents decompose into various radicals, including hydrogen and chlorine, which then combine to produce hydrochloric acid (HCl). This strong acid interacts with the imidazole group of DPI-BP to convert it into a DPI-BP/HCl adduct. The DPI-BP/HCl adduct possesses a more planar configuration than DPI-BP, enhancing the π-π stacking and thus molecular aggregation. The strong molecular fluorescence of DPI-BP gets quenched upon aggregation, due to the π-π stacking interaction (forming forbidden low-energy excitonic transition). Interestingly the quenched fluorescence can be recovered simply by adding base (e.g., NaOH) into the solution to dissociate the DPI-BP/HCl adduct. Such sensing mechanism was supported by systematic investigations based on HCl titration and dynamic light scattering measurements. To further confirm that the aggregation caused fluorescence quenching, a half size analogue of DPI-BP, 2-phenyl-1H-phenanthro[9,10-d]imidazole (PI-Ph), was synthesized and investigated in comparison with the observations of DPI-BP. PI-Ph shares the same imidazole conjugation structure with DPI-BP and is expected to bind the same way with HCl. However, PI-Ph did not show fluorescence quenching upon binding with HCl likely due to the smaller π-conjugation structure, which can hardly enforce the π-π stacking assembly. Combining

  4. MOLECULAR MECHANISM OF SUPPRESSION OF NEOPLASTIC TRANSFORMATION BY LOW DOSES OF LOW LET RADIATION

    SciTech Connect

    J.LESIE REDPATH, PH.D.

    2011-03-29

    We are currently funded (9/01-8/04) by the DOE Low Dose Radiation Research Program to examine mechanisms underlying the suppression of neoplastic transformation in vitro by low doses of low LET radiation. For the new studies proposed under Notice 04-21, we intend to follow up on our observation that upregulation of DNA repair may be an important factor and that its importance is dose-dependent. The experimental system will be the human hybrid cell neoplastic transformation assay that we are currently using. We propose to test the following hypothesis: Down-regulation of DNA dsb repair will abrogate the low dose suppression of neoplastic transformation. Using the technique of RNA silencing, it is proposed to test the effect of down-regulation of the two major DNA dsb repair pathways, homologous recombination (HR) and non-homologous end-joining (NHEJ), on the dose response relationship for neoplastic transformation. Based on prior studies, we predict that this will result in abrogation of the suppressive effect at doses in the range 1 to 10 cGy, but not at lower doses. The proposed experiments will also help address the question as to which of the two DNA repair pathways may be the most important in causing suppression of transformation. HR is a pathway that is predominant in S and G2 phase cells and is known to be less error-prone than the NHEJ pathway that is predominant in G1 phase. We hypothesize that down-regulation of HR will result in the most effective abrogation of suppression. An important component of this study will be the determination of the how abrogation of DNA dsb repair impacts the spontaneous transformation frequency, presumably a consequence of endogeneous DNA damage. Experiments will be carried out using partially synchronized populations of cells enriched for G1 and S/G2 respectively. In addition to the endpoint of neoplastic transformation the impact of down-regulation of HR and NHEJ on the formation and disappearance of the DNA dsb marker

  5. Using Drosophila Larval Imaginal Discs to Study Low-Dose Radiation-Induced Cell Cycle Arrest

    PubMed Central

    Yan, Shian-Jang; Li, Willis X.

    2012-01-01

    Under genotoxic stress, activation of cell cycle checkpoint responses leads to cell cycle arrest, which allows cells to repair DNA damage before continuing to cycle. Drosophila larval epithelial sacs, called imaginal discs, are an excellent in vivo model system for studying radiation-induced cell cycle arrest. Larval imaginal discs go into cell cycle arrest after being subjected to low-dose irradiation, are subject to easy genetic manipulation, are not crucial for survival of the organism, and can be dissected easily for further molecular or cellular analysis. In this chapter, we describe methods for assessing low-dose irradiation-induced cell cycle arrest. Mitotic cells are identified by immunofluorescence staining for the mitotic marker phosphorylated histone H3 (phospho-histone H3 or pH3). When wandering third-instar control larvae, without transgene expression, are exposed to 500 rads of X-ray or γ-ray irradiation, the number of pH3-positive cells in wing imaginal discs is reduced from hundreds before irradiation to approximately 30 after irradiation, with an equal distribution between the anterior and posterior compartments (Yan et al., 2011, FASEB J). Using the GAL4/UAS system, RNAi, cDNA, or microRNA sponge transgenes can be expressed in the posterior compartment of the wing disc using drivers such as engrailed (en)-Gal4, while the anterior compartment serves as an internal control. This approach makes it possible to do genome-wide genetic screening for molecules involved in radiation-induced cell cycle arrest. PMID:21870287

  6. Single-ion microbeam as a tool for low-dose radiation effects investigations

    NASA Astrophysics Data System (ADS)

    Gerardi, Silvia; Galeazzi, Giuseppe; Cherubini, Roberto

    2006-05-01

    Practical assessment of human radiation exposure risk deserves particular attention especially for low doses (and low dose rates), which concern environmental and occupational exposure. At these dose levels ionizing radiation exposures involve mainly isolated charged particle tracks, which strike individual cells at time intervals averaging from weeks to several years apart. Accelerator-based microbeam irradiation technique offers a unique tool to mimic such an exposure, allowing irradiating single cells individually with micrometer precision and with a preset number of charged particles down to one particle per cell. A horizontal single-ion microbeam facility for single-cell irradiations has been designed and set up at the INFN-LNL 7MV CN Van de Graaff accelerator. The light ion beam is collimated in air down to a section of 2-3µm in diameter by means of appropriate pinholes. Semi-automatic cell visualization and automatic cell positioning and revisiting system, based on an inverted phase contrast optical microscope and on X-Y translation stages with 0.1µm positioning precision, has been developed. An in-house-written software allows to control remotely the irradiation protocol. As a distinctive feature of the facility, cell recognition is performed without using fluorescent staining and UV light. Particle detection in air, behind the biological sample, is based on a silicon detector while in-air beam profile and precise hit position measurements are accomplished by a custom-made cooled-CCD camera and Solid State Nuclear Track detectors, respectively. A particle counting rate of less than 1 ion/sec can be reached.

  7. Survey on low-dose medical radiation exposure in occupational workers: the effect on hematological change

    NASA Astrophysics Data System (ADS)

    Ryu, J. K.; Cho, S. M.; Cho, J. H.; Dong, K. R.; Chung, W. K.; Lee, J. W.

    2013-03-01

    This study examined the changes in the hematological index caused by low-dose medical radiation exposure in workers in a medical radiation-exposed environment. The cumulative dose was obtained using thermoluminescent dosimeters over a 9-year period, and the changes in hematological index count (red blood cells (RBCs), hemoglobin, platelets, white blood cells (WBCs), monocytes, lymphocytes, neutrophils, basophils, and eosinophils) were examined in both the occupational workers and controls. In total, 370 occupational workers and 335 controls were compared. The analysis led to the following observations: (1) The average cumulative dose in males and females was 9.65±15.2 and 4.82±5.55 mSv, respectively. (2) In both males and females, there was a very low correlation between the occupation period and the cumulative dose (r<±0.25). (3) When the occupation period was longer, the WBC counts both decreased and increased in the male workers and the RBC counts were lower in the workers than in the control group (p<0.05). In females, the WBC counts both decreased and increased in the workers and the eosinophil counts were lower in the workers than in the control group (p<0.01). (4) When the cumulative dose was large, the lymphocyte counts decreased in male workers and the platelet count was lower in the workers than in the control group (p<0.05). In females, the lymphocyte count and RBC count were lower in the workers than in the control group (p<0.05). Abnormal distributions of some blood indices were observed in the occupational radiation workers compared with the controls. Attempts were made to limit radiation exposure to personnel, but the employees did not always follow the preset rules. Actually, the adverse effects of low-level radiation were attributed to probability. Overall, workers should obey the radiation protection regulations provided by the government and a national system of radiation protection is needed.

  8. Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

    SciTech Connect

    Jirtle, Randy L.

    2012-10-11

    The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (A{sup vy}) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure (<10 cGy) during early gestation. This information is particularly important to ascertain given the increased use of CT scans in disease diagnosis, increased number of people predicted to live and work in space, and the present concern about radiological terrorism. We showed for the first time that LDIR significantly increased DNA methylation at the A{sup vy} locus in a sex-specific manner (p=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic Avy mouse model epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in

  9. Low dose radiation hypersensitivity and clustered DNA damages in human fibroblasts exposed to low dose and dose rate protons or 137CS y-rays

    SciTech Connect

    Bennett P. V.; Bennett, P.V.; Keszenman, D.J.; Johnson, A.M.; Sutherland, B.M.; Wilson, P.F.

    2013-05-14

    Effective radioprotection for human space travelers hinges upon understanding the individual properties of charged particles. A significant fraction of particle radiation astronauts will encounter in space exploratory missions will come from high energy protons in galactic cosmic radiation (GCR) and/or possible exposures to lower energy proton flux from solar particle events (SPEs). These potential exposures present major concerns for NASA and others, in planning and executing long term space exploratory missions. We recently reported cell survival and transformation (acquisition of anchorage-independent growth in soft agar) frequencies in apparently normal NFF-28 primary human fibroblasts exposed to 0-30 cGy of 50MeV, 100MeV (SPE-like), or 1000 MeV (GCR-like) monoenergetic protons. These were modeled after 1989 SPE energies at an SPE-like low dose-rate (LDR) of 1.65 cGy/min or high dose rate (HDR) of 33.3 cGy/min delivered at the NASA Space Radiation Laboratory (NSRL) at BNL.

  10. Low-dose ionizing radiation induces mitochondrial fusion and increases expression of mitochondrial complexes I and III in hippocampal neurons

    PubMed Central

    Chang, Chuang-Rung; Kao, Mou-Chieh; Chen, Kuan-Wei; Chiu, Shih-Che; Hsu, Ming-Ling; Hsiang, I-Chou; Chen, Yu-Jen; Chen, Linyi

    2015-01-01

    High energy ionizing radiation can cause DNA damage and cell death. During clinical radiation therapy, the radiation dose could range from 15 to 60 Gy depending on targets. While 2 Gy radiation has been shown to cause cancer cell death, studies also suggest a protective potential by low dose radiation. In this study, we examined the effect of 0.2-2 Gy radiation on hippocampal neurons. Low dose 0.2 Gy radiation treatment increased the levels of MTT. Since hippocampal neurons are post-mitotic, this result reveals a possibility that 0.2 Gy irradiation may increase mitochondrial activity to cope with stimuli. Maintaining neural plasticity is an energy-demanding process that requires high efficient mitochondrial function. We thus hypothesized that low dose radiation may regulate mitochondrial dynamics and function to ensure survival of neurons. Our results showed that five days after 0.2 Gy irradiation, no obvious changes on neuronal survival, neuronal synapses, membrane potential of mitochondria, reactive oxygen species levels, and mitochondrial DNA copy numbers. Interestingly, 0.2 Gy irradiation promoted the mitochondria fusion, resulting in part from the increased level of a mitochondrial fusion protein, Mfn2, and inhibition of Drp1 fission protein trafficking to the mitochondria. Accompanying with the increased mitochondrial fusion, the expressions of complexes I and III of the electron transport chain were also increased. These findings suggest that, hippocampal neurons undergo increased mitochondrial fusion to modulate cellular activity as an adaptive mechanism in response to low dose radiation. PMID:26415228

  11. Low-Dose, Ionizing Radiation and Age-Related Changes in Skeletal Microarchitecture

    DOE PAGESBeta

    Alwood, Joshua S.; Kumar, Akhilesh; Tran, Luan H.; Wang, Angela; Limoli, Charles L.; Globus, Ruth K.

    2012-01-01

    Osteoporosis can profoundly affect the aged as a consequence of progressive bone loss; high-dose ionizing radiation can cause similar changes, although less is known about lower doses (≤100 cGy). We hypothesized that exposure to relatively low doses of gamma radiation accelerates structural changes characteristic of skeletal aging. Mice (C57BL/6J-10 wk old, male) were irradiated (total body; 0-sham, 1, 10 or 100 cGy 137 Cs) and tissues harvested on the day of irradiation, 1 or 4 months later. Microcomputed tomography was used to quantify microarchitecture of high turnover, cancellous bone. Irradiation at 100 cGy caused transient microarchitectural changes over one month that were only evidentmore » at longer times in controls (4 months). Ex vivo bone cell differentiation from the marrow was unaffected by gamma radiation. In conclusion, acute ionizing gamma irradiation at 100 cGy (but not at 1 cGy or 10 cGy) exacerbated microarchitectural changes normally found during progressive, postpubertal aging prior to the onset of age-related osteoporosis.« less

  12. Genetic Background Modulates lncRNA-Coordinated Tissue Response to Low Dose Ionizing Radiation

    DOE PAGESBeta

    Tang, Jonathan; Huang, Yurong; Nguyen, David H.; Costes, Sylvain V.; Snijders, Antoine M.; Mao, Jian-Hua

    2015-01-01

    Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed aftermore » LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.« less

  13. Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation

    PubMed Central

    Lee, Hae-June; Kim, Joong-Sun; Song, Myoung-Sub; Seo, Heung-Sik; Yang, Miyoung; Kim, Jong Choon; Jo, Sung-Kee; Shin, Taekyun

    2010-01-01

    This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis. PMID:20195069

  14. Identification and Characterization of Soluble Factors Involved in Delayed Effects of Low Dose Radiation. Final report

    SciTech Connect

    Baulch, Janet

    2013-09-11

    This is a 'glue grant' that was part of a DOE Low Dose project entitled 'Identification and Characterization of Soluble Factors Involved in Delayed Effects of Low Dose Radiation'. This collaborative program has involved Drs. David L. Springer from Pacific Northwest National Laboratory (PNNL), John H. Miller from Washington State University, Tri-cities (WSU) and William F. Morgan then from the University of Maryland, Baltimore (UMB). In July 2008, Dr. Morgan moved to PNNL and Dr. Janet E. Baulch became PI for this project at University of Maryland. In November of 2008, a one year extension with no new funds was requested to complete the proteomic analyses. The project stemmed from studies in the Morgan laboratory demonstrating that genomically unstable cells secret a soluble factor or factors into the culture medium, that cause cytogenetic aberrations and apoptosis in normal parental GM10115 cells. The purpose of this project was to identify the death inducing effect (DIE) factor or factors, estimate their relative abundance, identify the cell signaling pathways involved and finally recapitulate DIE in normal cells by exogenous manipulation of putative DIE factors in culture medium. As reported in detail in the previous progress report, analysis of culture medium from the parental cell line, and stable and unstable clones demonstrated inconsistent proteomic profiles as relate to candidate DIE factors. While the proposed proteomic analyses did not provide information that would allow DIE factors to be identified, the analyses provided another important set of observations. Proteomic analysis suggested that proteins associated with the cellular response to oxidative stress and mitochondrial function were elevated in the medium from unstable clones in a manner consistent with mitochondrial dysfunction. These findings correlate with previous studies of these clones that demonstrated functional differences between the mitochondria of stable and unstable clones. These

  15. Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

    SciTech Connect

    Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael; Leamon, Christopher P.; Low, Philip S.

    2008-06-01

    Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm{sup 3} before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm{sup 3} subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon {alpha}) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm{sup 3}. More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

  16. Pulmonary Injury after Combined Exposures to Low-Dose Low-LET Radiation and Fungal Spores

    PubMed Central

    Marples, B.; Downing, L.; Sawarynski, K. E.; Finkelstein, J. N.; Williams, J. P.; Martinez, A. A.; Wilson, G. D.; Sims, M. D.

    2013-01-01

    Exposure to infectious microbes is a likely confounder after a nuclear terrorism event. In combination with radiation, morbidity and mortality from an infection may increase significantly. Pulmonary damage after low-dose low-LET irradiation is characterized by an initial diffuse alveolar inflammation. By contrast, inhaled fungal spores produce localized damage around pulmonary bronchioles. In the present study, we assessed lung injury in C57BL/6 mice after combined exposures to whole-body X radiation and inhaled fungal spores. Either animals were exposed to Aspergillus spores and immediately irradiated with 2 Gy, or the inoculation and irradiation were separated by 8 weeks. Pulmonary injury was assessed at 24 and 48 h and 1, 2, 4, 8, and 24 weeks later using standard H&E-stained sections and compared with sham-treated age-matched controls. Immunohistochemistry for invasive inflammatory cells (macrophages, neutrophils and B and T lymphocytes) was performed. A semi-quantitative assessment of pulmonary injury was made using three distinct parameters: local infiltration of inflammatory cells, diffuse inflammation, and thickening and distortion of alveolar architecture. Radiation-induced changes in lung architecture were most evident during the first 2 weeks postexposure. Fungal changes were seen over the first 4 weeks. Simultaneous combined exposures significantly increased the duration of acute pulmonary damage up to 24 weeks (P < 0.01). In contrast, administration of the fungus 8 weeks after irradiation did not produce enhanced levels of acute pulmonary damage. These data imply that the inhalation of fungal spores at the time of a radiation exposure alters the susceptibility of the lungs to radiation-induced injury. PMID:21275606

  17. Extracting Gene Networks for Low-Dose Radiation Using Graph Theoretical Algorithms

    PubMed Central

    Voy, Brynn H; Scharff, Jon A; Perkins, Andy D; Saxton, Arnold M; Borate, Bhavesh; Chesler, Elissa J; Branstetter, Lisa K; Langston, Michael A

    2006-01-01

    Genes with common functions often exhibit correlated expression levels, which can be used to identify sets of interacting genes from microarray data. Microarrays typically measure expression across genomic space, creating a massive matrix of co-expression that must be mined to extract only the most relevant gene interactions. We describe a graph theoretical approach to extracting co-expressed sets of genes, based on the computation of cliques. Unlike the results of traditional clustering algorithms, cliques are not disjoint and allow genes to be assigned to multiple sets of interacting partners, consistent with biological reality. A graph is created by thresholding the correlation matrix to include only the correlations most likely to signify functional relationships. Cliques computed from the graph correspond to sets of genes for which significant edges are present between all members of the set, representing potential members of common or interacting pathways. Clique membership can be used to infer function about poorly annotated genes, based on the known functions of better-annotated genes with which they share clique membership (i.e., “guilt-by-association”). We illustrate our method by applying it to microarray data collected from the spleens of mice exposed to low-dose ionizing radiation. Differential analysis is used to identify sets of genes whose interactions are impacted by radiation exposure. The correlation graph is also queried independently of clique to extract edges that are impacted by radiation. We present several examples of multiple gene interactions that are altered by radiation exposure and thus represent potential molecular pathways that mediate the radiation response. PMID:16854212

  18. Low doses of gamma radiation in the management of postharvest Lasiodiplodia theobromae in mangos

    PubMed Central

    Santos, Alice Maria Gonçalves; Lins, Severina Rodrigues Oliveira; da Silva, Josenilda Maria; de Oliveira, Sônia Maria Alves

    2015-01-01

    The postharvest life of mango is limited by the development of pathogens, especially fungi that cause rot, among which stands out the Lasiodiplodia theobromae. Several control methods have been employed to minimize the damages caused by this fungus, chemical control can leave residues to man and nature; physical control by the use of gamma radiation in combination with modified atmosphere and cold storage. The use of gamma radiation helps to reduce the severity of the pathogen assist in the ripening process of fruits, even at low doses (0.25, 0.35 and 0.45 kGy) chemical properties such as pH, soluble solids, acid ascorbic, titratable acidity and also the quality parameters of the pulp showed no damage that are ideal for trade and consumption of mangoes. This treatment can be extended for use in the management of diseases such as natural infections for penducular rot complex that has as one of L. theobroma pathogens involved. PMID:26413068

  19. Potential Treatment of Inflammatory and Proliferative Diseases by Ultra-Low Doses of Ionizing Radiations

    PubMed Central

    Sanders, Charles L.

    2012-01-01

    Ultra-low doses and dose- rates of ionizing radiation are effective in preventing disease which suggests that they also may be effective in treating disease. Limited experimental and anecdotal evidence indicates that low radiation doses from radon in mines and spas, thorium-bearing monazite sands and enhanced radioactive uranium ore obtained from a natural geological reactor may be useful in treating many inflammatory conditions and proliferative disorders, including cancer. Optimal therapeutic applications were identified via a literature survey as dose-rates ranging from 7 to 11μGy/hr or 28 to 44 times world average background rates. Rocks from an abandoned uranium mine in Utah were considered for therapeutic application and were examined by γ-ray and laser-induced breakdown fluorescence spectroscopy. The rocks showed the presence of transuranics and fission products with a γ-ray energy profile similar to aged spent uranium nuclear fuel (93% dose due to β particles and 7% due to γ rays). Mud packs of pulverized uranium ore rock dust in sealed plastic bags delivering bag surface β,γ dose-rates of 10–450 μGy/h were used with apparent success to treat several inflammatory and proliferative conditions in humans. PMID:23304108

  20. Low doses of gamma radiation in the management of postharvest Lasiodiplodia theobromae in mangos.

    PubMed

    Santos, Alice Maria Gonçalves; Lins, Severina Rodrigues Oliveira; Silva, Josenilda Maria da; Oliveira, Sônia Maria Alves de

    2015-01-01

    The postharvest life of mango is limited by the development of pathogens, especially fungi that cause rot, among which stands out the Lasiodiplodia theobromae. Several control methods have been employed to minimize the damages caused by this fungus, chemical control can leave residues to man and nature; physical control by the use of gamma radiation in combination with modified atmosphere and cold storage. The use of gamma radiation helps to reduce the severity of the pathogen assist in the ripening process of fruits, even at low doses (0.25, 0.35 and 0.45 kGy) chemical properties such as pH, soluble solids, acid ascorbic, titratable acidity and also the quality parameters of the pulp showed no damage that are ideal for trade and consumption of mangoes. This treatment can be extended for use in the management of diseases such as natural infections for penducular rot complex that has as one of L. theobroma pathogens involved. PMID:26413068

  1. Simulation of TGF-Beta Activation by Low-Dose HZE Radiation in a Cell Culture

    NASA Technical Reports Server (NTRS)

    Plante, Ianik; Cucinotta, Francis A.

    2009-01-01

    High charge (Z) and energy (E) (HZE) nuclei comprised in the galactic cosmic rays are main contributors to space radiation risk. They induce many lesions in living matter such as non-specific oxidative damage and the double-strand breaks (DSBs), which are considered key precursors of early and late effects of radiation. There is increasing evidence that cells respond collectively rather than individually to radiation, suggesting the importance of cell signaling1. The transforming growth factor (TGF ) is a signaling peptide that is expressed in nearly all cell type and regulates a large array of cellular processes2. TGF have been shown to mediate cellular response to DNA damage3 and to induce apoptosis in non-irradiated cells cocultured with irradiated cells4. TFG molecules are secreted by cells in an inactive complex known as the latency-associated peptide (LAP). TGF is released from the LAP by a conformational change triggered by proteases, thrombospondin-1, integrins, acidic conditions and .OH radical5. TGF then binds to cells receptors and activates a cascade of events mediated by Smad proteins6, which might interfere with the repair of DNA. Meanwhile, increasingly sophisticated Brownian Dynamics (BD) algorithms have appeared recently in the literature7 and can be applied to study the interaction of molecules with receptors. These BD computer models have contributed to the elucidation of signal transduction, ligand accumulation and autocrine loops in the epidermal growth factor (EGF) and its receptor (EFGR) system8. To investigate the possible roles of TGF in an irradiated cell culture, our Monte-Carlo simulation codes of the radiation track structure9 will be used to calculate the activation of TFG triggered by .OH produced by low doses of HZE ions. The TGF molecules will then be followed by a BD algorithm in a medium representative of a cell culture to estimate the number of activated receptors.

  2. Chloroquine improves survival and hematopoietic recovery following lethal low dose- rate radiation

    PubMed Central

    Lim, Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang, Yonggang; Yu, Hsiang-Hsuan M; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-01-01

    Purpose We have previously shown that the anti-malarial agent chloroquine can abrogate the lethal cellular effects of low dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials C57BL/6 mice were irradiated with total of 12.8 Gy delivered at 9.4 cGy/hr. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 μg per 17 g of body weight, 24 hrs and 4 hrs before irradiation. Bone marrow cells isolated from tibia, fibula and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retro orbital injection. Chimerism was assessed by flow cytometry. In vitro methyl cellulose colony forming assay of whole bone marrow cells as well as FACS analysis of lineage depleted cells was used to assess the effect of chloroquine on progenitor cells. Results Mice pretreated with chloroquine prior to radiation exhibited a significantly higher survival rate compared to mice treated with radiation alone (80 vs.31 percent, p=0.0026). Chloroquine administration prior to radiation did not impact the survival of ATM null mice (p=0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after the transplantation (4.2 percent vs. 0.4 percent, p=0.015). Conclusion Chloroquine administration prior to radiation had a significant effect on the survival of normal but not ATM null mice strongly suggesting that the in vivo effect like the in vitro effect is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection against the

  3. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    SciTech Connect

    Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M.; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-11-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  4. Low dose alpha interferon therapy can be effective in chronic active hepatitis C. Results of a multicentre, randomised trial.

    PubMed Central

    Sánchez-Tapias, J M; Forns, X; Ampurdanés, S; Titó, L; Planas, R; Viver, J M; Acero, D; Torres, M; Mas, P; Morillas, R; Forné, M; Espinós, J; Llovet, J M; Costa, J; Olmedo, E; López-Labrador, F X; Jiménez de Anta, M T; Rodés, J

    1996-01-01

    BACKGROUND--There is some controversy concerning the efficacy of low dose alpha interferon therapy in chronic hepatitis C. AIMS--To evaluate the effectiveness of treatment with low doses of alpha interferon in chronic hepatitis C. PATIENTS--One hundred and forty one patients with anti-HCV positive chronic active hepatitis C from six hospitals were enrolled in the study. METHODS--Patients were randomised to treatment with 5 MU (group A) or 1.5 MU (group B) injections. The dose was reduced in responders from group A or increased in non-responders from group B to maintain treatment with the minimal effective dose. Patients were treated for 48 weeks and followed up for 24 additional weeks with no treatment. Normalisation of alanine aminotransferase (ALT) was used to evaluate response. RESULTS--A sustained response was seen in eight patients from group A (12%) and in 15 (21%) from group B. This difference was not statistically significant. Increasing the dose of interferon led to sustained response in only five of 58 patients (9%) from group B who did not respond to 1.5 MU injections. In contrast, 15 of 21 patients (71%) in whom ALT remained normal with 1.5 MU injections developed a sustained response. By multivariate analysis sustained response seemed associated with young age and was more frequent in patients with genotype 3 HCV infection. Sustained response was preceded by a rapid normalisation of ALT and was inversely related to the amount of alpha interferon necessary to maintain ALT at low values during treatment. CONCLUSIONS--Some patients with chronic hepatitis C are very sensitive to alpha interferon and can be successfully treated with low doses. Treatment with higher doses may be effective in a minority of patients who do not respond to low doses. PMID:8707096

  5. Individual Human Cell Responses to Low Doses of Chemicals and Radiation Studied by Synchrotron Infrared Spectromicroscopy

    NASA Astrophysics Data System (ADS)

    Martin, Michael C.; Holman, Hoi-Ying N.; Blakely, Eleanor A.; Goth-Goldstein, Regine; McKinney, Wayne R.

    2000-03-01

    Vibrational spectroscopy, when combined with synchrotron radiation-based (SR) microscopy, is a powerful new analytical tool with high spatial resolution for detecting biochemical changes in individual living cells. In contrast to other microscopy methods that require fixing, drying, staining or labeling, SR FTIR microscopy probes intact living cells providing a composite view of all of the molecular responses and the ability to monitor the responses over time in the same cell. Observed spectral changes include all types of lesions induced in that cell as well as cellular responses to external and internal stresses. These spectral changes combined with other analytical tools may provide a fundamental understanding of the key molecular mechanisms induced in response to stresses created by low-doses of radiation and chemicals. In this study we used high spatial-resolution SR FTIR vibrational spectromicroscopy at ALS Beamline 1.4.3 as a sensitive analytical tool to detect chemical- and radiation-induced changes in individual human cells. Our preliminary spectral measurements indicate that this technique is sensitive enough to detect changes in nucleic acids and proteins of cells treated with environmentally relevant concentrations of oxidative stresses: bleomycin, hydrogen peroxide, and X-rays. We observe spectral changes that are unique to each exogenous stressor. This technique has the potential to distinguish changes from exogenous or endogenous oxidative processes. Future development of this technique will allow rapid monitoring of cellular processes such as drug metabolism, early detection of disease, bio-compatibility of implant materials, cellular repair mechanisms, self assembly of cellular apparatus, cell differentiation and fetal development.

  6. James V. Neel and Yuri E. Dubrova: Cold War debates and the genetic effects of low-dose radiation.

    PubMed

    Goldstein, Donna M; Stawkowski, Magdalena E

    2015-01-01

    This article traces disagreements about the genetic effects of low-dose radiation exposure as waged by James Neel (1915-2000), a central figure in radiation studies of Japanese populations after World War II, and Yuri Dubrova (1955-), who analyzed the 1986 Chernobyl nuclear power plant accident. In a 1996 article in Nature, Dubrova reported a statistically significant increase in the minisatellite (junk) DNA mutation rate in the children of parents who received a high dose of radiation from the Chernobyl accident, contradicting studies that found no significant inherited genetic effects among offspring of Japanese A-bomb survivors. Neel's subsequent defense of his large-scale longitudinal studies of the genetic effects of ionizing radiation consolidated current scientific understandings of low-dose ionizing radiation. The article seeks to explain how the Hiroshima/Nagasaki data remain hegemonic in radiation studies, contextualizing the debate with attention to the perceived inferiority of Soviet genetic science during the Cold War.

  7. James V. Neel and Yuri E. Dubrova: Cold War debates and the genetic effects of low-dose radiation.

    PubMed

    Goldstein, Donna M; Stawkowski, Magdalena E

    2015-01-01

    This article traces disagreements about the genetic effects of low-dose radiation exposure as waged by James Neel (1915-2000), a central figure in radiation studies of Japanese populations after World War II, and Yuri Dubrova (1955-), who analyzed the 1986 Chernobyl nuclear power plant accident. In a 1996 article in Nature, Dubrova reported a statistically significant increase in the minisatellite (junk) DNA mutation rate in the children of parents who received a high dose of radiation from the Chernobyl accident, contradicting studies that found no significant inherited genetic effects among offspring of Japanese A-bomb survivors. Neel's subsequent defense of his large-scale longitudinal studies of the genetic effects of ionizing radiation consolidated current scientific understandings of low-dose ionizing radiation. The article seeks to explain how the Hiroshima/Nagasaki data remain hegemonic in radiation studies, contextualizing the debate with attention to the perceived inferiority of Soviet genetic science during the Cold War. PMID:25001362

  8. Low dose radiation interactions with the transformation growth factor (TFG)-beta pathway

    NASA Astrophysics Data System (ADS)

    Maslowski, Amy Jesse

    A major limiting factor for long-term, deep-space missions is the radiation dose to astronauts. Because the dose to the astronauts is a mixed field of low- and high-LET radiation, there is a need to understand the effects of both radiation types on whole tissue; however, there are limited published data on the effects of high-LET (linear-energy-transfer) radiation on tissue. Thus, we designed a perfusion chamber system for rat trachea in order to mimic in vivo respiratory tissue. We successfully maintained the perfused tracheal tissue ex vivo in a healthy and viable condition for up to three days. In addition, this project studied the effects of high-LET Fe particles on the overall transformation growth factor (TGF)-beta response after TGF-beta inactivation and compared the results to the TGF-beta response post x-ray irradiation. It was found that a TGF-beta response could be measured in the perfused tracheal tissue, for x-ray and Fe particle irradiations, despite the high autofluorescent background intrinsic to tissue. However, after comparing the TGF-beta response of x-ray irradiation to High-Z-High-energy (HZE) irradiation, there was not a significant difference in radiation types. The TGF-beta response in x-ray and HZE irradiated perfusion chambers was also measured over time post irradiation. It was found that for 6 hour and 8 hour post irradiation, the TGF-beta response was higher for lower doses of radiation than for higher doses. This is in contrast to the 0 hour fixation which found the TGF-beta response to increase with increased dose. The inverse relationship found for 6 hour and 8 hour fixation times may indicate a threshold response for TGF-beta response; i.e., for low doses, a threshold of dose must be reached for an immediate TGF-beta response, otherwise the tissue responds more slowly to the irradiation damage. This result was unexpected and will require further investigation to determine if the threshold can be determined for the 250 kVp x-rays and

  9. Mutations of the human interferon alpha-2b (hIFN-α2b) gene in occupationally protracted low dose radiation exposed personnel.

    PubMed

    Shahid, Saman; Mahmood, Nasir; Chaudhry, Muhammad Nawaz; Sheikh, Shaharyar; Ahmad, Nauman

    2015-05-01

    Ionizing radiations impact human tissues by affecting the DNA bases which constitute genes. Human interferon alpha 2b gene synthesizes a protein which is an important anticancerous, immunomodulatory, anti-proliferative and antiviral protein. This study was aimed to identify interferon alpha-2b mutations as a consequence of the use of occupational chronic low dose radiation by hospital radiation exposed workers. A molecular analysis was done in which DNAs were extracted from blood samples from radiology, radiotherapy and nuclear medicine workers. The gene was amplified through polymerase chain reaction and further genetic data from sequencing results analyzed by bioinformatics tools in order to determine as to how mutations in interferon alpha 2b sequences will lead to changes in human interferon alpha-2b protein. A total of 41% gene mutations was detected among all radiation exposed workers in which higher percentage (5.4%) of base insertion mutations and 14% frameshift mutations were found in radiology workers. The chronic use of low dose of radiations by occupational workers has a significant correlation with mutational effects on interferon alpha 2b gene, further evident by depressed interferon alpha levels in serum. This can lead to depressed immunity in radiation exposed workers. Hematological profiling of this group also showed hyperimmune response in the form of lymphocytosis.

  10. Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation.

    PubMed

    Kim, Rae-Kwon; Kim, Min-Jung; Seong, Ki Moon; Kaushik, Neha; Suh, Yongjoon; Yoo, Ki-Chun; Cui, Yan-Hong; Jin, Young Woo; Nam, Seon Young; Lee, Su-Jae

    2015-01-01

    Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen. PMID:26515758

  11. Effects of low dose particle radiation to mice and its premature neurons in culture

    NASA Astrophysics Data System (ADS)

    Nojima, K.; Nagaoka, S.

    To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions and X ray at fifth days of the culture. The applied dose varied from 0.05Gy up to 2.0Gy. The subsequent biological effects were evaluated by an induction of apoptosis focusing on the dependencies of (1) the animal strains with different radiation sensitivities, and (2) LET with different nucleon types. Of the three mouse strains, SCID , B6 and C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to both X ray and carbon ion (290MeV/n) as evaluated by 10 % apoptotic criteria.- However, the sensitivity differences among the strains were much smaller in case of carbon ion comparing to that of X-ray. Regarding the LET dependency, the sensitivity was compared with using C3H and B6 cells between the carbon (13 keV/μm) and neon (70 keV/μm ) ions. Carbon (290 MeV/n) did not show a detectable LET dependency as judged by the criteria whereas the neon (400 MeV/n) showed 1.4 fold difference for both C3H and B6 cells. Although a LET dependency was examined by using the most sensitive SCID cells, no significant difference was detected. In this repot, a preliminary result w ill be presented on learning function of adult mice after localized heavy particle irradiation directly to brain.

  12. Mechanisms underlying the adaptive response against spontaneous neoplastic transformation induced by low doses of low LET radiation - Final Technical Report

    SciTech Connect

    John Leslie Redpath

    2007-01-17

    The objective of the research was to examine mechanisms underlying the suppressive effects of low doses (<10 cGy) of low-LET radiation on the endpoint of neoplastic transformation in vitro. The findings indicated a role for upregulation of DNA repair but not of antioxidants.

  13. A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

    SciTech Connect

    Balmain, Allan; Song, Ihn Young

    2013-05-15

    The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

  14. Radiation quality and the shape of dose-effect curves at low doses of ionizing radiation for eukaryotic cells.

    PubMed

    Petin, V G; Kapultcevich, Yu G

    2014-06-01

    To explain different yeast and mammalian cell response to low and high linear energy transfer (LET) radiation in low dose region, the dependence of fine target structure on the stage of cell growth was supposed. Theoretical consideration based on this suggestion was carried out. Results of calculations are qualitatively in agreement with experimental data under assuming that hit-event for both mammalian and yeast cells is a group of ionizations produced by the same ionizing particle. In the dependence of cell cycle phase, sensitive sites (presumable the vulnerable sections of chromosomes) can be located either in periphery of cell nucleus forming a thin layer inside the nucleus or distributed evenly over the whole nucleus. Such rearrangement of the target results in the alteration of the dependence of both survival curve shape and the relative biological effectiveness values on radiation quality.

  15. The effect of low dose ionizing radiation on homeostasis and functional integrity in an organotypic human skin model

    SciTech Connect

    von Neubeck, Claere; Geniza, Matthew; Kauer, Paula M.; Robinson, Joseph E.; Chrisler, William B.; Sowa, Marianne B.

    2015-05-01

    Outside the protection of earth’s atmosphere, astronauts are exposed to low doses of high linear energy transfer (LET) radiation. Future NASA plans for deep space missions or a permanent settlement on the moon are limited by the health risks associated with space radiation exposures. There is a paucity of direct epidemiological data for low dose exposures to space radiation-relevant high LET ions. Health risk models are used to estimate the risk for such exposures, though these models are based on high dose experiments. There is increasing evidence, however, that low and high dose exposures result in different signaling events at the molecular level, and may involve different response mechanisms. Further, despite their low abundance, high LET particles have been identified as the major contributor to health risk during manned space flight. The human skin is exposed in every external radiation scenario, making it an ideal epithelial tissue model in which to study radiation induced effects. Here, we exposed an in vitro three dimensional (3-D) human organotypic skin tissue model to low doses of high LET oxygen (O), silicon (Si) and iron (Fe) ions. We measured proliferation and differentiation profiles in the skin tissue and examined the integrity of the skin’s barrier function. We discuss the role of secondary particles in changing the proportion of cells receiving a radiation dose, emphasizing the possible impact on radiation-induced health issues in astronauts.

  16. Protecting effects specifically from low doses of ionizing radiation to mammalian cells challenge the concept of linearity

    SciTech Connect

    Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.; Altman, K.I.

    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 changes in intracellular signaling that induce mechanisms of DNA damage control different from those operating 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. The aim of this paper is to demonstrate that by use of microdosimetric concepts, the energy deposited in cell mass can be related to the occurrence of cellular responses, both damaging and defensive.

  17. Array-CGH analyses of murine malignant lymphomas: genomic clues to understanding the effects of chronic exposure to low-dose-rate gamma rays on lymphomagenesis.

    PubMed

    Takabatake, Takashi; Fujikawa, Katsuyoshi; Tanaka, Satoshi; Hirouchi, Tokuhisa; Nakamura, Masako; Nakamura, Shingo; Braga-Tanaka, Ignacia; Ichinohe, Kazuaki; Saitou, Mikio; Kakinuma, Shizuko; Nishimura, Mayumi; Shimada, Yoshiya; Oghiso, Yoichi; Tanaka, Kimio

    2006-07-01

    We previously reported that mice chronically irradiated with low-dose-rate gamma rays had significantly shorter mean life spans than nonirradiated controls. This life shortening appeared to be due primarily to earlier death due to malignant lymphomas in the irradiated groups (Tanaka et al., Radiat. Res. 160, 376-379, 2003). To elucidate the molecular pathogenesis of murine lymphomas after low-dose-rate irradiation, chromosomal aberrations in 82 malignant lymphomas from mice irradiated at a dose rate of 21 mGy/day and from nonirradiated mice were compared precisely by microarray-based comparative genomic hybridization (array-CGH) analysis. The array carried 667 BAC clones densely selected for the genomic regions not only of lymphoma-related loci but also of surface antigen receptors, enabling immunogenotyping. Frequent detection of the apparent loss of the Igh region on chromosome 12 suggested that most lymphomas in both groups were of B-cell origin. Array-CGH profiles showed a frequent gain of whole chromosome 15 in lymphomas predominantly from the irradiated group. The profiles also demonstrated copy-number imbalances of partial chromosomal regions. Partial gains on chromosomes 12, 14 and X were found in tumors from nonirradiated mice, whereas losses on chromosomes 4 and 14 were significantly associated with the irradiated group. These findings suggest that lymphomagenesis under the effects of continuous low-dose-rate irradiation is accelerated by a mechanism different from spontaneous lymphomagenesis that is characterized by the unique spectrum of chromosomal aberrations. PMID:16808621

  18. Seizures associated with low-dose tramadol for chronic pain treatment

    PubMed Central

    Beyaz, Serbülent Gökhan; Sonbahar, Tuğba; Bayar, Fikret; Erdem, Ali Fuat

    2016-01-01

    The management of cancer pain still poses a major challenge for clinicians. Tramadol is a centrally acting synthetic opioid analgesic. Its well-known side effects include nausea, vomiting, and dizziness; seizures are a rare side effect. Some reports have found that tramadol triggers seizure activity at high doses, whereas a few preclinical studies have found that this seizure activity is not dose-related. We herein present a case involving a patient with laryngeal cancer who developed seizures while on low-dose oral tramadol. PMID:27212778

  19. Dosimetry for quantitative analysis of low dose ionizing radiation effects on humans in radiation therapy patients

    SciTech Connect

    Lehmann, J; Stern, R L; Daly, T P; Schwieter, C W; Jones, G E; Arnold, M L; Hartmann-Siantar, C L; Goldberg, Z

    2004-04-20

    We have successfully developed a practical approach to predicting the location of skin surface dose at potential biopsy sites that receive 1 cGy and 10 cGy, respectively, in support of in vivo biologic dosimetry in humans. This represents a significant technical challenge as the sites lie on the patient surface out side the radiation fields. The PEREGRINE Monte Carlo simulation system was used to model radiation dose delivery and TLDs were used for validation on a phantom and confirmation during patient treatment. In the developmental studies the Monte Carlo simulations consistently underestimated the dose at the biopsy site by approximately 15% for a realistic treatment configuration, most likely due to lack of detail in the simulation of the linear accelerator outside the main beam line. Using a single, thickness-independent correction factor for the clinical calculations, the average of 36 measurements for the predicted 1 cGy point was 0.985 cGy (standard deviation: 0.110 cGy) despite patient breathing motion and other real world challenges. Since the 10 cGy point is situated in the region of high dose gradient at the edge of the field, patient motion had a greater effect and the six measured points averaged 5.90 cGy (standard deviation: 1.01 cGy), a difference that is equivalent to approximately a 6 mm shift on the patient's surface.

  20. Application of Low Dose Radiation Adaptive Response to Control Aging-Related Disease

    SciTech Connect

    Doss, Mohan

    2013-11-01

    Oxidative damage has been implicated in the pathogenesis of most aging-related diseases including neurodegenerative diseases. Antioxidant supplementation has been found to be ineffective in reducing such diseases, but increased endogenous production of antioxidants from the adaptive response due to physical and cognitive exercises (which increase oxidative metabolism and oxidative stress) has been effective in reducing some of the diseases. Low dose radiation (LDR), which increases oxidative stress and results in adaptive response of increased antioxidants, may provide an alternative method of controlling the aging-related diseases. We have studied the effect of LDR on the induction of adaptive response in rat brains and the effectiveness of the LDR in reducing the oxidative damage caused by subsequent high dose radiation. We have also investigated the effect of LDR on apomorphine-induced rotations in the 6-hydroxydopamine (6-OHDA) unilaterally-lesioned rat model of Parkinson?s disease (PD). LDR was observed to initiate an adaptive response in the brain, and reduce the oxidative damage from subsequent high dose radiation exposure, confirming the effectiveness of LDR adaptive response in reducing the oxidative damage from the free radicals due to high dose radiation. LDR resulted in a slight improvement in Tyrosine hydroxylase expression on the lesioned side of substantia nigra (indicative of its protective effect on the dopaminergic neurons), and reduced the behavioral symptoms in the 6-OHDA rat model of PD. Translation of this concept to humans, if found to be applicable, may be a possible approach for controlling the progression of PD and other neurodegenerative diseases. Since any translation of the concept to humans would be hindered by the currently prevalent carcinogenic concerns regarding LDR based on the linear no-threshold (LNT) model, we have also studied the justifications for the use of the LNT model. One of the shortcomings of the LNT model is that it

  1. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    NASA Technical Reports Server (NTRS)

    Hada, M.; George, Kerry; Cucinotta, Francis A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

  2. Evidence for Radiation Hormesis After In Vitro Exposure of Human Lymphocytes to Low Doses of Ionizing Radiation§

    PubMed Central

    Rithidech, Kanokporn Noy; Scott, Bobby R.

    2008-01-01

    Previous research has demonstrated that adding a very small gamma-ray dose to a small alpha radiation dose can completely suppress lung cancer induction by alpha radiation (a gamma-ray hormetic effect). Here we investigated the possibility of gamma-ray hormesis during low-dose neutron irradiation, since a small contribution to the total radiation dose from neutrons involves gamma rays. Using binucleated cells with micronuclei (micronucleated cells) among in vitro monoenergetic-neutron-irradiated human lymphocytes as a measure of residual damage, we investigated the influence of the small gamma-ray contribution to the dose on suppressing residual damage. We used residual damage data from previous experiments that involved neutrons with five different energies (0.22-, 0.44-, 1.5-, 5.9-, and 13.7-million electron volts [MeV]). Corresponding gamma-ray contributions to the dose were approximately 1%, 1%, 2%, 6%, and 6%, respectively. Total absorbed radiation doses were 0, 10, 50, and 100 mGy for each neutron source. We demonstrate for the first time a protective effect (reduced residual damage) of the small gamma-ray contribution to the neutron dose. Using similar data for exposure to gamma rays only, we also demonstrate a protective effect of 10 mGy (but not 50 or 100 mGy) related to reducing the frequency of micronucleated cells to below the spontaneous level. PMID:18846261

  3. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    SciTech Connect

    Chung, Eugene; Corbett, James R.; Moran, Jean M.; Griffith, Kent A.; Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L.; Ficaro, Edward C.; Pierce, Lori J.

    2013-03-15

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

  4. The bovine tuberculosis burden in cattle herds in zones with low dose radiation pollution in the Ukraine

    SciTech Connect

    Weller, Richard E.; Skrypnyk, Artem; Zavgorodniy, Andriy; Stegniy, Borys; Gerilovych, Anton; Kutsan, Oleksandr; Pozmogova, Svitlana; Sapko, Svitlana

    2009-02-01

    The authors describe a study of the tuberculosis (TB) incidence in cattle exposed to low doses of radiation resulting from the Chernobyl (pronounced ‘Chornobyl’ in Ukrainian) nuclear plant catastrophe in 1986. The purpose of the study was to determine if ionising radiation influences the number of outbreaks of bovine TB and their severity on farms in the Kyiv, Cherkasy and Chernigiv regions of the Ukraine. These farms are all located within a 200 km radius of Chernobyl and have had low-dose radiation pollution. Pathological and blood samples were taken from cattle in those regions that had positive TB skin tests. Mycobacterium spp. were isolated, differentiated by PCR, analysed and tested in guinea pigs and rabbits. Species differentiation showed a significant percentage of atypical mycobacteria, which resulted in the allergic reactions to tuberculin antigen in the skin test. Mixed infection of M. bovis and M. avium subsp. hominissuis was found in three cases. The results concluded that low-dose radiation plays a major role in the occurrence of bovine TB in regions affected by the Chernobyl nuclear disaster.

  5. Low-Dose Gamma Radiation Does Not Induce an Adaptive Response for Micronucleus Induction in Mouse Splenocytes.

    PubMed

    Bannister, L A; Serran, M L; Mantha, R R

    2015-11-01

    Low-dose ionizing radiation is known to induce radioadaptive responses in cells in vitro as well as in mice in vivo. Low-dose radiation decreases the incidence and increases latency for spontaneous and radiation-induced tumors in mice, potentially as a result of enhanced cellular DNA repair efficiency or a reduction in genomic instability. In this study, the cytokinesis-block micronucleus (CBMN) assay was used to examine dose response and potential radioadaptive response for cytogenetic damage and cell survival in C57BL/6 and BALB/c spleen cells exposed in vitro or in vivo to low-dose 60Co gamma radiation. The effects of genetic background, radiation dose and dose rate, sampling time and cell cycle were investigated with respect to dose response and radioadaptive response. In C57BL/6 mice, a linear-quadratic dose-response relationship for the induction of micronuclei (MN) was observed for doses between 100 mGy and 2 Gy. BALB/c mice exhibited increased radiosensitivity for MN induction compared to C57BL/6 mice. A 20 mGy dose had no effect on MN frequencies in splenocytes of either mouse strain, however, increased spleen weight and a reduced number of dead cells were noted in the C57BL/6 strain only. Multiple experimental parameters were investigated in radioadaptive response studies, including dose and dose rate of the priming dose (20 mGy at 0.5 mGy/min and 100 mGy at 10 mGy/min), time interval (4 and 24 h) between priming and challenge doses, cell cycle stage (resting or proliferating) at exposure and kinetics after the challenge dose. Radioadaptive responses were not observed for MN induction for either mouse strain under any of the experimental conditions investigated. In contrast, a synergistic response for radiation-induced micronuclei in C57BL/6 spleen was detected after in vivo 20 mGy irradiation. This increase in the percentage of cells with cytogenetic damage was associated with a reduction in the number of nonviable spleen cells, suggesting that low-dose

  6. Effects of low doses and low dose rates of external ionizing radiation: Cancer mortality among nuclear industry workers in three countries

    SciTech Connect

    Cardis, E.; Kato, I.; Lave, C.; Gilbert, E.S.; Fix., J.; Carpenter, L.; Howe, D.; Armstrong, B.K.; Bereal, V.

    1995-05-01

    Studies of the mortality among nuclear industry workforces have been carried out, and nationally combined analyses performed, in the U.S., the UK and Canada. This paper presents the results of internationally combined analyses of mortality data on 95,673 workers (85.4% men) monitored for external exposure to ionizing radiation and employed for 6 months or longer in the nuclear industry of one of the three countries. These analyses were undertaken to obtain a more precise direct assessment of the carcinogenic effects of protracted low-level exposure to external, predominantly {gamma}, radiation. The combination of the data from the various studies increases the power to study associations between radiation dose and mortality from all causes or from all cancers. Mortality from leukemia, excluding chronic lymphocytic leukemia (CLL)-the cause of death most strongly and consistently related to radiation dose in studies of atomic bomb survivors and other populations exposed at high dose rates-was significantly associated with cumulative external radiation dose (one-sided P value = 0.046; 119 deaths). Among the 31 other specific types of cancer studied, a significant association was observed only for multiple myeloma (one-sided P value = 0.037; 44 deaths), and this was attributable primarily to the associations reported previously between this disease and radiation dose in the Hanford (U.S.) and Sellafield (UK) cohorts. The excess relative risk (ERR) estimates for all cancers excluding leukemia, and leukemia excluding CLL, the two main groupings of causes of death for which risk estimates have been derived from studies of atomic bomb survivors, were -0.07 per Sv [90% confidence interval (CI):-0.4,0.3] and 2.18 per Sv (90% CI:0.1,5.7), respectively. These values correspond to a relative risk of 0.99 for all cancers excluding leukemia and 1.22 for leukemia excluding CLL for a cumulative protracted dose of 100 mSv compared to O mSv. 53 refs., 1 fig., 8 tabs.

  7. [Specific long-term cellular changes under effects of low doses of radiation].

    PubMed

    Bychkovskaia, I B; Stepanov, R P; Fedortseva, R F

    2002-01-01

    We examined the peculiar form of a tissue postirradiative reaction characterizing by massive, dose-independent transition of cell populations to the steady state modification with the essential raise of cell damage and cell loss probability as compared with the probability level of the same alterations in controls. We described some other signs of such type of cellular transformation. It was found that the indicated cellular condition occurred both in active and slowly proliferating tissues. The reaction occurred at relatively low doses of irradiation. Some nonmutagenic factors also may evoke such effects. Our experimental data allow us to suppose the epigenetic mechanizms taking part in the induction and preservation of such alterations. The discovered form of cellular reaction manifestating in different biological objects may be considered as some general biological tendency. The importance of the studied reaction in the pathogenesis of late consequences of low dose irradiation is discussed. PMID:11898627

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

    SciTech Connect

    Bushberg, J; Boreham, D; Ulsh, B

    2014-06-15

    At dose levels of (approximately) 500 mSv or more, increased cancer incidence and mortality have been clearly demonstrated. However, at the low doses of radiation used in medical imaging, the relationship between dose and cancer risk is not well established. As such, assumptions about the shape of the dose-response curve are made. These assumptions, or risk models, are used to estimate potential long term effects. Common models include 1) the linear non-threshold (LNT) model, 2) threshold models with either a linear or curvilinear dose response above the threshold, and 3) a hormetic model, where the risk is initially decreased below background levels before increasing. The choice of model used when making radiation risk or protection calculations and decisions can have significant implications on public policy and health care decisions. However, the ongoing debate about which risk model best describes the dose-response relationship at low doses of radiation makes informed decision making difficult. This symposium will review the two fundamental approaches to determining the risk associated with low doses of ionizing radiation, namely radiation epidemiology and radiation biology. The strengths and limitations of each approach will be reviewed, the results of recent studies presented, and the appropriateness of different risk models for various real world scenarios discussed. Examples of well-designed and poorly-designed studies will be provided to assist medical physicists in 1) critically evaluating publications in the field and 2) communicating accurate information to medical professionals, patients, and members of the general public. Equipped with the best information that radiation epidemiology and radiation biology can currently provide, and an understanding of the limitations of such information, individuals and organizations will be able to make more informed decisions regarding questions such as 1) how much shielding to install at medical facilities, 2) at

  9. A Commentary on: "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008".

    PubMed

    Brooks, Antone L

    2015-04-01

    This commentary provides a very brief overview of the book "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008" ( http://lowdose.energy.gov ). The book summarizes and evaluates the research progress, publications and impact of the U.S. Department of Energy Low Dose Radiation Research Program over its first 10 years. The purpose of this book was to summarize the impact of the program's research on the current thinking and low-dose paradigms associated with the radiation biology field and to help stimulate research on the potential adverse and/or protective health effects of low doses of ionizing radiation. In addition, this book provides a summary of the data generated in the low dose program and a scientific background for anyone interested in conducting future research on the effects of low-dose or low-dose-rate radiation exposure. This book's exhaustive list of publications coupled with discussions of major observations should provide a significant resource for future research in the low-dose and dose-rate region. However, because of space limitations, only a limited number of critical references are mentioned. Finally, this history book provides a list of major advancements that were accomplished by the program in the field of radiation biology, and these bulleted highlights can be found in last part of chapters 4-10.

  10. A Commentary on: "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008".

    PubMed

    Brooks, Antone L

    2015-04-01

    This commentary provides a very brief overview of the book "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008" ( http://lowdose.energy.gov ). The book summarizes and evaluates the research progress, publications and impact of the U.S. Department of Energy Low Dose Radiation Research Program over its first 10 years. The purpose of this book was to summarize the impact of the program's research on the current thinking and low-dose paradigms associated with the radiation biology field and to help stimulate research on the potential adverse and/or protective health effects of low doses of ionizing radiation. In addition, this book provides a summary of the data generated in the low dose program and a scientific background for anyone interested in conducting future research on the effects of low-dose or low-dose-rate radiation exposure. This book's exhaustive list of publications coupled with discussions of major observations should provide a significant resource for future research in the low-dose and dose-rate region. However, because of space limitations, only a limited number of critical references are mentioned. Finally, this history book provides a list of major advancements that were accomplished by the program in the field of radiation biology, and these bulleted highlights can be found in last part of chapters 4-10. PMID:25768839

  11. 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

    SciTech Connect

    Rocke, David M.

    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.

  12. Chronic Low Dose Fructose infusion Does Not Reverse Glucagon-Mediated Decrease in Hepatic Glucose Utilization

    PubMed Central

    Johnson, Paulette M.; Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E; Lacy, D. Brooks; McGuinness, Owen P.

    2013-01-01

    Objective An adaptation to chronic total parenteral nutrition (TPN; 75% of non protein calories as glucose) is the liver becomes a major consumer of glucose with lactate release as a by-product. The liver is able to further increase liver glucose uptake when a small dose of fructose is acutely infused via the portal system. Glucagon, commonly elevated during inflammatory stress, is a potent inhibitor of glucose uptake by the liver during TPN. The aim was to determine if chronic fructose infusion could overcome the glucagon-mediated decrease in hepatic glucose uptake. Material/methods Studies were performed in conscious insulin-treated chronically catheterized pancreatectomized dogs that adapted to TPN for 33 h. They were then assigned to one of 4 groups: TPN (C), TPN + fructose (4.4 μmol·kg−1·min−1, F), TPN+ glucagon (0.2 pmol·kg−1·min−1, GGN), or a TPN + fructose and glucagon (F+GGN) for an additional 63h (33–96h). Insulin, fructose and glucagon were infused into the portal vein. During that period all animals received a fixed insulin infusion 0.4mU· kg−1·min−1 (33–96h) and the glucose infusion rates were adjusted to maintain euglycemia (6.6 mM). Results Chronic fructose infusion was unable to further enhance net hepatic glucose uptake (NHGU; μmol·kg−1·min−1) (31.1±2.8 vs. 36.1±5.0; C vs. F) nor was it able to overcome glucagon-mediated decrease in NHGU (10.0±4.4 vs. 12.2±3.9; GGN vs. F+GGN). Conclusion In summary, chronic fructose infusion cannot augment liver glucose uptake during TPN nor can it overcome the inhibitory effects of glucagon. PMID:20940071

  13. Proteomics analysis of liver tissues from C57BL/6J mice receiving low-dose 137Cs radiation.

    PubMed

    Yi, Lan; Li, Linwei; Yin, Jie; Hu, Nan; Li, Guangyue; Ding, Dexin

    2016-02-01

    Differentially expressed proteins in liver tissues of C57BL/6J mice receiving low-dose (137)Cs radiation were examined by proteomics analysis. Compared with the control group, 80 proteins were differentially expressed in the irradiated group. Among the 40 randomly selected proteins used for peptide mass fingerprinting analysis and bioinformatics, 24 were meaningful. These proteins were related to antioxidant defense, amino acid metabolism, detoxification, anti-tumor development, amino acid transport, anti-peroxidation, and composition of respiratory chain. Western blot analysis showed that catalase (CAT), glycine N-methyltransferase (GNMT), and glutathione S-transferase P1 (GSTP1) were up-regulated in the irradiated group; these results were in agreement with qPCR results. These results show that CAT, GNMT, and GSTP1 may be related to stress response induced by low-dose irradiation in mice liver. The underlying mechanism however requires further investigation. PMID:26429139

  14. Proteomics analysis of liver tissues from C57BL/6J mice receiving low-dose 137Cs radiation.

    PubMed

    Yi, Lan; Li, Linwei; Yin, Jie; Hu, Nan; Li, Guangyue; Ding, Dexin

    2016-02-01

    Differentially expressed proteins in liver tissues of C57BL/6J mice receiving low-dose (137)Cs radiation were examined by proteomics analysis. Compared with the control group, 80 proteins were differentially expressed in the irradiated group. Among the 40 randomly selected proteins used for peptide mass fingerprinting analysis and bioinformatics, 24 were meaningful. These proteins were related to antioxidant defense, amino acid metabolism, detoxification, anti-tumor development, amino acid transport, anti-peroxidation, and composition of respiratory chain. Western blot analysis showed that catalase (CAT), glycine N-methyltransferase (GNMT), and glutathione S-transferase P1 (GSTP1) were up-regulated in the irradiated group; these results were in agreement with qPCR results. These results show that CAT, GNMT, and GSTP1 may be related to stress response induced by low-dose irradiation in mice liver. The underlying mechanism however requires further investigation.

  15. Radiation-induced apoptosis in SCID mice spleen after low dose irradiation

    NASA Astrophysics Data System (ADS)

    Takahashi, A.; Kondo, N.; Inaba, H.; Uotani, K.; Kiyohara, Y.; Ohnishi, K.; Ohnishi, T.

    To assess the radioadaptive response of the whole body system in mice, we examined the temporal effect of low dose priming as an indicator of challenging irradiation-induced apoptosis through a p53 tumor suppressor protein- mediated signal transduction pathway. The p53 protein also plays an important role both in cell cycle control and DNA repair through cellular signal transduction. Using severe combined immunodeficiency mice defective in DNA-dependent protein kinase catalytic subunit, we examined the role of DNA-dependent protein kinase activity in radioadaptation induced by low dose irradiation. Specific pathogen free 5-week-old female severe combined immunodeficiency mice and the parental mice (CB-17 Icr +/ + were irradiated with X-ray at 3.0 C3y at 1, 2, 3 or 4 weeks after the conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after the challenging irradiation. The p53-dependent apoptosis related Bax proteins on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method The apoptosis incidence in the sections was measured by hematoxylin-eosin staining. The frequency of Bax- and apoptosis-positive cells increased up to 12 h after the challenging irradiation in the spleen of both mice. However, these cells were not observed after a low dose irradiation at 0.15-0.60 Gy When pre-irradiation at 0.45 Gy 2 weeks before the challenging irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by challenging irradiation were depressed in the spleens of CB-17 Icr +/ + mice, but not in severe combined immunodeficiency mice. These data suggest that DNA-dependent protein kinase might play a major role in radioadaptation induced by pre-irradiation with a low dose in mice spleen. We expect that the present findings will provide useful information in the health care of space crews.

  16. Low-dose laser acupuncture for non-specific chronic low back pain: a double-blind randomised controlled trial

    PubMed Central

    Glazov, Gregory; Yelland, Michael; Emery, Jon

    2014-01-01

    Objective To determine if infrared laser acupuncture (LA) may have a specific effect in reducing pain and disability in treatment of chronic low back pain (LBP). Methods This was a double-blind sham laser controlled trial performed in general practices in Perth, Western Australia. The participants were 144 adults with chronic non-specific LBP. They were randomised to receive eight once-weekly treatments. Laser machines (20 mW, 840 nm diode, power density 0.1 W/cm2) stimulated points in three treatment groups: sham (0 joules/point), low dose (0.2 J/point) and high dose (0.8 joules/point). Participants were followed-up at 1 and 6 weeks, and 6 and 12 months post treatment. Primary outcomes were pain (Numerical Pain Rating Scale (NPRS)) and disability (Oswestry Disability Inventory (ODI)) at 6 weeks post treatment. Secondary outcomes included numerical rating scale for limitation of activity, global assessment of improvement, analgesic usage and adverse effects after treatment. Results The analysis showed no difference between sham and the laser groups at 6 weeks for pain or disability. There was a significant reduction in mean pain and disability in all groups at 6 weeks (p<0.005); NPRS: sham (−1.5 (95% CI −2.1 to −0.8)), low dose (−1.3 (−2.0 to −0.8)), high dose (−1.1 (−1.7 to −0.5)). ODI: sham (−4.0 (−7.1 to −1.0)), low dose (−4.1, (−6.7 to −1.5)), high dose (−2.6 (−5.7 to 0.5)). All secondary outcomes also showed clinical improvement over time but with no differences between groups. Conclusions LA using energy density range (0–4 J/cm2) for the treatment of chronic non-specific LBP resulted in clinical improvement unrelated to laser stimulation. Trial registration http://www.anzctr.org.au ACTRN12610000043033. PMID:24280948

  17. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

    NASA Technical Reports Server (NTRS)

    Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

  18. FT-IR spectroscopy assessment of aesthetic dental materials irradiated with low-dose therapeutic ionizing radiation

    NASA Astrophysics Data System (ADS)

    Cruz, A. D.; Almeida, S. M.; Rastelli, A. N. S.; Bagnato, V. S.; Byscolo, F. N.

    2009-03-01

    The aim of the present study was to evaluate the effects of low-dose therapeutic ionizing radiation on different aesthetic dental materials. Forty five specimens ( n = 45) of three different aesthetic restorative materials were prepared and randomly divided into five groups: G1 (control group); G2, G3, G4, G5 experimental groups irradiated respectively with 0.25, 0.50, 0.75, and 1.00 Gy of gamma radiation by the 60Co teletherapy machine. Chemical analyses were performed using a FT-IR Nicolet 520 spectrophotometer with reflectance diffuse technique. Even a minimal exposition at ionizing radiation in therapeutic doses can provide chemical changes on light-cured composite resins. The three studied restorative materials showed changes after exposure at gamma radiation, however the increase of the radiation dose did not contribute to an increase in this effect.

  19. A Single Low Dose of Proton Radiation Induces Long-Term Behavioral and Electrophysiological Changes in Mice.

    PubMed

    Bellone, John A; Rudobeck, Emil; Hartman, Richard E; Szücs, Attila; Vlkolinský, Roman

    2015-08-01

    Astronauts traveling outside Earth's magnetosphere risk exposure to charged particle radiation that may cause neurophysiological changes and behavioral deficits. Although proton particles comprise a large portion of the space radiation environment, little has been published on the effects of low-dose proton radiation on central nervous system function. In the current study, we irradiated young male mice with 0.5 Gy 150 MeV protons and assessed the effects on behavior and hippocampal neurophysiology. Spatial learning ability, a sensitive behavioral marker of hippocampal damage, was assessed using the water maze and Barnes maze before irradiation and repeatedly 3 and 6 months after irradiation. Evoked field excitatory postsynaptic potentials (fEPSPs) and population spikes, long-term potentiation (LTP) and spontaneous oscillations (SOs) triggered by incubation with Mg(2+)-free media (reflecting interictal epileptiform activity) were assessed 9 months after irradiation in vitro in hippocampal slice preparations. Irradiated mice exhibited impaired reversal learning in the water maze compared to control mice 6 months after irradiation. Proton radiation did not affect LTP, but significantly increased fEPSP slopes and reduced the incidence of SOs 9 months after irradiation. These findings suggest that a single exposure to low-dose proton radiation can increase synaptic excitability and suppress the propensity for epileptiform activity. Such findings of functional alterations in the irradiated mouse hippocampus have implications for extended manned space missions planned in the near future. PMID:26207690

  20. Caffeine induces a second wave of apoptosis after low dose-rate gamma radiation of HL-60 cells.

    PubMed

    Vávrová, Jirina; Mareková-Rezácová, Martina; Vokurková, Doris; Szkanderová, Sylva; Psutka, Jan

    2003-10-01

    Most cell lines that lack functional p53 protein are arrested in the G(2) phase of the cell cycle due to DNA damage. It was previously found that the human promyelocyte leukemia cells HL-60 (TP53 negative) that had been exposed to ionizing radiation at doses up to 10 Gy were arrested in the G(2) phase for a period of 24 h. The radioresistance of HL-60 cells that were exposed to low dose-rate gamma irradiation of 3.9 mGy/min, which resulted in a pronounced accumulation of the cells in the G(2) phase during the exposure period, increased compared with the radioresistance of cells that were exposed to a high dose-rate gamma irradiation of 0.6 Gy/min. The D(0) value (i.e. the radiation dose leading to 37% cell survival) for low dose-rate radiation was 3.7 Gy and for high dose-rate radiation 2.2 Gy. In this study, prevention of G(2) phase arrest by caffeine (2 mM) and irradiation of cells with low dose-rate irradiation in all phases of the cell cycle proved to cause radiosensitization (D(0)=2.2 Gy). The irradiation in the presence of caffeine resulted in a second wave of apoptosis on days 5-7 post-irradiation. Caffeine-induced apoptosis occurring later than day 7 post-irradiation is postulated to be a result of unscheduled DNA replication and cell cycle progress.

  1. Mechanisms underlying the adaptive response against spontaneous neoplastic transformation induced by low doses of low LET radiation, Final Technical Report

    SciTech Connect

    J. Leslie Redpath, Ph.D.

    2006-01-23

    The goal of this project was to investigate mechanisms underlying the adaptive response seen following exposure of HeLa x skin fibroblast human hybrid cells to low doses of low LET radiation. It was proposed to investigate the contributions of three possible mechanisms. These were: 1. Upregulation of cellular antioxidant status. 2. Upregulation of DNA repair. 3. Upregulation of gap junction intracellular communication. We have completed the study of the role of upregulation of reduced glutathione (GSH) as a possible mechanism underlying our observed suppression of transformation frequency at low radiation doses. We have also completed our study of the possible role of upregulation of DNA repair in the observed adaptive response against neoplastic transformation. We concluded that upregulation of DNA repair may be more important in modulating transformation at the higher dose. A manuscript describing the above studies has been submitted published in Carcinogenesis 24:1961-1965, 2003. Finally, we have completed two studies of the possible role of upregulation of gap junction intercellular communication (GJIC) in modulating transformation frequency at low doses of low LET radiation. This research was published in Radiation Research 162:646-654, 2004. In order to optimize the opportunity for GJIC, we then carried out a study where confluent cultures were irradiated. The results indicated, that while the degree of low dose suppression was somewhat reduced compared to that seen for subconfluent cultures, it was not completely absent. This research has been submitted for publication. Our research program was of sufficient interest to generate two invited reviews, and five invited presentations.

  2. Sustained improvement of motor function in hemiparkinsonian rats chronically treated with low doses of caffeine or trihexyphenidyl.

    PubMed

    Bata-García, José L; Villanueva-Toledo, Jairo; Gutiérrez-Ospina, Gabriel; Alvarez-Cervera, Fernando J; Heredia-López, Francisco J; Góngora-Alfaro, José L

    2007-01-01

    The effects of chronic oral treatment with low doses of caffeine (1-3 mg/kg) and trihexyphenidyl (0.1-0.2 mg/kg) were tested on hemiparkinsonian rats, which received the following treatments in a counterbalanced order: vehicle, caffeine, trihexyphenidyl, and caffeine plus trihexyphenidyl. Three preclinical models were used: the stepping test, the cylinder test, and the staircase test. Compared to pre-lesion values, the forepaw contralateral to the dopamine-denervated side showed impaired stepping, fewer wall contacts in the cylinder test, and fewer pellets retrieved in the staircase test. In the stepping test both doses of caffeine produced a complete recovery of motor function (100%), whereas the effect of trihexyphenidyl was less intense (77-80%). In this same test the maximal effect of drugs did not develop tolerance during 2-3 weeks, and was completely reversible after drug cessation. In the cylinder test only the wall contacts performed simultaneously with both forepaws were significantly increased by caffeine (3 mg/kg) and trihexyphenidyl (0.2 mg/kg), and this effect was also reversible. In the staircase test none of the treatments improved food pellet retrieval with the contralateral forepaw. Altogether, these results show that chronic treatment with caffeine, at doses similar to daily human consumption, produces a sustained improvement in the use of the contralateral forelimb in unilaterally 6-hydroxydopamine denervated rats, without the development of tolerance. Although the combined administration of caffeine plus trihexyphenidyl showed no synergism in these models, the results suggest that low doses of caffeine (1-3 mg/kg/day) could be of therapeutic value for the reversal of motor symptoms in parkinsonian patients.

  3. Chronic Internal Exposure to Low Dose 137Cs Induces Positive Impact on the Stability of Atherosclerotic Plaques by Reducing Inflammation in ApoE-/- Mice.

    PubMed

    Le Gallic, Clélia; Phalente, Yohann; Manens, Line; Dublineau, Isabelle; Benderitter, Marc; Gueguen, Yann; Lehoux, Stephanie; Ebrahimian, Teni G

    2015-01-01

    After Chernobyl and Fukushima Daï Chi, two major nuclear accidents, large amounts of radionuclides were released in the environment, mostly caesium 137 (137Cs). Populations living in contaminated territories are chronically exposed to radionuclides by ingestion of contaminated food. However, questions still remain regarding the effects of low dose ionizing radiation exposure on the development and progression of cardiovascular diseases. We therefore investigated the effects of a chronic internal exposure to 137Cs on atherosclerosis in predisposed ApoE-/- mice. Mice were exposed daily to 0, 4, 20 or 100 kBq/l 137Cs in drinking water, corresponding to range of concentrations found in contaminated territories, for 6 or 9 months. We evaluated plaque size and phenotype, inflammatory profile, and oxidative stress status in different experimental groups. Results did not show any differences in atherosclerosis progression between mice exposed to 137Cs and unexposed controls. However, 137Cs exposed mice developed more stable plaques with decreased macrophage content, associated with reduced aortic expression of pro-inflammatory factors (CRP, TNFα, MCP-1, IFNγ) and adhesion molecules (ICAM-1, VCAM-1 and E-selectin). Lesions of mice exposed to 137Cs were also characterized by enhanced collagen and smooth muscle cell content, concurrent with reduced matrix metalloproteinase MMP8 and MMP13 expression. These results suggest that low dose chronic exposure of 137Cs in ApoE-/- mice enhances atherosclerotic lesion stability by inhibiting pro-inflammatory cytokine and MMP production, resulting in collagen-rich plaques with greater smooth muscle cell and less macrophage content. PMID:26046630

  4. Chronic Internal Exposure to Low Dose 137Cs Induces Positive Impact on the Stability of Atherosclerotic Plaques by Reducing Inflammation in ApoE-/- Mice

    PubMed Central

    Le Gallic, Clélia; Phalente, Yohann; Manens, Line; Dublineau, Isabelle; Benderitter, Marc; Gueguen, Yann; Lehoux, Stephanie; Ebrahimian, Teni G.

    2015-01-01

    After Chernobyl and Fukushima Daï Chi, two major nuclear accidents, large amounts of radionuclides were released in the environment, mostly caesium 137 (137Cs). Populations living in contaminated territories are chronically exposed to radionuclides by ingestion of contaminated food. However, questions still remain regarding the effects of low dose ionizing radiation exposure on the development and progression of cardiovascular diseases. We therefore investigated the effects of a chronic internal exposure to 137Cs on atherosclerosis in predisposed ApoE-/- mice. Mice were exposed daily to 0, 4, 20 or 100 kBq/l 137Cs in drinking water, corresponding to range of concentrations found in contaminated territories, for 6 or 9 months. We evaluated plaque size and phenotype, inflammatory profile, and oxidative stress status in different experimental groups. Results did not show any differences in atherosclerosis progression between mice exposed to 137Cs and unexposed controls. However, 137Cs exposed mice developed more stable plaques with decreased macrophage content, associated with reduced aortic expression of pro-inflammatory factors (CRP, TNFα, MCP-1, IFNγ) and adhesion molecules (ICAM-1, VCAM-1 and E-selectin). Lesions of mice exposed to 137Cs were also characterized by enhanced collagen and smooth muscle cell content, concurrent with reduced matrix metalloproteinase MMP8 and MMP13 expression. These results suggest that low dose chronic exposure of 137Cs in ApoE-/- mice enhances atherosclerotic lesion stability by inhibiting pro-inflammatory cytokine and MMP production, resulting in collagen-rich plaques with greater smooth muscle cell and less macrophage content. PMID:26046630

  5. Delayed effects of low-dose radiation on cellular immunity in atomic bomb survivors residing in the United States.

    PubMed

    Bloom, E T; Akiyama, M; Kusunoki, Y; Makinodan, T

    1987-05-01

    Several parameters of cellular immune function were assessed among persons who survived the 1945 atomic bombs in Hiroshima and Nagasaki but who now reside in the United States. The subjects in this study were exposed to various low doses (T65D) of radiation at the time of the bomb. More than half received an estimated 0 Gy (S0 group). Of those exposed to more radiation (S+ group), nearly 90% received less than 0.50 Gy (50 rad). Lymphocytes were isolated from the peripheral blood of these individuals and were assessed for the following parameters of cellular immunity: mitogenic response to phytohemagglutinin, mitogenic response to allogeneic lymphocytes, natural cell-mediated cytotoxicity (NCMC), and interferon production. In every case, the response of the S+ group was greater than that of the S0 group, although only the difference for NCMC was statistically significant. Results of studies presently being performed on A-bomb survivors residing in Hiroshima do not confirm this difference. Therefore, it is difficult to say whether the increase in natural cytotoxicity observed among the American and not the Japanese A-bomb survivors exposed to very low doses of radiation is a hormetic effect which was modulated by post-radiation environmental conditions or a result of selective migration.

  6. Low Dose Radiation Response Curves, Networks and Pathways in Human Lymphoblastoid Cells Exposed from 1 to 10 cGy of Acute Gamma Radiation

    SciTech Connect

    Wyrobek, A. J.; Manohar, C. F.; Nelson, D. O.; Furtado, M. R.; Bhattacharya, M. S.; Marchetti, F.; Coleman, M.A.

    2011-04-18

    We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of {approx}80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

  7. Regulation of the Low Dose Radiation Paracrine-Specific Anchorage-Independent Growth Response by Annexin A2

    SciTech Connect

    Weber, Thomas J.; Opresko, Lee K.; Waisman, David M.; Newton, Gregory J.; Quesenberry, Ryan D.; Bollinger, Nikki; Moore, Ronald J.; Smith, Richard D.

    2009-07-13

    ABSTRACT-Here we identify release of annexin A2 into the culture medium in response to low dose X-ray radiation exposure and establish functional linkages to an established paracrine factor-mediated anchorage-independent growth response. Using a standard bicameral coculture model, we observe that annexin A2 levels associated with non-irradiated neighboring cells seeded in the lower chamber (annexin A2 silenced [shRNA] JB6 cells) are increased upon coculture with irradiated (10-50 cGy) JB6 cells seeded in the upper chamber, relative to coculture with sham exposed JB6 cells seeded in the upper chamber, suggesting that annexin A2 released into the medium is capable of communicating in a paracrine fashion. Using a previously established coculture model, we observed that the paracrine factor-mediated anchorage-independent growth response to low dose X-ray radiation is markedly reduced when irradiated annexin A2 silenced (shRNA) JB6 cells are used, relative to coculture with irradiated annexin A2 competent vector control counterparts. These observations suggest that annexin A2 is functionally linked to the radiation paracrine factor-specific anchorage-independent growth response in JB6 cells.

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

    SciTech Connect

    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.

  9. Mutations of the human interferon alpha-2b (hIFNα-2b) gene in low-dose natural terrestrial ionizing radiation exposed dwellers.

    PubMed

    Shahid, Saman; Mahmood, Nasir; Chaudhry, Muhammad Nawaz; Ahmad, Nauman

    2015-12-01

    Natural terrestrial ionizing radiations emerge from uranium deposits and can impact human tissues by affecting DNA bases which constitute genes. Human interferon alpha-2b (hIFNα-2b) gene synthesizes a protein which exhibits anticancerous, immunomodulatory, anti-proliferative and antiviral properties. This research aimed to find out hIFNα-2b gene mutations for those residents who were chronically exposed to low-dose natural terrestrial ionizing radiations. The gene amplifications was done through PCR technique and gene mutations were identified by bioinformatics in order to conclude as to how mutations identified in hIFNα-2b gene sequences will lead to alterations in the hIFNα-2b protein in radiation exposed residents. The range of radiation dose exposure was 0.4383-4.55832 (mSv/y) for the selected radiation exposed locations which were having uranium mineralization. Mutations (24%) in hIFNα-2b gene shows that some of the radiation exposed inhabitants were having a modulated immune response. The CBC (Complete Blood Count) parameters: WBC (White Blood Cells), MCH (Mean Corpuscular Hemoglobin), MCHC (MCH Concentration) and PLT (Platelets) on average were below the normal range in 24% radiation exposed subjects who were having hIFNα-2b gene mutations. Immunomodulation is observed by the mixed trend of either lymphocytosis or lymphopenia and neutropenia or neutrophilia in the exposed population. Thus, a radioactive exposure from uranium can affect the immune system and can induce mutations.

  10. Response of the seminiferous epithelium of the mouse exposed to low dose high energy (HZE) and electromagnetic radiation.

    PubMed

    Philpott, D E; Sapp, W; Williams, C; Stevenson, J; Corbett, R; Black, S

    1983-01-01

    This study was undertaken to observe the response of a rapidly dividing cell population (spermatogonial) to Helium and Argon ions as compared to x-rays. Low doses (below 100 rads) were used to more nearly simulate radiation encountered during space missions. The methods used proved compatible for both light and electron microscope studies. The average relative biological effectiveness (RBE) for Helium ions is 1, while Argon is twice as effective in killing spermatogonial cells. Part of this mixed population of cells exhibits a higher sensitivity to radiation below 15 rads. Quantitation of the radiation effects by counting the necrotic cells is not feasible because of their rapid removal, therefore all measurements were done using the surviving fraction (S/So) of spermatogonial cells.

  11. Charophyte electrogenesis as a biomarker for assessing the risk from low-dose ionizing radiation to a single plant cell.

    PubMed

    Sevriukova, Olga; Kanapeckaite, Auste; Lapeikaite, Indre; Kisnieriene, Vilma; Ladygiene, Rima; Sakalauskas, Vidmantas

    2014-10-01

    The impact of low-dose ionizing radiation on the electrical signalling pattern and membrane properties of the characea Nitellopsis obtusa was examined using conventional glass-microelectrode and voltage-clamp techniques. The giant cell was exposed to a ubiquitous radionuclide of high biological importance - tritium - for low-dose irradiation. Tritium was applied as tritiated water with an activity concentration of 15 kBq L(-1) (an external dose rate that is approximately 0.05 μGy h(-1) above the background radiation level); experiments indicated that this was the lowest effective concentration. Investigating the dynamics of electrical excitation of the plasma membrane (action potential) showed that exposing Characeae to tritium for half an hour prolonged the repolarization phase of the action potential by approximately 35%: the repolarization rate decreased from 39.2 ± 3.1 mV s(-1) to 25.5 ± 1,8 mV s(-1) due to tritium. Voltage-clamp measurements showed that the tritium exposure decreased the Cl(-) efflux and Ca(2+) influx involved in generating an action potential by approximately 27% (Δ = 12.4 ± 1.1 μA cm(-2)) and 64% (Δ = -5.3 ± 0.4 μA cm(-2)), respectively. The measured alterations in the action potential dynamics and in the chloride and calcium ion transport due to the exogenous low-dose tritium exposure provide the basis for predicting possible further impairments of plasma membrane regulatory functions, which subsequently disturb essential physiological processes of the plant cell. PMID:24858694

  12. Reducing the low-dose lung radiation for central lung tumors by restricting the IMRT beams and arc arrangement.

    PubMed

    Rosca, Florin; Kirk, Michael; Soto, Daniel; Sall, Walter; McIntyre, James

    2012-01-01

    To compare the extent to which 7 different radiotherapy planning techniques for mediastinal lung targets reduces the lung volume receiving low doses of radiation. Thirteen non-small cell lung cancer patients with targets, including the mediastinal nodes, were identified. Treatment plans were generated to both 60- and 74-Gy prescription doses using 7 different planning techniques: conformal, hybrid conformal/intensity-modulated radiation treatment (IMRT), 7 equidistant IMRT beams, 2 restricted beam IMRT plans, a full (360°) modulated arc, and a restricted modulated arc plan. All plans were optimized to reduce total lung V5, V10, and V20 volumes, while meeting normal tissue and target coverage constraints. The mean values for the 13 patients are calculated for V5, V10, V20, V(ave), V0-20, and mean lung dose (MLD) lung parameters. For the 74-Gy prescription dose, the mean lung V10 was 42.7, 43.6, 48.2, 56.6, 57, 55.8, and 54.1% for the restricted ±36° IMRT, restricted modulated arc, restricted ±45° IMRT, full modulated arc, hybrid conformal/IMRT, equidistant IMRT, and conformal plans, respectively. A similar lung sparing hierarchy was found for the 60-Gy prescription dose. For the treatment of central lung targets, the ±36° restricted IMRT and restricted modulated arc planning techniques are superior in lowering the lung volume treated to low dose, as well as in minimizing MLD, followed by the ±45° restricted IMRT plan. All planning techniques that allow the use of lateral or lateral/oblique beams result in spreading the low dose over a higher lung volume. The area under the lung dose-volume histogram curve below 20 Gy, V0-20, is proposed as an alternative to individual V(dose) parameters, both as a measure of lung sparing and as a parameter to be minimized during IMRT optimization. PMID:22189028

  13. Charophyte electrogenesis as a biomarker for assessing the risk from low-dose ionizing radiation to a single plant cell.

    PubMed

    Sevriukova, Olga; Kanapeckaite, Auste; Lapeikaite, Indre; Kisnieriene, Vilma; Ladygiene, Rima; Sakalauskas, Vidmantas

    2014-10-01

    The impact of low-dose ionizing radiation on the electrical signalling pattern and membrane properties of the characea Nitellopsis obtusa was examined using conventional glass-microelectrode and voltage-clamp techniques. The giant cell was exposed to a ubiquitous radionuclide of high biological importance - tritium - for low-dose irradiation. Tritium was applied as tritiated water with an activity concentration of 15 kBq L(-1) (an external dose rate that is approximately 0.05 μGy h(-1) above the background radiation level); experiments indicated that this was the lowest effective concentration. Investigating the dynamics of electrical excitation of the plasma membrane (action potential) showed that exposing Characeae to tritium for half an hour prolonged the repolarization phase of the action potential by approximately 35%: the repolarization rate decreased from 39.2 ± 3.1 mV s(-1) to 25.5 ± 1,8 mV s(-1) due to tritium. Voltage-clamp measurements showed that the tritium exposure decreased the Cl(-) efflux and Ca(2+) influx involved in generating an action potential by approximately 27% (Δ = 12.4 ± 1.1 μA cm(-2)) and 64% (Δ = -5.3 ± 0.4 μA cm(-2)), respectively. The measured alterations in the action potential dynamics and in the chloride and calcium ion transport due to the exogenous low-dose tritium exposure provide the basis for predicting possible further impairments of plasma membrane regulatory functions, which subsequently disturb essential physiological processes of the plant cell.

  14. Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

    NASA Technical Reports Server (NTRS)

    Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

    2000-01-01

    Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

  15. High and low dose radiation effects on mammary adenocarcinoma cells – an epigenetic connection

    PubMed Central

    Luzhna, Lidia; Filkowski, Jody; Kovalchuk, Olga

    2016-01-01

    The successful treatment of cancer, including breast cancer, depends largely on radiation therapy and proper diagnostics. The effect of ionizing radiation on cells and tissues depends on the radiation dose and energy level, but there is insufficient evidence concerning how tumor cells respond to the low and high doses of radiation that are often used in medical diagnostic and treatment modalities. The purpose of this study was to investigate radiation-induced gene expression changes in the MCF-7 breast adenocarcinoma cell line. Using microarray technology tools, we were able to screen the differential gene expressions profiles between various radiation doses applied to MCF-7 cells. Here, we report the substantial alteration in the expression level of genes after high-dose treatment. In contrast, no dramatic gene expression alterations were noticed after the application of low and medium doses of radiation. In response to a high radiation dose, MCF-7 cells exhibited down-regulation of biological pathways such as cell cycle, DNA replication, and DNA repair and activation of the p53 pathway. Similar dose-dependent responses were seen on the epigenetic level, which was tested by a microRNA expression analysis. MicroRNA analysis showed dose-dependent radiation-induced microRNA expression alterations that were associated with cell cycle arrest and cell death. An increased rate of apoptosis was determined by an Annexin V assay. The results of this study showed that high doses of radiation affect gene expression genetically and epigenetically, leading to alterations in cell cycle, DNA replication, and apoptosis. PMID:27226982

  16. Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes.

    PubMed

    Coleman, Matthew A; Sasi, Sharath P; Onufrak, Jillian; Natarajan, Mohan; Manickam, Krishnan; Schwab, John; Muralidharan, Sujatha; Peterson, Leif E; Alekseyev, Yuriy O; Yan, Xinhua; Goukassian, David A

    2015-12-01

    There are 160,000 cancer patients worldwide treated with particle radiotherapy (RT). With the advent of proton, and high (H) charge (Z) and energy (E) HZE ionizing particle RT, the cardiovascular diseases risk estimates are uncertain. In addition, future deep space exploratory-type missions will expose humans to unknown but low doses of particle irradiation (IR). We examined molecular responses using transcriptome profiling in left ventricular murine cardiomyocytes isolated from mice that were exposed to 90 cGy, 1 GeV proton ((1)H) and 15 cGy, 1 GeV/nucleon iron ((56)Fe) over 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the IR response and time after exposure, with (56)Fe-IR showing the greatest level of gene modulation. (1)H-IR showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses, and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Validation of the signal transduction network by protein analysis and gel shift assay showed that particle IR clearly regulates a long-lived signaling mechanism for ERK1/2, p38 MAPK signaling and identified NFATc4, GATA4, STAT3, and NF-κB as regulators of the response at specific time points. These data suggest that the molecular responses and gene expression to (56)Fe-IR in cardiomyocytes are unique and long-lasting. Our study may have significant implications for the efforts of National Aeronautics and Space Administration to develop heart disease risk estimates for astronauts and for patients receiving conventional and particle RT via identification of specific HZE-IR molecular markers.

  17. Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes.

    PubMed

    Coleman, Matthew A; Sasi, Sharath P; Onufrak, Jillian; Natarajan, Mohan; Manickam, Krishnan; Schwab, John; Muralidharan, Sujatha; Peterson, Leif E; Alekseyev, Yuriy O; Yan, Xinhua; Goukassian, David A

    2015-12-01

    There are 160,000 cancer patients worldwide treated with particle radiotherapy (RT). With the advent of proton, and high (H) charge (Z) and energy (E) HZE ionizing particle RT, the cardiovascular diseases risk estimates are uncertain. In addition, future deep space exploratory-type missions will expose humans to unknown but low doses of particle irradiation (IR). We examined molecular responses using transcriptome profiling in left ventricular murine cardiomyocytes isolated from mice that were exposed to 90 cGy, 1 GeV proton ((1)H) and 15 cGy, 1 GeV/nucleon iron ((56)Fe) over 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the IR response and time after exposure, with (56)Fe-IR showing the greatest level of gene modulation. (1)H-IR showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses, and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Validation of the signal transduction network by protein analysis and gel shift assay showed that particle IR clearly regulates a long-lived signaling mechanism for ERK1/2, p38 MAPK signaling and identified NFATc4, GATA4, STAT3, and NF-κB as regulators of the response at specific time points. These data suggest that the molecular responses and gene expression to (56)Fe-IR in cardiomyocytes are unique and long-lasting. Our study may have significant implications for the efforts of National Aeronautics and Space Administration to develop heart disease risk estimates for astronauts and for patients receiving conventional and particle RT via identification of specific HZE-IR molecular markers. PMID:26408534

  18. Differential Response and Priming Dose Effect on the Proteome of Human Fibroblast and Stem Cells Induced by Exposure to Low Doses of Ionizing Radiation.

    PubMed

    Hauptmann, Monika; Haghdoost, Siamak; Gomolka, Maria; Sarioglu, Hakan; Ueffing, Marius; Dietz, Anne; Kulka, Ulrike; Unger, Kristian; Babini, Gabriele; Harms-Ringdahl, Mats; Ottolenghi, Andrea; Hornhardt, Sabine

    2016-03-01

    It has been suggested that a mechanistic understanding of the cellular responses to low dose and dose rate may be valuable in reducing some of the uncertainties involved in current risk estimates for cancer- and non-cancer-related radiation effects that are inherited in the linear no-threshold hypothesis. In this study, the effects of low-dose radiation on the proteome in both human fibroblasts and stem cells were investigated. Particular emphasis was placed on examining: 1. the dose-response relationships for the differential expression of proteins in the low-dose range (40-140 mGy) of low-linear energy transfer (LET) radiation; and 2. the effect on differential expression of proteins of a priming dose given prior to a challenge dose (adaptive response effects). These studies were performed on cultured human fibroblasts (VH10) and human adipose-derived stem cells (ADSC). The results from the VH10 cell experiments demonstrated that low-doses of low-LET radiation induced unique patterns of differentially expressed proteins for each dose investigated. In addition, a low priming radiation dose significantly changed the protein expression induced by the subsequent challenge exposure. In the ADSC the number of differentially expressed proteins was markedly less compared to VH10 cells, indicating that ADSC differ in their intrinsic response to low doses of radiation. The proteomic results are further discussed in terms of possible pathways influenced by low-dose irradiation. PMID:26934482

  19. Mechanistic and quantitative studies of bystander response in 3D tissues for low-dose radiation risk estimations

    SciTech Connect

    Amundson, Sally A.

    2013-06-12

    We have used the MatTek 3-dimensional human skin model to study the gene expression response of a 3D model to low and high dose low LET radiation, and to study the radiation bystander effect as a function of distance from the site of irradiation with either alpha particles or low LET protons. We have found response pathways that appear to be specific for low dose exposures, that could not have been predicted from high dose studies. We also report the time and distance dependent expression of a large number of genes in bystander tissue. the bystander response in 3D tissues showed many similarities to that described previously in 2D cultured cells, but also showed some differences.

  20. Foods for a Mission to Mars: Investigations of Low-Dose Gamma Radiation Effects

    NASA Technical Reports Server (NTRS)

    Gandolph, J.; Shand, A.; Stoklosa, A.; Ma, A.; Weiss, I.; Alexander, D.; Perchonok, M.; Mauer, L. J.

    2007-01-01

    Food must be safe, nutritious, and acceptable throughout a long duration mission to maintain the health, well-being, and productivity of the astronauts. In addition to a developing a stable pre-packaged food supply, research is required to better understand the ability to convert edible biomass into safe, nutritious, and acceptable food products in a closed system with many restrictions (mass, volume, power, crew time, etc.). An understanding of how storage conditions encountered in a long-term space mission, such as elevated radiation, will impact food quality is also needed. The focus of this project was to contribute to the development of the highest quality food system possible for the duration of a mission, considering shelf-stable extended shelf-life foods, bulk ingredients, and crops to be grown in space. The impacts of space-relevant radiation doses on food, bulk ingredient, and select candidate crop quality and antioxidant capacity were determined. Interestingly, increasing gamma-radiation doses (0 to 1000 Gy) did not always increase dose-related effects in foods. Intermediate radiation doses (10 to 800Gy) often had significantly larger impact on the stability of bulk ingredient oils than higher (1000Gy) radiation doses. Overall, most food, ingredient, and crop systems investigated showed no significant differences between control samples and those treated with 3 Gy of gamma radiation (the upper limit estimated for a mission to Mars). However, this does not mean that all foods will be stable for 3-5 years, nor does it mean that foods are stable to space radiation comprising more than gamma rays.

  1. Inhibition of gastric secretion in guinea pig by relatively low dose ionizing radiation

    SciTech Connect

    Batzri, S.; Catravas, G.

    1988-11-01

    We evaluated the effect of a single dose of ionizing radiation on gastric secretion in awake guinea pigs equipped with a permanent gastric cannula. Changes in gastric secretion were measured using a dye dilution technique. Infusion of histamine increased acid and fluid output and there was a positive correlation (r = 0.93) between the two. Total body irradiation with 400 cGy, like cimetidine, suppressed acid and fluid secretion under basal conditions and during histamine stimulation by 50-90%. Recovery from the radiation damage was only partial after one week. Irradiation inhibited the rise in gastric juice volume during histamine stimulation and also reduced the normal gain in body weight of the guinea pig. These results demonstrate that ionizing radiations have an immediate and long lasting effects on the gastric mucosal function of the guinea pig.

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

    PubMed

    Mothersill, Carmel; Smith, Richard W; Heier, Lene Sørlie; Teien, Hans-Christian; Lind, Ole Christian; Land, Ole Christian; Seymour, Colin B; Oughton, Deborah; Salbu, Brit

    2014-03-01

    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.

  3. Low Dose Radiation-Induced Genome and Epigenome Instability Symposium and Epigenetic Mechanisms, DNA Repair, and Chromatin Symposium at the EMS 2008 Annual Meeting - October 2008

    SciTech Connect

    Morgan, William F; Kovalchuk, Olga; Dolinoy, Dana C; Dubrova, Yuri E; Coleman, Matthew A; Schär, Primo; Pogribny, Igor; Hendzel, Michael

    2010-02-19

    The Low Dose Radiation Symposium thoughtfully addressed ionizing radiation non-mutational but transmissable alterations in surviving cells. Deregulation of epigenetic processes has been strongly implicated in carcinogenesis, and there is increasing realization that a significant fraction of non-targeted and adaptive mechanisms in response to ionizing radiation are likely to be epigenetic in nature. Much remains to be learned about how chromatin and epigenetic regulators affect responses to low doses of radiation, and how low dose radiation impacts other epigenetic processes. The Epigenetic Mechanisms Symposium focused on on epigenetic mechanisms and their interplay with DNA repair and chromatin changes. Addressing the fact that the most well understood mediators of epigenetic regulation are histone modifications and DNA methylation. Low levels of radiation can lead to changes in the methylation status of certain gene promoters and the expression of DNA methyltransferases, However, epigenetic regulation can also involve changes in higher order chromosome structure.

  4. The Effect of Docetaxel (Taxotere®) on Human Gastric Cancer Cells Exhibiting Low-Dose Radiation Hypersensitivity

    PubMed Central

    Balcer-Kubiczek, Elizabeth K.; Attarpour, Mona; Wang, Jian Z.; Regine, William F.

    2008-01-01

    Low-dose radiation hypersensitivity (HRS) describes a phenomenon of excessive sensitivity to X ray doses <0.5 Gy. Docetaxel is a taxane shown to arrest cells in the G2/M phase of the cell cycle. Some previous studies suggested that HRS might result from the abrogation of the early G2 checkpoint arrest. First we tested whether HRS occurs in gastric cancer—derived cells, and whether pre-treatment of cells with low docetaxel concentrations can enhance the magnitude of HRS in gastric cancer cells. The results demonstrated HRS at ~0.3 Gy and the synergy between 0.3 Gy and docetaxel (3 nM for 24 h), and the additivity of other drug/dose combinations. The synergistic effect was associated with a significant docetaxel-induced G2 accumulation. Next, we evaluated in time-course experiments ATM kinase activity and proteins associated with the induction and maintenance of the early G2 checkpoint. The results of multi-immunoblot analysis demonstrate that HRS does not correlate with the ATM-dependent early G2 checkpoint arrest. We speculate that G2 checkpoint adaptation, a phenomenon associated with a prolonged cell cycle arrest, might be involved in HRS. Our results also suggest a new approach for the improvement the effectiveness of docetaxel-based radiotherapy using low doses per fraction. PMID:21892291

  5. Morphological and functional deterioration of the rat thyroid following chronic exposure to low-dose PCB118.

    PubMed

    Tang, Jin-Mei; Li, Wen; Xie, Yu-Chun; Guo, Hong-Wei; Cheng, Pei; Chen, Huan-Huan; Zheng, Xu-Qin; Jiang, Lin; Cui, Dai; Liu, Yun; Ding, Guo-Xian; Duan, Yu

    2013-11-01

    Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that can severely disrupt the synthesis and secretion of endocrine hormones. To investigate the effects of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on thyroid structure and function, 40 male Wistar rats were divided into 4 equal treatment groups and administered vehicle or one of three doses of PCB118. The experimental groups received intraperitoneal (i.p.) injection of 10, 100, or 1000μg/kg/day PCB118, 5 days per week for 13 weeks, whereas the control group was injected with corn oil (vehicle). Serum concentrations of free thyroxine (FT4), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) were measured by radioimmunoassays. Histopathological and ultrastructural changes in the thyroid were observed under light microscopy and transmission electron microscopy (TEM). The mRNA expression levels of the sodium-iodide symporter (NIS) and thyroglobulin (TG) were quantified by real-time PCR. Increasing doses of PCB118 resulted in progressively lower FT3, FT4 and TSH concentrations in serum. Injection of PCB118 at all doses led to histopathological deterioration of the thyroid characterized by follicular hyperplasia and expansion, shedding of epithelial cells and fibrinoid necrosis. Follicle cells exhibited swollen or vacuolated endoplasmic reticula, as revealed by TEM. Exposure to PCB118 also caused significant decreases in NIS and TG mRNA expression levels. Chronic exposure to low-dose PCB118 and other PCB congeners may be a significant risk factor for thyroid diseases. PMID:23557935

  6. Mammary carcinogenic effect of low-dose fission radiation in Wistar/Furth rats and its dependency on prolactin

    SciTech Connect

    Yokoro, K.; Sumi, C.; Ito, A.; Hamada, K.; Kanda, K.; Kobayashi, T.

    1980-06-01

    The mammary carcinogenic effect in rats of low-dose fission radiation and its dependency on prolactin were studied. A total of 141 female W/Fu rats were exposed to 4.8, 8.9, or 19.5 rads of fission radiation that had both fission neutrons of 2.0 million electron volts (MeV) and gamma ray components similar to those produced by the Hiroshima bomb. Only 1 of 48 rats (2.0%) developed mammary tumor (MT) after irradiation alone, whereas 20 of 48 rats (41.6%) developed MT's if prolactin was supplied shortly after irradiation by means of grafting of the prolactin-secreting pituitary tumor. Furthermore, MT's occurred in 11 of 45 rats (24.4%) treated wit prolactin as late as 12 months after irradiation, which suggested the long-term survival of radiation-induced dormant MT cells. A correlation was found between the development of MT and the elevation of serum prolactin level; most MT's appeared shortly after the grafted mammotropic pituitary tumor became palpable. The growth of MT's appeared to be promoted by prolactin in collaboration with ovarian hormones; the growth of adenocarcinomas was dependent on prolactin and ovarian hormones, whereas the growth of fibroadenomas appeared to be less hormone-dependent. Much higher bioiogic effectiveness, especially in the low-dose range, was found with 2.0-MeV fission neutrons compared with 14.1-MeV fast neutrons or 180-kilovolt peak X-rays in rat mammary carcinogenesis.

  7. Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

    SciTech Connect

    Minsky, B.D.; Cohen, A.M.; Kemeny, N.; Enker, W.E.; Kelsen, D.P.; Schwartz, G.; Saltz, L.; Dougherty, J.; Frankel, J.; Wiseberg, J. )

    1993-04-02

    The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily [times] 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs.

  8. Assessment of the Technologies for Molecular Biodosimetry for Human Low-Dose Radiation Exposure Symposium

    SciTech Connect

    Matthew A. Coleman Ph.D.; Narayani Ramakrishnan, Ph.D.; Sally A. Amundson; James D. Tucker, Ph.D.; Stephen D. Dertinger, Ph.D.; Natalia I. Ossetrova, Ph.D.; Tao Chen

    2009-11-16

    Exposure to ionizing radiation produces few immediate outwardly-visible clinical signs, yet, depending on dose, can severely damage vital physiological functions within days to weeks and produce long-lasting health consequences among survivors. In the event of a radiological accident, the rapid evaluation of the individual absorbed dose is paramount to discriminate the worried but unharmed from those individuals who must receive medical attention. Physical, clinical and biological dosimetry are usually combined for the best dose assessment. However, because of the practical limits of physical and clinical dosimetry, many attempts have been made to develop a dosimetry system based on changes in biological parameters, including techniques for hematology, biochemistry, immunology, cytogenetics, etc. Lymphocyte counts and chromosome aberrations analyses are among the methods that have been routinely used for estimating radiation dose. However, these assays require several days to a week to be completed and therefore cannot be used to obtain a fast estimate of the dose during the first few days after exposure when the information would be most critical for identifying victims of radiation accidents who could benefit the most by medical intervention. The steadily increasing sophistication in our understanding of the early biochemical responses of irradiated cells and tissues provides the opportunity for developing mechanism-based biosignatures of exposure. Compelling breakthroughs have been made in the technologies for genome-scale analysis of cellular transcriptional and proteomic profiles. There have also been major strides in the mechanistic understanding of the early events in DNA damage and radiation damage products, as well as in the cellular pathways that lead to radiation injury. New research with genomic- and proteomic-wide tools is showing that within minutes to hours after exposure to ionizing radiation protein machines are modified and activated, and large

  9. Divergent modification of low-dose ⁵⁶Fe-particle and proton radiation on skeletal muscle.

    PubMed

    Shtifman, Alexander; Pezone, Matthew J; Sasi, Sharath P; Agarwal, Akhil; Gee, Hannah; Song, Jin; Perepletchikov, Aleksandr; Yan, Xinhua; Kishore, Raj; Goukassian, David A

    2013-11-01

    It is unknown whether loss of skeletal muscle mass and function experienced by astronauts during space flight could be augmented by ionizing radiation (IR), such as low-dose high-charge and energy (HZE) particles or low-dose high-energy proton radiation. In the current study adult mice were irradiated whole-body with either a single dose of 15 cGy of 1 GeV/n ⁵⁶Fe-particle or with a 90 cGy proton of 1 GeV/n proton particles. Both ionizing radiation types caused alterations in the skeletal muscle cytoplasmic Ca²⁺ ([Ca²⁺]i) homeostasis. ⁵⁶Fe-particle irradiation also caused a reduction of depolarization-evoked Ca²⁺ release from the sarcoplasmic reticulum (SR). The increase in the [Ca²⁺]i was detected as early as 24 h after ⁵⁶Fe-particle irradiation, while effects of proton irradiation were only evident at 72 h. In both instances [Ca²⁺]i returned to baseline at day 7 after irradiation. All ⁵⁶Fe-particle irradiated samples revealed a significant number of centrally localized nuclei, a histologic manifestation of regenerating muscle, 7 days after irradiation. Neither unirradiated control or proton-irradiated samples exhibited such a phenotype. Protein analysis revealed significant increase in the phosphorylation of Akt, Erk1/2 and rpS6k on day 7 in ⁵⁶Fe-particle irradiated skeletal muscle, but not proton or unirradiated skeletal muscle, suggesting activation of pro-survival signaling. Our findings suggest that a single low-dose ⁵⁶Fe-particle or proton exposure is sufficient to affect Ca²⁺ homeostasis in skeletal muscle. However, only ⁵⁶Fe-particle irradiation led to the appearance of central nuclei and activation of pro-survival pathways, suggesting an ongoing muscle damage/recovery process. PMID:24131063

  10. Radiolytic yield of ozone in air for low dose neutron and x-ray/gamma-ray radiation

    NASA Astrophysics Data System (ADS)

    Cole, J.; Su, S.; Blakeley, R. E.; Koonath, P.; Hecht, A. A.

    2015-01-01

    Radiation ionizes surrounding air and produces molecular species, and these localized effects may be used as a signature of, and for quantification of, radiation. Low-level ozone production measurements from radioactive sources have been performed in this work to understand radiation chemical yields at low doses. The University of New Mexico AGN-201 M reactor was used as a tunable radiation source. Ozone levels were compared between reactor-on and reactor-off conditions, and differences (0.61 to 0.73 ppb) well below background levels were measured. Simulations were performed to determine the dose rate distribution and average dose rate to the air sample within the reactor, giving 35 mGy of mixed photon and neutron dose. A radiation chemical yield for ozone of 6.5±0.8 molecules/100 eV was found by a variance weighted average of the data. The different contributions of photons and neutrons to radiolytic ozone production are discussed.

  11. Oxidative Stress and Skeletal Health with Low-Dose, Low-LET (Linear Energy Transfer) Ionizing Radiation

    SciTech Connect

    Globus, Ruth K.

    2014-11-03

    We performed in vivo and in vitro experiments to accomplish the following specific aims of this project: 1) determine if low dose, low LET radiation affects skeletal remodeling at structural, cellular and molecular levels and 2) determine if low dose, low LET radiation modulates skeletal health during aging via oxidative mechanisms. A third aim is supported by NASA supplement to this DOE grant focusing on the influence of high LET radiation on bone. A series of experiments were conducted at the NASA Space Radiation Laboratory at Brookhaven, NSRL-BNL, using iron (56Fe) or a sequential exposure to protons / iron / protons, and separate experiments at NASA Ames Research Center (ARC) using 137Cs. The following provides a summary of key findings. (1) Exposure of nine-week old female mice to priming doses of gamma radiation (10cGy x 5) did not significantly affect bone volume/total volume (BV/TV) or microarchitecture as analyzed by 3D microcomputed tomography. As expected, exposure to the challenge dose of 2 Gy gamma irradiation resulted in significant decreases in BV/TV. The priming dose combined with the 2Gy challenge dose had no further effect on BV/TV compared to challenge dose alone, with the sole exception of the Structural Model Index (SMI). SMI reflects the ratio of rods-to-plates in cancellous bone tissue, such that higher SMI values indicate a tendency toward a weaker structure compared to lower SMI values. Mice treated with both priming and challenge dose had 25% higher SMI values compared to sham-irradiated controls and 7% higher values compared to mice treated with the challenge dose alone. Thus, although this priming regimen had relatively modest effects on cancellous tissue, the difference in SMI suggests this fractionated priming doses have adverse, rather than beneficial, effects on bone structure. (2) In 10-week old male mice, a single exposure to 100cGy of 137Cs reduces trabecular bone number and connectivity density by 20% and 36% respectively one

  12. Possible scenarios of the influence of low-dose ionizing radiation on neural functioning.

    PubMed

    Zakhvataev, Vladimir E

    2015-12-01

    Possible scenarios of the influence of ionizing radiation on neural functioning and the CNS are suggested. We argue that the radiation-induced bystander mechanisms associated with Ca(2+) flows, reactive nitrogen and oxygen species, and cytokines might lead to modulation of certain neuronal signaling pathways. The considered scenarios of conjugation of the bystander signaling and the neuronal signaling might result in modulation of certain synaptic receptors, neurogenesis, neurotransmission, channel conductance, synaptic signaling, different forms of neural plasticity, memory formation and storage, and learning. On this basis, corresponding new possible strategies for treating neurodegenerative deceases and mental disorders are proposed. The mechanisms considered might also be associated with neuronal survival and relevant to the treatment for brain injuries. At the same time, these mechanisms might be associated with detrimental effects and might facilitate the development of some neurological and psychiatric disorders. PMID:26526727

  13. Genetic radiation risks: a neglected topic in the low dose debate

    PubMed Central

    2016-01-01

    Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (Abomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down’s syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about

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

    PubMed

    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.

  15. Reducing the low-dose lung radiation for central lung tumors by restricting the IMRT beams and arc arrangement

    SciTech Connect

    Rosca, Florin

    2012-10-01

    To compare the extent to which 7 different radiotherapy planning techniques for mediastinal lung targets reduces the lung volume receiving low doses of radiation. Thirteen non-small cell lung cancer patients with targets, including the mediastinal nodes, were identified. Treatment plans were generated to both 60- and 74-Gy prescription doses using 7 different planning techniques: conformal, hybrid conformal/intensity-modulated radiation treatment (IMRT), 7 equidistant IMRT beams, 2 restricted beam IMRT plans, a full (360 Degree-Sign ) modulated arc, and a restricted modulated arc plan. All plans were optimized to reduce total lung V5, V10, and V20 volumes, while meeting normal tissue and target coverage constraints. The mean values for the 13 patients are calculated for V5, V10, V20, V{sub ave}, V0-20, and mean lung dose (MLD) lung parameters. For the 74-Gy prescription dose, the mean lung V10 was 42.7, 43.6, 48.2, 56.6, 57, 55.8, and 54.1% for the restricted {+-}36 Degree-Sign IMRT, restricted modulated arc, restricted {+-}45 Degree-Sign IMRT, full modulated arc, hybrid conformal/IMRT, equidistant IMRT, and conformal plans, respectively. A similar lung sparing hierarchy was found for the 60-Gy prescription dose. For the treatment of central lung targets, the {+-}36 Degree-Sign restricted IMRT and restricted modulated arc planning techniques are superior in lowering the lung volume treated to low dose, as well as in minimizing MLD, followed by the {+-}45 Degree-Sign restricted IMRT plan. All planning techniques that allow the use of lateral or lateral/oblique beams result in spreading the low dose over a higher lung volume. The area under the lung dose-volume histogram curve below 20 Gy, V0-20, is proposed as an alternative to individual V{sub dose} parameters, both as a measure of lung sparing and as a parameter to be minimized during IMRT optimization.

  16. Radiation Leukemogenesis: Applying Basic Science of Epidemiological Estimates of Low Dose Risks and Dose-Rate Effects

    SciTech Connect

    Hoel, D. G.

    1998-11-01

    The next stage of work has been to examine more closely the A-bomb leukemia data which provides the underpinnings of the risk estimation of CML in the above mentioned manuscript. The paper by Hoel and Li (Health Physics 75:241-50) shows how the linear-quadratic model has basic non-linearities at the low dose region for the leukemias including CML. Pierce et. al., (Radiation Research 123:275-84) have developed distributions for the uncertainty in the estimated exposures of the A-bomb cohort. Kellerer, et. al., (Radiation and Environmental Biophysics 36:73-83) has further considered possible errors in the estimated neutron values and with changing RBE values with dose and has hypothesized that the tumor response due to gamma may not be linear. We have incorporated his neutron model and have constricted new A-bomb doses based on his model adjustments. The Hoel and Li dose response analysis has also been applied using the Kellerer neutron dose adjustments for the leukemias. Finally, both Pierce's dose uncertainties and Kellerer neutron adjustments are combined as well as the varying RBE with dose as suggested by Rossi and Zaider and used for leukemia dose-response analysis. First the results of Hoel and Li showing a significantly improved fit of the linear-quadratic dose response by the inclusion of a threshold (i.e. low-dose nonlinearity) persisted. This work has been complete for both solid tumor as well as leukemia for both mortality as well as incidence data. The results are given in the manuscript described below which has been submitted to Health Physics.

  17. Low-dose radiation augments vasculogenesis signaling through HIF-1-dependent and -independent SDF-1 induction.

    PubMed

    Lerman, Oren Z; Greives, Matthew R; Singh, Sunil P; Thanik, Vishal D; Chang, Christopher C; Seiser, Natalie; Brown, Daniel J; Knobel, Denis; Schneider, Robert J; Formenti, Silvia C; Saadeh, Pierre B; Levine, Jamie P

    2010-11-01

    The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1α (HIF-1α) up-regulation in endothelial cells (ECs), a HIF-1α-independent up-regulation of stromal cell-derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1α and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect. While small interfering RNA silencing of HIF-1α mRNA and abolition of HIF-1α protein induction down-regulated SDF-1 induction by hypoxia alone, it had little effect on SDF-1 induction by IR, demonstrating an independent pathway. SDF-1-mediated EC migration in hypoxic and/or radiation-treated media showed IR induced strong SDF-1-dependent migration of ECs, augmented by hypoxia. IR activates a novel pathway stimulating EC migration directly through the expression of SDF-1 independent of HIF-1α induction. These observations might be exploited for stimulation of wound healing or controlling tumor angiogenesis. PMID:20631377

  18. Deterministic effect of lens at leukergy of patients who received low doses of ionising radiation.

    PubMed

    Yeltokova, M; Zharliganova, D; Shaidarov, M; Bakhtin, M; Kazymbet, P; Tel, L; Dossakhanov, A; Kozhakbayeva, M; Hoshi, M

    2015-09-01

    To explore the possibility to use the lens extract as an in vitro stimulator to conduct a test of stimulated leukergy in liquidators of the accident consequences (LAC) on Chernobyl Nuclear Power Plant (CNPP) with a cataract in the long-term period. The study sample included 72 men-LAC on CNPP, at the age from 42 to 65 y, who have a cataract. The comparison group consisted of 60 men, with a cataract, of the same age, and who were not exposed to radiation. The control group was composed of 60 men, at the age of 42-58 y without lens pathology. Phenomenon of the stimulated leukergy was revealed in persons who had been exposed to radiation in the dose of 18.2 ± 0.58 cGy and was observed in 5.7-8.05 % (P < 0.001), suggesting a continued high auto-aggression to the lens antigens, and the strength of cell-mediated immunity.

  19. Molecular Characterization of TP53 Gene in Human Populations Exposed to Low-Dose Ionizing Radiation

    PubMed Central

    Brasil-Costa, Igor; Alencar, Dayse O.; Raiol-Moraes, Milene; Pessoa, Igor A.; Brito, Alexandre W. M.; Jati, Schneyder R.; Santos, Sidney E. B.; Burbano, Rommel M. R.; Ribeiro-dos-Santos, Ândrea K. C.

    2013-01-01

    Ionizing radiation, such as that emitted by uranium, may cause mutations and consequently lead to neoplasia in human cells. The TP53 gene acts to maintain genomic integrity and constitutes an important biomarker of susceptibility. The present study investigated the main alterations observed in exons 4, 5, 6, 7, and 8 of the TP53 gene and adjacent introns in Amazonian populations exposed to radioactivity. Samples were collected from 163 individuals. Occurrence of the following alterations was observed: (i) a missense exchange in exon 4 (Arg72Pro); (ii) 2 synonymous exchanges, 1 in exon 5 (His179His), and another in exon 6 (Arg213Arg); (iii) 4 intronic exchanges, 3 in intron 7 (C → T at position 13.436; C → T at position 13.491; T → G at position 13.511) and 1 in intron 8 (T → G at position 13.958). Alteration of codon 72 was found to be an important risk factor for cancer development (P = 0.024; OR = 6.48; CI: 1.29–32.64) when adjusted for age and smoking. Thus, TP53 gene may be an important biomarker for carcinogenesis susceptibility in human populations exposed to ionizing radiation. PMID:23586029

  20. Deterministic effect of lens at leukergy of patients who received low doses of ionising radiation.

    PubMed

    Yeltokova, M; Zharliganova, D; Shaidarov, M; Bakhtin, M; Kazymbet, P; Tel, L; Dossakhanov, A; Kozhakbayeva, M; Hoshi, M

    2015-09-01

    To explore the possibility to use the lens extract as an in vitro stimulator to conduct a test of stimulated leukergy in liquidators of the accident consequences (LAC) on Chernobyl Nuclear Power Plant (CNPP) with a cataract in the long-term period. The study sample included 72 men-LAC on CNPP, at the age from 42 to 65 y, who have a cataract. The comparison group consisted of 60 men, with a cataract, of the same age, and who were not exposed to radiation. The control group was composed of 60 men, at the age of 42-58 y without lens pathology. Phenomenon of the stimulated leukergy was revealed in persons who had been exposed to radiation in the dose of 18.2 ± 0.58 cGy and was observed in 5.7-8.05 % (P < 0.001), suggesting a continued high auto-aggression to the lens antigens, and the strength of cell-mediated immunity. PMID:25969524

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

    SciTech Connect

    Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; Begriche, Karima; Trak-Smayra, Viviane; Martinais, Sophie; Porceddu, Mathieu; Robin, Marie-Anne; Fromenty, Bernard

    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

  2. Community Surveys: Low Dose Radiation. Fernald, Ohio and Rocky Flats, Colorado

    SciTech Connect

    C. K. Mertz; James Flynn; Donald G. MacGregor; Theresa Satterfield; Stephen M. Johnson; Seth Tuler; Thomas Webler

    2002-10-16

    This report is intended to present a basic description of the data from the two community surveys and to document the text of the questions; the methods used for the survey data collection; and a brief overview of the results. Completed surveys were conducted at local communities near the Rocky Flats, Colorado and the Fernald, Ohio sites; no survey was conducted for the Brookhaven, New York site. Fernald. The Fernald sample was randomly selected from 98% of all potential residential telephones in the townships of Ross, Morgan, and Crosby. The only telephone exchanges not used for the Fernald study had 4%, or fewer, of the holders of the telephone numbers actually living in either of the three target townships. Surveying started on July 24, 2001 and finished on August 30, 2001. A total of 399 completed interviews were obtained resulting in a CASRO response rate of 41.8%. The average length of an interview was 16.5 minutes. Rocky Flats. The sample was randomly selected from all potential residential telephones in Arvada and from 99% of the potential telephones in Westminster. Surveying started on August 10, 2001 and finished on September 25, 2001. A total of 401 completed interviews were obtained with a CASRO response rate of 32.5%. The average length of an interview was 15.7 minutes. Overall, respondents hold favorable views of science. They indicate an interest in developments in science and technology, feel that the world is better off because of science, and that science makes our lives healthier, easier, and more comfortable. However, respondents are divided on whether science should decide what is safe or not safe for themselves and their families. The majority of the respondents think that standards for exposure to radiation should be based on what science knows about health effects of radiation and on what is possible with today's technology. Although few respondents had visited the sites, most had heard or read something about Fernald or Rocky Flat s in the

  3. On application of low doses from beta radiation source in OSL retrospective dosimetry

    NASA Astrophysics Data System (ADS)

    Przegietka, K.; Chruscinska, A.

    2014-11-01

    The paper reports on three levels of dose rates obtainable from single beta source: (133±3) mGy/s, (17.8±0.3) mGy/s and (1.94±0.04) mGy/s, as calibrated for quartz sand grains. These values were achieved for different attenuation stages of beta radiation emitted by standard 90Sr/90Y source with the nominal activity of 1.48 GBq attached to an automatic luminescence reader. Lower dose rates give opportunity for exact dosing, which is especially required in luminescence dating applied to young samples as well as in environmental dosimetry. Moreover new method for determining time lag in opening the source in the Riso beta irradiator is presented. This allowed to resolve the contradiction appearing in the literature. The time delay was found to be (0.15±0.01) s per single irradiation. For improving accuracy the dose rate correction is suggest to be taken into account for irradiations shorter than 30 s.

  4. [Longevity of Drosophila after exposure to low doses of radiation and etoposide].

    PubMed

    Moskalev, A A; Zaĭnullin, V G

    2002-01-01

    The review of perennial researches of the authors on a problem of radiation-induced aging is presented. From the point of view of radiogenetics it is represented perspective to investigate influence of an exogenous irradiating in small doses on fruit fly with defined mutation by phenotypes, that allows to repute a role of separate genes and mechanisms, controlled by them, in a determination of lifetime. At lines described by differences in pattern of mobile genetical elements, the different reaction to an irradiating explained from the point of view of features of the given mobile elements is found. The processing etoposide in concentration 5 microM on preimaginal stages of line with defects of a reparation (mei-41D5) and hypersensibility to an induction apoptosis (wg1-7, wg7L74, th1 [symbol: see text] th4) results in down-stroke of lifetime. The dominant effect of a gene mei-41D5 in a regulation of etoposide-induced change of lifetime is found. Is exhibited, that at lines with defects proapoptosis of genes reaper and Dcp1, the lifetime after influence, both ionizing irradiating, and inducer apoptosis etoposide is enlarged in comparison with the control. PMID:12577692

  5. MPGD for breast cancer prevention: a high resolution and low dose radiation medical imaging

    NASA Astrophysics Data System (ADS)

    Gutierrez, R. M.; Cerquera, E. A.; Mañana, G.

    2012-07-01

    Early detection of small calcifications in mammograms is considered the best preventive tool of breast cancer. However, existing digital mammography with relatively low radiation skin exposure has limited accessibility and insufficient spatial resolution for small calcification detection. Micro Pattern Gaseous Detectors (MPGD) and associated technologies, increasingly provide new information useful to generate images of microscopic structures and make more accessible cutting edge technology for medical imaging and many other applications. In this work we foresee and develop an application for the new information provided by a MPGD camera in the form of highly controlled images with high dynamical resolution. We present a new Super Detail Image (S-DI) that efficiently profits of this new information provided by the MPGD camera to obtain very high spatial resolution images. Therefore, the method presented in this work shows that the MPGD camera with SD-I, can produce mammograms with the necessary spatial resolution to detect microcalcifications. It would substantially increase efficiency and accessibility of screening mammography to highly improve breast cancer prevention.

  6. Pathogen germs response to low-dose radiation — medical approach

    NASA Astrophysics Data System (ADS)

    Poiata, A.; Focea, R.; Creanga, D.

    2012-04-01

    The side effects of radiation therapy in the case of microbial loading of irradiated organs was considered as phenomenological basis of the experiment carried out on Staphylococcus aureus (ATCC germ) exposed to low X-ray doses. The inoculum was prepared in a liquid culture medium with standard composition, the volumes of 3 ml identical samples (in sterile glass tubes) being irradiated in hospital conditions. Five experimental variants were developed corresponding to irradiation time durations between 25 and 100 minutes. The spectro-colorimetric assay was accomplished at 560 nm and 420 nm, the resulting average values (for three repetitions) being analyzed from the viewpoint of cell density in the irradiated variants compared to control ones. The resistance to antibiotics of the irradiated bacteria was tested on agarized cultures against five antibiotic molecules (ampicillin, cloramphenicol, tetracycline, tobramicin and ofloxacin) by assessing the diameter of inhibition growth areas in each case. The increase of the inhibition area diameter with up to 15% (in the case of tetracycline) was noticed for the lowest irradiation time for all five antibiotics, which is suggesting a weakening of the bacteria resistance to the pharmaceutical agents following the X-ray treatment. This was concordant with the results of the spectro-colorimetric assay of the cell density within the directly irradiated bacteria cultures. The main issue of this study is concerning the optimization of the radiotherapy protocol in patients with potential microbial loading.

  7. Effect of exposure to low-dose [gamma] radiation during late organogenesis in the mouse fetus

    SciTech Connect

    Devi, P.U.; Baskar, R.; Hande, M.P. )

    1994-04-01

    The adominal region of pregnant Swiss mice was exposed to 0.05 to 0.50 of [gamma] radiation on day 11.5 postcoitus. The animals were sacrificed on day 18 gestation and the fetuses were examined for mortality, growth retardation, changes in head size and brain weight, and incidence of microphthalmia. No marked increase in fetal mortality or growth retardation was observed below 0.25 Gy; the increase in these parameters was significant only at 0.50 Gy. A significant reduction in head size and brain weight and a significant increase in the incidence of microphthalmia were observed at doses above 0.15 Gy. Detectable levels of microcephaly and microphthalmia were evident even at 0.10 Gy. A linear dose response was seen for these effects in the dose range of 0.05 to 0.15 Gy. It is concluded that the late period of organogenesis in the mouse, especially between days 10 and 12 postcoitus, is a particularly sensitive phase in the development of the skull, brain and eye. 21 refs., 4 figs., 4 tabs.

  8. Synaptotoxicity of chronic low-dose pre- and post-natal ethanol exposure: A new animal model

    SciTech Connect

    Walewski, J.L.

    1992-01-01

    Chronic Low-dose Pre- and Post-natal Ethanol exposure (CLPPEE) is the most frequent cause of teratogenically induced mental deficiency in the Western world. Although the Fetal Alcohol Syndrome (FAAS) is associated with high levels of alcohol consumption, the relative teratogenic risk of moderate ethanol consumption is not well defined. CLPPEE may affect some processes involved in synapse formation, affecting the proper development and maturation of the nervous system. Ethanol was admixed (3 v/v%) with high-protein liquid diet (Bio-Serve) as the only nutrient source. The controls received an isocaloric sucrose liquid diet mixture. Ethanol treatment began on day 8 of pregnancy. 3 v/v% ethanol did not significantly reduce the body weights or diet consumption of dams, nor the gross growth of ethanol-exposed pups. Standard neuromuscular twitch preparations in vivo, utilizing the sciatic nerve-gastrocnemius muscle, were done on 1, 2, 3 and 7 week old pups. The physiologic functional tests of nursing pups (1-3 weeks), indicated that the ethanol-treated pups had abnormal responses to indirect stimulation. The deficit was determined to be pre-synaptic. The ethanol-exposed at these ages demonstrated abnormal responses to presynaptic challenge. Histochemical staining revealed motor nerve terminal morphology. In 2 and 3 week ethanol-treated pups, the number of nerve terminal branches, and endplate lengths were significantly reduced. Reversibility was examined by allowing the pups to mature while receiving only standard rat chow and water. Tests were repeated at 7 weeks of age. The responses of the ethanol-exposed to pharmacologic challenge, and motor nerve terminal morphology were still significantly different in the young adult animals. CLPPEE, at doses sub-threshold for FAS, affects the normal development of the skeletal neuromuscular system, with long-lasting effects on motor nerve terminal function and morphology.

  9. Signal transduction through p53-dependent pathway after low-dose ionizing radiation

    SciTech Connect

    Ohnishi, T.; Matsumoto, H.; Wang Xinjiang

    1995-12-31

    In the study of cell-cycle events, recent attention has focused on the signal transduction pathway in which a tumor-suppressor protein, wild-type (wt) p53 protein, acts as the key protein. A major advance in recent years has been the partial elucidation of the G{sub 1}-arrest mechanism. However, the transcriptional regulation mechanisms of components of the cell-cycle machinery remain unknown. We have investigated the induction of p53, WAF1, and cdk2 after gamma-ray irradiation using two human glioblastoma cell lines, U-87MG bearing the wt p53 gene and the other, T98G, a mutant gene. After the cells have been irradiated with gamma rays at 3 Gy, the level of p53 and WAF1 mRNAs in U-87MG increased gradually for up to 10 h, whereas these mRNAs were overexpressed in T98G, and these levels remained relatively stable after irradiation. In an attempt to examine the induction of cdk2 after gamma-ray irradiation, we analyzed the level of cdk2 mRNA using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. We calculated the amounts of cdk2 mRNA relative to that of b-actin mRNA in both cell lines, then plotted them against those in nonirradiated cells. After irradiation, the level of cdk2 mRNA in U-87MG gradually increased more than twofold by 10 h after gamma-ray irradiation, whereas the level of the mRNA in T98G remained relatively stable after irradiation. This result demonstrates that wtp53 induces the expression of not only WAF1 but also cdk2. The induction of wt p53 protein accumulation in rats exposed to x radiation is also discussed.

  10. Coronary computed tomography angiography using ultra-low-dose contrast media: radiation dose and image quality.

    PubMed

    Komatsu, Sei; Kamata, Teruaki; Imai, Atsuko; Ohara, Tomoki; Takewa, Mitsuhiko; Ohe, Ryoko; Miyaji, Kazuaki; Yoshida, Junichi; Kodama, Kazuhisa

    2013-08-01

    To analyze the invasiveness and image quality of coronary CT angiography (CCTA) with 80 kV. We enrolled 181 patients with low body weight and low calcium level. Of these, 154 patients were randomly assigned to 1 of 3 groups: 280 HU/80 kV (n = 51); 350 HU/80 kV (n = 51); or 350 HU/120 kV (n = 52). The amount of contrast media (CM) was decided with a CT number-controlling system. Twenty-seven patients were excluded because of an invalid time density curve by timing bolus. The predicted amount of CM, volume CT dose index, dose-length product, effective dose, image noise, and 5-point image quality were measured. The amounts of CM for the 80 kV/280 HU, 80 kV/350 HU, and 120 kV/350 HU groups were 10 ± 4 mL, 15 ± 7 mL, and 30 ± 6 mL, respectively. Although image noise was greater at 80 than 120 kV, there was no significant difference in image quality between 80 kV/350 HU and 120 kV/350 HU (p = 0.390). There was no significant difference in image quality between 80 kV/280 HU and 80 kV/350 HU (4.4 ± 0.7 vs. 4.7 ± 0.4, p = 0.056). The amount of CM and effective dose was lower for 80 kV CCTA than for 120 kV CCTA. CCTA at 80 kV/280 HU may decrease the amount of CM and radiation dose necessary while maintaining image quality.

  11. Low-Dose Consolidation Radiation Therapy for Early Stage Unfavorable Hodgkin Lymphoma

    SciTech Connect

    Torok, Jordan A.; Wu, Yuan; Prosnitz, Leonard R.; Kim, Grace J.; Beaven, Anne W.; Diehl, Louis F.; Kelsey, Chris R.

    2015-05-01

    Purpose: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. Methods and Materials: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achieve a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. Results: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. Conclusions: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.

  12. In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation

    PubMed Central

    Barazzuol, Lara; Jeggo, Penny A.

    2016-01-01

    The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5–14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4Y288C), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4Y288C embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4Y288C mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis. PMID:27125639

  13. Low dose/low fluence ionizing radiation-induced biological effects: The role of intercellular communication and oxidative metabolism

    NASA Astrophysics Data System (ADS)

    Azzam, Edouard

    Mechanistic investigations have been considered critical to understanding the health risks of exposure to ionizing radiation. To gain greater insight in the biological effects of exposure to low dose/low fluence space radiations with different linear energy transfer (LET) properties, we examined short and long-term biological responses to energetic protons and high charge (Z) and high energy (E) ions (HZE particles) in human cells maintained in culture and in targeted and non-targeted tissues of irradiated rodents. Particular focus of the studies has been on mod-ulation of gene expression, proliferative capacity, induction of DNA damage and perturbations in oxidative metabolism. Exposure to mean doses of 1000 MeV/nucleon iron ions, by which a small to moderate proportion of cells in an exposed population is targeted through the nucleus by an HZE particle, induced stressful effects in the irradiated and non-irradiated cells in the population. Direct intercellular communication via gap-junctions was a primary mediator of the propagation of stressful effects from irradiated to non-irradiated cells. Compromised prolif-erative capacity, elevated level of DNA damage and oxidative stress evaluated by measurements of protein carbonylation, lipid peroxidation and activity of metabolic enzymes persisted in the progeny of irradiated and non-irradiated cells. In contrast, progeny of cells exposed to high or low doses from 150-1000 MeV protons retained the ability to form colonies and harbored similar levels of micronuclei, a surrogate form of DNA damage, as control, which correlated with normal reactive oxygen species (ROS) levels. Importantly, a significant increase in the spontaneous neoplastic transformation frequency was observed in progeny of bystander mouse embryo fibroblasts (MEFs) co-cultured with MEFs irradiated with energetic iron ions but not protons. Of particular significance, stressful effects were detected in non-targeted tissues of rats that received partial

  14. Enhancement of Peroxidase Release from Non-Malignant and Malignant Cells through Low-Dose Irradiation with Different Radiation Quality.

    PubMed

    Abdelrazzak, Abdelrazek B; Pottgießer, Stefanie J; Hill, Mark A; O'Neill, Peter; Bauer, Georg

    2016-02-01

    The release of peroxidase by nontransformed or transformed fibroblasts or epithelial cells (effector cells) triggers apoptosis induction selectively in transformed fibroblasts or transformed epithelial cells (target cells) through intercellular apoptosis-inducing signaling. The release of peroxidase can be induced either by treatment with transforming growth factor beta 1 or by low doses of alpha particles, gamma rays or ultrasoft X rays. In addiation, data indicates that radiation quality does not determine the overall efficiency of peroxidase release and the effects among a wide range of radiation doses are indistinguishable. These findings suggested that peroxidase release might be being triggered through intercellular bystander signaling. We show here that maximal peroxidase release does indeed occur after coculture of a small number of irradiated cells with an excess of unirradiated cells and demonstrate an enhanced effector function of nontransformed cells after the addition of a small number of irradiated cells. These data strongly indicate that peroxidase release is indeed triggered through bystander signaling mechanisms in mammalian cells.

  15. Single Low-Dose Radiation Induced Regulation of Keratinocyte Differentiation in Calcium-Induced HaCaT Cells

    PubMed Central

    Hahn, Hyung Jin; Youn, Hae Jeong; Cha, Hwa Jun; Kim, Karam; An, Sungkwan

    2016-01-01

    Background We are continually exposed to low-dose radiation (LDR) in the range 0.1 Gy from natural sources, medical devices, nuclear energy plants, and other industrial sources of ionizing radiation. There are three models for the biological mechanism of LDR: the linear no-threshold model, the hormetic model, and the threshold model. Objective We used keratinocytes as a model system to investigate the molecular genetic effects of LDR on epidermal cell differentiation. Methods To identify keratinocyte differentiation, we performed western blots using a specific antibody for involucrin, which is a precursor protein of the keratinocyte cornified envelope and a marker for keratinocyte terminal differentiation. We also performed quantitative polymerase chain reaction. We examined whether LDR induces changes in involucrin messenger RNA (mRNA) and protein levels in calcium-induced keratinocyte differentiation. Results Exposure of HaCaT cells to LDR (0.1 Gy) induced p21 expression. p21 is a key regulator that induces growth arrest and represses stemness, which accelerates keratinocyte differentiation. We correlated involucrin expression with keratinocyte differentiation, and examined the effects of LDR on involucrin levels and keratinocyte development. LDR significantly increased involucrin mRNA and protein levels during calcium-induced keratinocyte differentiation. Conclusion These studies provide new evidence for the biological role of LDR, and identify the potential to utilize LDR to regulate or induce keratinocyte differentiation. PMID:27489424

  16. Enhancement of Peroxidase Release from Non-Malignant and Malignant Cells through Low-Dose Irradiation with Different Radiation Quality.

    PubMed

    Abdelrazzak, Abdelrazek B; Pottgießer, Stefanie J; Hill, Mark A; O'Neill, Peter; Bauer, Georg

    2016-02-01

    The release of peroxidase by nontransformed or transformed fibroblasts or epithelial cells (effector cells) triggers apoptosis induction selectively in transformed fibroblasts or transformed epithelial cells (target cells) through intercellular apoptosis-inducing signaling. The release of peroxidase can be induced either by treatment with transforming growth factor beta 1 or by low doses of alpha particles, gamma rays or ultrasoft X rays. In addiation, data indicates that radiation quality does not determine the overall efficiency of peroxidase release and the effects among a wide range of radiation doses are indistinguishable. These findings suggested that peroxidase release might be being triggered through intercellular bystander signaling. We show here that maximal peroxidase release does indeed occur after coculture of a small number of irradiated cells with an excess of unirradiated cells and demonstrate an enhanced effector function of nontransformed cells after the addition of a small number of irradiated cells. These data strongly indicate that peroxidase release is indeed triggered through bystander signaling mechanisms in mammalian cells. PMID:26849404

  17. Reduced Ovarian Cancer Incidence in Women Exposed to Low Dose Ionizing Background Radiation or Radiation to the Ovaries after Treatment for Breast Cancer or Rectosigmoid Cancer

    PubMed Central

    Lehrer, Steven; Green, Sheryl; Rosenzweig, Kenneth E

    2016-01-01

    Background High dose ionizing radiation can induce ovarian cancer, but the effect of low dose radiation on the development of ovarian cancer has not been extensively studied. We evaluated the effect of low dose radiation and total background radiation, and the radiation delivered to the ovaries during the treatment of rectosigmoid cancer and breast cancer on ovarian cancer incidence. Materials and Methods Background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States, 2011. Ovarian cancer incidence data are from the Centers for Disease Control and Prevention. Standardized incidence ratios (SIR) of ovarian cancer following breast cancer and rectosigmoid cancer are from Surveillance, Epidemiology, and End Results (SEER) data. Obesity data by US state are from the Centers for Disease Control and Prevention. Mean ages of US state populations are from the United States Census Bureau. Results We calculated standardized incidence ratios (SIR) from Surveillance, Epidemiology, and End Results (SEER) data, which reveal that in 194,042 cases of breast cancer treated with beam radiation, there were 796 cases of ovarian cancer by 120+ months of treatment (0.41%); in 283, 875 cases of breast cancer not treated with radiation, there were 1,531 cases of ovarian cancer by 120+ months (0.54%). The difference in ovarian cancer incidence in the two groups was significant (p < 0.001, two tailed Fisher exact test). The small dose of scattered ovarian radiation (about 3.09 cGy) from beam radiation to the breast appears to have reduced the risk of ovarian cancer by 24%. In 13,099 cases of rectal or rectosigmoid junction cancer treated with beam radiation in the SEER data, there were 20 cases of ovarian cancer by 120+ months of treatment (0.15%). In 33,305 cases of rectal or rectosigmoid junction cancer not treated with radiation, there were 91 cases of ovarian cancer by 120+ months (0.27%). The difference in ovarian cancer incidence in the

  18. Mechanisms and biological importance of photon-induced bystander responses: do they have an impact on low-dose radiation responses.

    PubMed

    Tomita, Masanori; Maeda, Munetoshi

    2015-03-01

    Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect.

  19. Long-Term Effects of Low-Dose Spironolactone on Chronic Dialysis Patients: A Randomized Placebo-Controlled Study.

    PubMed

    Lin, ChongTing; Zhang, Qing; Zhang, HuiFang; Lin, AiXia

    2016-02-01

    The purpose of this 2-year multicentric, randomized, placebo-controlled study was to evaluate the long-term effects and adverse effects of spironolactone on chronic dialysis patients. A total of 253 non-heart failure dialysis patients with end-stage renal disease were randomly assigned to 2-year treatment with spironolactone (25 mg once daily, n=125) or a matching placebo (n=128) as add-on therapy. The primary outcome was a composite of death from cardiocerebrovascular (CCV) events, aborted cardiac arrest, and sudden cardiac death, and the secondary outcome was death from all causes. Other CCV-related indexes such as left ventricular mass index, left ventricular ejection fraction, heart rate variability, vascular endothelial function, and blood pressure-lowering effect were analyzed for patients who completed the whole 2-year follow-up study. Sociodemographic, clinical, and relevant laboratory data were also collected. During the 2-year follow-up, the primary outcome occurred less frequently in the spironolactone group vs the control group (7.2% vs 18.0%; adjusted hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.26-0.78). Death from CCV events occurred in 4.0% of patients in the spironolactone group and in 11.7% of patients in the control group. Neither aborted cardiac arrest nor sudden cardiac death was significantly reduced by spironolactone treatment. The secondary outcome occurred less frequently in the spironolactone group vs the control group (9.6% vs 19.5%; adjusted HR, 0.52; 95% CI, 0.29-0.94). Other CCV-related indexes except for heart rate variability were significantly improved. This study demonstrates that use of low-dose spironolactone in non-heart failure dialysis patients can effectively reduce the risks of both CCV morbidity and mortality with few side effects. Moreover, the beneficial effect was mediated through improving the endothelial function or reducing left ventricular size independent of blood pressure changes, rather than mediation

  20. The acceleration of amygdala kindling epileptogenesis by chronic low-dose corticosterone involves both mineralocorticoid and glucocorticoid receptors.

    PubMed

    Kumar, Gaurav; Couper, Abbie; O'Brien, Terence J; Salzberg, Michael R; Jones, Nigel C; Rees, Sandra M; Morris, Margaret J

    2007-08-01

    We have previously demonstrated that low-dose corticosterone (CS) administration, used as a model of the effect of chronic stress, accelerates epileptogenesis in the electrical amygdala kindling rat model of temporal lobe epilepsy (TLE). This current study examined the relative contributions to this effect of mineralocorticoid (MR) and glucocorticoid (GR) subtypes of glucocorticoid receptors. Female non-epileptic wistar rats 10-13 weeks of age were implanted with a bipolar electrode into the left amygdala. Five treatment groups were subjected to rapid amygdala kindling: water-control (n=9), CS treated (6 mg/100 ml added to drinking water; n=9), CS+spironolactone (MR antagonist, 50 mg/kg sc; n=9), CS+mifepristone (GR antagonist, 25 mg/kg sc; n=9), and CS+both antagonists (n=7). Rats were injected with vehicle or the relevant antagonist twice daily for the entire kindling period. Experimental groups differed significantly in the number of stimulations required to reach the 'fully kindled state' (Racine, 1972) ANOVA, F(4,38)=2.73, p=0.04). Amygdala kindling was accelerated in the CS-treated group compared with water controls (mean stimulations for full kindling: 45.2 vs. 86.5, p<0.01). This acceleration was inhibited by both the MR and GR antagonist treatments (mean stimulations: 69.6 and 70.4, p=0.04 and 0.04 vs. CS group, respectively), with the kindling rates in these groups not significantly different from water-treated subjects (p=0.26 and 0.29, respectively). The kindling rates in the MR and GR antagonist treatment groups did not significantly differ from each other (p=0.93), nor from the combined treatment group (mean stimulations: 62.8, p=0.59 and 0.54, respectively). This study demonstrates that activation of both high-affinity (MR) and low-affinity (GR) glucocorticoid receptors are involved in mediating CS-induced acceleration of amygdala kindling epileptogenesis.

  1. [Current epidemiological evidence regarding the health effects of low-dose ionizing radiation. Implications for radiation protection, public health and forensic medicine].

    PubMed

    Manzoli, Lamberto; Romano, Ferdinando; Schioppa, Francesco; D'Ovidio, Cristian; Lodi, Vittorio; Pirone, Giovanni Maria

    2004-01-01

    The health effects of low-dose ionizing radiation have been widely studied, but remain uncertain. Up-to-date knowledge about epidemiologic evidence for potential human health effects of low dose ionizing radiation is important for revising national radiation protection legislation. This review, conducted by a multidisciplinary research team of the Italian Institute of Social Medicine, evaluates epidemiologic studies published since July 2003. After careful selection, a total of 302 studies were reviewed. Greater emphasis was given to papers that analyzed data using standardized incidence and mortality ratios and to studies regarding occupational exposures in all workers, healthcare workers and aircrew members. Nevertheless, studies regarding A-bomb survivors of Hiroshima/Nagasaki, Chernobyl cleanup workers, patients exposed for medical reasons, and workers in nuclear plants were also included. Given the limitations of epidemiological studies and excluding the cosmic rays context, which requires further research, the authors conclude that harmful effects from exposures to ionizing radiation at doses lower than 100 mSv cannot be ruled out. Nevertheless, if any harmful health effects do exist, they are certainly very small. The implications for radiation protection, public health and forensic medicine are discussed. PMID:15213763

  2. Corticosterone protects against memory impairments and reduced hippocampal BDNF levels induced by a chronic low dose of ethanol in C57BL/6J mice.

    PubMed

    Ebada, Mohamed Elsaed; Latif, Liaque M; Kendall, David A; Pardon, Marie Christine

    2014-01-01

    Acute low doses of ethanol can produce reversible memory deficits, but it is unknown whether they persist upon chronic use. We investigated whether the chronic intake of a low dose of ethanol induces memory impairments in the ethanol-preferring C57BL/6J mouse strain. Because stress precipitates alcohol abuse and the stress hormone corticosterone contributes to memory processes, ethanol consumption and toxic effects, we also determined the impact of co-treatment with corticosterone on these effects. BDNF contributes to memory function and toxic effects of ethanol, therefore its levels were quantified in the hippocampus and frontal cortex. Ethanol (1% in drinking water) and corticosterone (250 μg/mL) were administered using the two-bottle choice test to monitor their appetitive properties. Spatial and non-spatial memory performance was assessed using the spontaneous alternation, object recognition and object location tests. The chronic exposure to a low dose of ethanol caused spatial and non-spatial memory deficits after withdrawal associated with a reduction in hippocampal BDNF levels, which were prevented by co-treatment with corticosterone (~21 mg/kg/day). The protective effect of corticosterone on memory was no longer observed at higher doses (~41 mg/kg/day), but persisted for hippocampal BDNF levels. C57BL/6J mice did not develop an appetence for 1% ethanol, but the addition of corticosterone increased voluntary consumption of and preference for the ethanol+corticosterone solutions. Although acute low doses of corticosterone (1 mg/kg) were found to rescue established memory impairments, this is the first report of a protective effect of chronic doses of corticosterone in the range of 20-32 mg/kg, and particularly against memory deficits induced by alcohol. PMID:25611260

  3. Low-Dose Involved-Field Radiation in the Treatment of Non-Hodgkin Lymphoma: Predictors of Response and Treatment Failure

    SciTech Connect

    Russo, Andrea L.; Chen, Yu-Hui; Martin, Neil E.; Vinjamoori, Anant; Luthy, Sarah K.; Freedman, Arnold; Michaelson, Evan M.; Silver, Barbara; Mauch, Peter M.; Ng, Andrea K.

    2013-05-01

    Purpose: To investigate clinical and pathologic factors significant in predicting local response and time to further treatment after low-dose involved-field radiation therapy (LD-IFRT) for non-Hodgkin lymphoma (NHL). Methods and Materials: Records of NHL patients treated at a single institution between April 2004 and September 2011 were retrospectively reviewed. Low-dose involved-field radiation therapy was given as 4 Gy in 2 fractions over 2 consecutive days. Treatment response and disease control were determined by radiographic studies and/or physical examination. A generalized estimating equation model was used to assess the effect of tumor and patient characteristics on disease response. A Cox proportional hazards regression model was used to assess time to further treatment. Results: We treated a total of 187 sites in 127 patients with LD-IFRT. Histologies included 66% follicular, 9% chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, 10% marginal zone, 6% mantle cell lymphoma (MCL), and 8% other. Median follow-up time was 23.4 months (range, 0.03-92.2 months). The complete response, partial response, and overall response rates were 57%, 25%, and 82%, respectively. A CLL histology was associated with a lower response rate (odds ratio 0.2, 95% confidence interval 0.1-0.5, P=.02). Tumor size, site, age at diagnosis, and prior systemic therapy were not associated with response. The median time to first recurrence was 13.6 months. Those with CLL and age ≤50 years at diagnosis had a shorter time to further treatment for local failures (hazard ratio [HR] 3.63, P=.01 and HR 5.50, P=.02, respectively). Those with CLL and MCL had a shorter time to further treatment for distant failures (HR 11.1 and 16.3, respectively, P<.0001). Conclusions: High local response rates were achieved with LD-IFRT across most histologies. Chronic lymphocytic leukemia and MCL histologies and age ≤50 years at diagnosis had a shorter time to further treatment after LD-IFRT.

  4. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated With Low-Dose-Rate Brachytherapy

    SciTech Connect

    Ho, Alice Y.; Burri, Ryan J.; Cesaretti, Jamie A.; Stone, Nelson N.; Stock, Richard G.

    2009-09-01

    Purpose: To evaluate the influence of patient- and treatment-related factors on freedom from biochemical failure (FFbF) in patients with intermediate-risk prostate cancer. Methods and Materials: From a prospectively collected database of 2250 men treated at Mount Sinai Hospital from 1990 to 2004 with low-dose-rate brachytherapy for prostate cancer, 558 men with either one or more intermediate-risk features (prostate-specific antigen [PSA] level 10-20 ng/mL, Gleason score 7, or Stage T2b) were identified who had a minimum follow-up of 24 months and postimplant CT-based dosimetric analysis. Biologically effective dose (BED) values were calculated to compare doses from different isotopes and treatment regimens. Patients were treated with brachytherapy with or without hormone therapy and/or external-beam radiotherapy. Patient- and treatment-related factors were analyzed with respect to FFbF. The median follow-up was 60 months (range, 24-167 months). Biochemical failure was defined according to the Phoenix definition. Univariate analyses were used to determine whether any variable was predictive of FFbF. A two-sided p value of <0.05 was considered significant. Results: Overall, the actuarial FFbF at 10 years was 86%. Dose (BED <150 Gy{sub 2} vs. {>=}150 Gy{sub 2}) was the only significant predictor of FFbF (p < 0.001). None of the other variables (PSA, external-beam radiotherapy, Gleason score, treatment type, hormones, stage, and number of risk factors) was found to be a statistically significant predictor of 10-year FFbF. Conclusions: Radiation dose is an important predictor of FFbF in intermediate-risk prostate cancer. Treatment should continue to be individualized according to presenting disease characteristics until results from Radiation Therapy Oncology Group trial 0232 become available.

  5. Is the Linear No-Threshold Dose-Response Paradigm Still Necessary for the Assessment of Health Effects of Low Dose Radiation?

    PubMed

    Seong, Ki Moon; Seo, Songwon; Lee, Dalnim; Kim, Min-Jeong; Lee, Seung-Sook; Park, Sunhoo; Jin, Young Woo

    2016-02-01

    Inevitable human exposure to ionizing radiation from man-made sources has been increased with the proceeding of human civilization and consequently public concerns focus on the possible risk to human health. Moreover, Fukushima nuclear power plant accidents after the 2011 East-Japan earthquake and tsunami has brought the great fear and anxiety for the exposure of radiation at low levels, even much lower levels similar to natural background. Health effects of low dose radiation less than 100 mSv have been debated whether they are beneficial or detrimental because sample sizes were not large enough to allow epidemiological detection of excess effects and there was lack of consistency among the available experimental data. We have reviewed an extensive literature on the low dose radiation effects in both radiation biology and epidemiology, and highlighted some of the controversies therein. This article could provide a reasonable view of utilizing radiation for human life and responding to the public questions about radiation risk. In addition, it suggests the necessity of integrated studies of radiobiology and epidemiology at the national level in order to collect more systematic and profound information about health effects of low dose radiation. PMID:26908982

  6. Is the Linear No-Threshold Dose-Response Paradigm Still Necessary for the Assessment of Health Effects of Low Dose Radiation?

    PubMed Central

    2016-01-01

    Inevitable human exposure to ionizing radiation from man-made sources has been increased with the proceeding of human civilization and consequently public concerns focus on the possible risk to human health. Moreover, Fukushima nuclear power plant accidents after the 2011 East-Japan earthquake and tsunami has brought the great fear and anxiety for the exposure of radiation at low levels, even much lower levels similar to natural background. Health effects of low dose radiation less than 100 mSv have been debated whether they are beneficial or detrimental because sample sizes were not large enough to allow epidemiological detection of excess effects and there was lack of consistency among the available experimental data. We have reviewed an extensive literature on the low dose radiation effects in both radiation biology and epidemiology, and highlighted some of the controversies therein. This article could provide a reasonable view of utilizing radiation for human life and responding to the public questions about radiation risk. In addition, it suggests the necessity of integrated studies of radiobiology and epidemiology at the national level in order to collect more systematic and profound information about health effects of low dose radiation. PMID:26908982

  7. A functional genomics approach using radiation-induced changes in gene expression to study low dose radiation effects in vitro and in vivo

    SciTech Connect

    Fornace, Jr, A J

    2007-03-03

    Abstract for final report for project entitled A functional genomics approach using radiation-induced changes in gene expression to study low dose radiation effects in vitro and in vivo which has been supported by the DOE Low Dose Radiation Research Program for approximately 7 years. This project has encompassed two sequential awards, ER62683 and then ER63308, in the Gene Response Section in the Center for Cancer Research at the National Cancer Institute. The project was temporarily suspended during the relocation of the Principal Investigators laboratory to the Dept. of Genetics and Complex Diseases at Harvard School of Public Health at the end of 2004. Remaining support for the final year was transferred to this new site later in 2005 and was assigned the DOE Award Number ER64065. The major aims of this project have been 1) to characterize changes in gene expression in response to low-dose radiation responses; this includes responses in human cells lines, peripheral blood lymphocytes (PBL), and in vivo after human or murine exposures, as well as the effect of dose-rate on gene responses; 2) to characterize changes in gene expression that may be involved in bystander effects, such as may be mediated by cytokines and other intercellular signaling proteins; and 3) to characterize responses in transgenic mouse models with relevance to genomic stability. A variety of approaches have been used to study transcriptional events including microarray hybridization, quantitative single-probe hybridization which was developed in this laboratory, quantitative RT-PCR, and promoter microarray analysis using genomic regulatory motifs. Considering the frequent responsiveness of genes encoding cytokines and related signaling proteins that can affect cellular metabolism, initial efforts were initiated to study radiation responses at the metabolomic level and to correlate with radiation-responsive gene expression. Productivity includes twenty-four published and in press manuscripts

  8. Intensity-modulated radiation therapy for pancreatic and prostate cancer using pulsed low-dose rate delivery techniques.

    PubMed

    Li, Jie; Lang, Jinyi; Wang, Pei; Kang, Shengwei; Lin, Mu-Han; Chen, Xiaoming; Chen, Fu; Guo, Ming; Chen, Lili; Ma, Chang-Ming Charlie

    2014-01-01

    Reirradiation of patients who were previously treated with radiotherapy is vastly challenging. Pulsed low-dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while providing significant tumor control for recurrent cancers. This work investigates treatment planning techniques for intensity-modulated radiation therapy (IMRT)-based PLDR treatment of various sites, including cases with pancreatic and prostate cancer. A total of 20 patients with clinical recurrence were selected for this study, including 10 cases with pancreatic cancer and 10 with prostate cancer. Large variations in the target volume were included to test the ability of IMRT using the existing treatment planning system and optimization algorithm to deliver uniform doses in individual gantry angles/fields for PLDR treatments. Treatment plans were generated with 10 gantry angles using the step-and-shoot IMRT delivery technique, which can be delivered in 3-minute intervals to achieve an effective low dose rate of 6.7cGy/min. Instead of dose constraints on critical structures, ring structures were mainly used in PLDR-IMRT optimization. In this study, the PLDR-IMRT plans were compared with the PLDR-3-dimensional conformal radiation therapy (3DCRT) plans and the PLDR-RapidArc plans. For the 10 cases with pancreatic cancer that were investigated, the mean planning target volume (PTV) dose for each gantry angle in the PLDR-IMRT plans ranged from 17.6 to 22.4cGy. The maximum doses ranged between 22.9 and 34.8cGy. The minimum doses ranged from 8.2 to 17.5cGy. For the 10 cases with prostate cancer that were investigated, the mean PTV doses for individual gantry angles ranged from 18.8 to 22.6cGy. The maximum doses per gantry angle were between 24.0 and 34.7cGy. The minimum doses per gantry angle ranged from 4.4 to 17.4cGy. A significant reduction in the organ at risk (OAR) dose was observed with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. The

  9. Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats.

    PubMed

    Samantaray, Supriti; Das, Arabinda; Matzelle, Denise C; Yu, Shan P; Wei, Ling; Varma, Abhay; Ray, Swapan K; Banik, Naren L

    2016-05-01

    Spinal cord injury (SCI) causes loss of neurological function and, depending upon the severity of injury, may lead to paralysis. Currently, no FDA-approved pharmacotherapy is available for SCI. High-dose methylprednisolone is widely used, but this treatment is controversial. We have previously shown that low doses of estrogen reduces inflammation, attenuates cell death, and protects axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of this study was to investigate whether low doses of estrogen in post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40 g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 μg 17β-estradiol (estrogen) for 7 days following SCI and compared with vehicle-treated injury and laminectomy (sham) controls. Histology (H&E staining), immunohistofluorescence, Doppler laser technique, and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, the expression of angiogenic factors, axonal degeneration, and locomotor function (Basso, Beattie, and Bresnahan rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42 days post injury. A reduction in glial reactivity, attenuation of axonal and myelin damage, protection of cells, increased expression of angiogenic factors and microvessel growth, and improved locomotor function were found following estrogen treatment compared with vehicle-treated SCI rats. These results suggest that treatment with a very low dose of estrogen has significant therapeutic implications for the improvement of locomotor function in chronic SCI. Experimental studies with low dose estrogen therapy in chronic spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes that could ameliorate the degenerative pathways in chronic SCI as

  10. Curcumin and epithelial-mesenchymal transition in breast cancer cells transformed by low doses of radiation and estrogen.

    PubMed

    Gallardo, Marcela; Calaf, Gloria M

    2016-06-01

    Breast cancer is a major cause of global mortality in women. Curcumin exerts anti-proliferative, anti-migratory and apoptotic effects. The aim of this study was to evaluate gene expression involved in epithelial-mesenchymal transition (EMT). An in vitro model was developed with the MCF-10F immortalized breast epithelial cell line exposed to low radiation doses of high LET (linear energy transfer) α-particles (150 keV/µm) and cultured in the presence of 17β-estradiol (estrogen). The following cell lines were used: i) MCF-10F, normal; ii) Alpha5, pre-tumorigenic, and iii) Tumor2 derived from Alpha5 injected into the nude mice. Our previous results have shown that Alpha5 and Tumor2 increased cell proliferation, anchorage independency, invasive capabilities and tumor formation in nude mice in comparison to control. Results indicated that curcumin decreased expression of EMT-related genes in Tumor2 cell line when compared to its counterpart as E-cadherin, N-cadherin, ZEB2, Twist1, Slug, Axl, vimentin, STAT-3, fibronectin; and genes p53 and caveolin-1, as well as apoptotic genes caspase-3, caspase-8, and others such as cyclin D1 and NFκB. All these changes induced a decrease in migratory and invasive capabilities of such a cell line. Thus, it seems that curcumin may impinge upon apoptosis and metastatic properties of the malignant cells exerting antitumor activity in breast cancer cells transformed by low doses of α-particles and estrogen in vitro. PMID:27082017

  11. Modeling cell response to low doses of photon irradiation: Part 2--application to radiation-induced chromosomal aberrations in human carcinoma cells.

    PubMed

    Cunha, Micaela; Testa, Etienne; Komova, Olga V; Nasonova, Elena A; Mel'nikova, Larisa A; Shmakova, Nina L; Beuve, Michaël

    2016-03-01

    The biological phenomena observed at low doses of ionizing radiation (adaptive response, bystander effects, genomic instability, etc.) are still not well understood. While at high irradiation doses, cellular death may be directly linked to DNA damage, at low doses, other cellular structures may be involved in what are known as non-(DNA)-targeted effects. Mitochondria, in particular, may play a crucial role through their participation in a signaling network involving oxygen/nitrogen radical species. According to the size of the implicated organelles, the fluctuations in the energy deposited into these target structures may impact considerably the response of cells to low doses of ionizing irradiation. Based on a recent simulation of these fluctuations, a theoretical framework was established to have further insight into cell responses to low doses of photon irradiation, namely the triggering of radioresistance mechanisms by energy deposition into specific targets. Three versions of a model are considered depending on the target size and on the number of targets that need to be activated by energy deposition to trigger radioresistance mechanisms. These model versions are applied to the fraction of radiation-induced chromosomal aberrations measured at low doses in human carcinoma cells (CAL51). For this cell line, it was found in the present study that the mechanisms of radioresistance could not be triggered by the activation of a single small target (nanometric size, 100 nm), but could instead be triggered by the activation of a large target (micrometric, 10 μm) or by the activation of a great number of small targets. The mitochondria network, viewed either as a large target or as a set of small units, might be concerned by these low-dose effects. PMID:26708100

  12. [Mechanism of injury of air-dry pea seeds under the influence of low doses of gamma-radiation].

    PubMed

    Veselova, T V; Veselovskiĭ, V A

    2012-01-01

    The aim of this work was to determine which processes in air-dry seeds result in bimodal changes of the pea seed quality under the influence of low doses of gamma-radiation. Pea seeds (cv. "Nemchinovsky-85", harvest 2006, 82% germination persentage) were exposed to gamma-radiation at doses of 3, 10 and 100 Gy The germination percentage decreased to 45% four days after irradiation at the dose of 3 Gy, rised up to 87% at doses of 10 Gy, while the dose of 100 Gy killed the most part of seeds. Seed fractions differing in quality were selected using the metod of Room temperature phosphorecsence (RTP): strong seed frasction I from non-irradiated seeds; weak seed fraction II from the seeds irradiated at a dose of 3 Gy; dead seeds from the seeds irradiated at a dose of 100 Gy. ThermoChemiLuminecnsece (TCL) of seed powders and cotyledons was used. It was shown that the increase of the TCL level in the temperature range from 50 to 110 degreesC was associated with the lipid peroxidation products. The TCL level of seeds subjected to gamma-irradiation at a dose of 3 Gy was similar to that of non-irradiated seeds in the temperature range 50 to 100 degreesC. Therefore, lipid peroxidation was not the cause of the abnormal seedling appearance. The TCL level within this temperature range was increased only in seeds subjected to y-irradiation at a dose of 100 Gy. The TCL level at 150 degreesC was in proportion with the exogenous glucose amount. The increased TCL level of seeds subjected to y-irradiation at a dose of 3 Gy at 150 degreesC resulted from the increase of the glucose content. This means that the transition from the fraction of strong seeds into the fraction of weak ones was the result of the activation of hydrolysis processes. Decrease in the water content of seeds testified to utilization of bound water in this process. The decrease of the glucose content in the "improved" seeds subjected to gamma-irradiation at a dose of 10 Gy most probably indicates the participation of

  13. Non-Target Effect for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Doses of High LET Radiation

    NASA Technical Reports Server (NTRS)

    Hada, Megumi; George, Kerry A.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (.01 - 0.2 Gy) of 170 MeV/u Si-28-ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The curves for doses above 0.1 Gy were more than one ion traverses a cell showed linear dose responses. However, for doses less than 0.1 Gy, Si-28-ions showed no dose response, suggesting a non-targeted effect when less than one ion traversal occurs. Additional findings for Fe-56 will be discussed.

  14. Cancer risk from low dose radiation depends directly on the organ mass in a general model of radiation-induced cancer risk.

    PubMed

    Lin, Z W

    2014-04-01

    Current methods of evaluating radiation-induced cancer risk depend on the organ dose but not explicitly on extensive quantities such as the organ mass. However, at the same organ dose, one may expect the larger number of cells in a larger organ to lead to a higher cancer risk. Here the author introduces organ- and radiation type-specific cell cancer risk coefficients and obtains analytical relations between cancer risk and the radiation environment, which contains the dependence of cancer risk on organ masses. The excess cancer risk induced by low dose radiation for an organ is shown to be directly proportional to the organ mass. Therefore the total excess risk for all solid cancers depends directly on organ masses and consequently on body weight or size. This method is also being compared with three existing methods of evaluating the radiation-induced cancer risk, and special cases where this formulation matches each method are demonstrated. The results suggest that the direct dependence of cancer risk on organ masses needs to be checked against existing epidemiological data and, if verified, should be included in the methodology for the evaluation of radiation-induced cancer risk, in particular the individual risk. This dependence is also expected to affect the cancer risk transport from one population group to another that is different in organ mass, body weight or height. PMID:24562066

  15. Possibilities and limitations of fluorescence in situ hybridization technique in retrospective detection of low dose radiation exposure in post-chernobyl human cohorts.

    PubMed

    Maznyk, N A; Vinnikov, V A

    2005-01-01

    Cytogenetic analysis using the fluorescence in situ hybridisation (FISH) technique was performed late time after the Chernobyl accident in groups of liquidators, evacuees from 30 km exclusive zone, residents of radioactively contaminated areas and control donors age-matched to exposed persons. Stable and unstable chromosome type exchanges were recorded using a hybrid conventional-PAINT nomenclature. The mean yield of stable chromosome exchanges in liquidators did not correlate with registered radiation doses but had a clear negative dependence on the duration of liquidators' staying in Chernobyl zone, that was in a good agreement with early data based on conventional dicentrics plus rings analysis. The overspontaneous excess for stable chromosome exchange level appeared to be higher in evacuees 16-40 years old than that of senior persons, whereas no age-dependent difference occurred for initially induced dicentrics plus rings yields in this cohort. The stable chromosome exchange yield, as well as combined yield of dicentrics plus rings and potentially unstable incomplete translocations in residents of radioactively contaminated areas showed a reasonable positive correlation with levels of 137Cs contamination. The observed yields of stable chromosome exchanges in all three exposed groups appeared to be somewhat lower than those of expected from unstable exchange-based doses which were referred to an in vitro dose response of stable exchanges outcome in human lymphocytes. Thus, FISH analysis can be successfully applied for qualitative cytogenetic indication of past and chronic radiation exposure to low doses but further refinement of FISH-based system for quantitative dose assessment is still required. Some practical approaches of solving this task are discussed.

  16. Carcinogenesis From Inhaled (PuO2)-Pu-239 in Beagles: Evidence for Radiation Homeostasis at Low Doses?

    SciTech Connect

    Fisher, Darrell R.; Weller, Richard E.

    2010-09-01

    Gy), and only one lung tumor was observed in 10 dogs with lung doses ranging from 27 to 48 cGy (mean 37.5 ± 10.9 cGy). By least-squares analysis, a quadratic function represented the overall dose-response (n = 137, r = 0.96) with no dose threshold. Reducing this function to three linear dose-response components, risk coefficients were calculated for each. The incidence of lung tumors at zero dose was significantly greater than the incidence at low dose (at the p ≤ 0.053 confidence level), suggesting a protective effect (radiation homeostasis) of alpha-particle radiation from 239PuO2. If a threshold for lung cancer incidence exists, it will be observed in the range 15 to 40 cGy.

  17. Dosimetry for quantitative analysis of the effects of low-dose ionizing radiation in radiation therapy patients.

    PubMed

    Lehmann, Joerg; Stern, Robin L; Daly, Thomas P; Rocke, David M; Schwietert, Chad W; Jones, Gregory E; Arnold, Michelle L; Siantar, Christine L Hartmann; Goldberg, Zelanna

    2006-02-01

    We have developed and validated a practical approach to identifying the location on the skin surface that will receive a prespecified biopsy dose (ranging down to 1 cGy) in support of in vivo biological dosimetry in humans. This represents a significant technical challenge since the sites lie on the patient's surface outside the radiation fields. The PEREGRINE Monte Carlo simulation system was used to model radiation dose delivery, and TLDs were used for validation on phantoms and for confirmation during patient treatment. In the developmental studies, the Monte Carlo simulations consistently underestimated the dose at the biopsy site by approximately 15% (of the local dose) for a realistic treatment configuration, most likely due to lack of detail in the simulation of the linear accelerator outside the main beam line. Using a single, thickness-independent correction factor for the clinical calculations, the average of 36 measurements for the predicted 1-cGy point was 0.985 cGy (standard deviation: 0.110 cGy) despite patient breathing motion and other real-world challenges. Since the 10-cGy point is situated in the region of high-dose gradient at the edge of the field, patient motion had a greater effect, and the six measured points averaged 5.90 cGy (standard deviation: 1.01 cGy), a difference that is equivalent to approximately a 6-mm shift on the patient's surface. PMID:16435922

  18. Effect of low-dose (1 kGy) gamma radiation and selected phosphates on the microflora of vacuum-packaged ground pork

    SciTech Connect

    Ehioba, R.M.

    1987-01-01

    The effects of low-dose (1 kGy) gamma radiation and selected phosphates on the microbiology of refrigerated, vacuum-packaged ground pork were studied. Low-dose gamma radiation reduced the numbers of naturally occurring mesophiles, psychrotrophs, and anaerobes. The effect of low-dose radiation on the populations of lactic acid bacteria was minimal. On storage of the irradiated vacuum-packaged ground pork at 5/sup 0/C, there was a partial bacterial recovery, suggesting sublethal bacterial injury due to irradiation. When 10/sup 7/ CFU/g of meat is taken to be the level beyond which the meat would be considered spoiled, uninoculated, vacuum-packaged ground pork treated with 1 kGy (100 krad) of gamma radiation had 3.5 more days of shelf-life in terms of psychrotrophic total counts. In relation to anaerobic bacterial numbers, meat shelf-life was extended 2.5 days, while the shelf-life of meat was extended 1 day in terms of aerobic mesophilic bacteria. Irradiation prolonged shelf-life in inoculated (10/sup 5/CFU/g) meat for 1.0-1.5 days. Addition of 0.4% sodium acid pyrophosphate (SAPP) contributed 2 additional days to inoculated, irradiated vacuum-packaged ground pork shelf-life. However, SAPP had no added effect on naturally occurring microflora. Irradiation greatly decreased the numbers of gram-negative microorganisms, resulting in predominance of the gram-positive, nonsporeforming Lactobacillus and coryneform bacteria.

  19. Low Dose Risk, Decisions, and Risk Communication

    SciTech Connect

    Flynn, James

    2002-09-14

    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.

  20. [Effect of prolonged administration of low doses of essential oils on the immune response and sensitivity of mice to the action of ionizing radiation].

    PubMed

    Isaeva, V G; Alinkina, E S; Misharina, T A; Fatkullina, L D; Dukhova, N N; Surinov, B P; Burlakova, E B

    2014-01-01

    The effect of ionizing radiation (1 Gy) on the immunological characteristics of spleen in the mice that consumed essential oils of oregano, clove bud and the mixture of lemon oil with ginger extract at low doses with drinking water for 6 months was studied. It was found that the essential oils increased the content of antibody forming lymphocyte cells in the spleen. The maximal effect in comparison with control was found for essential oil of clove bud. PMID:25764843

  1. Efficacy and tolerability of low-dose oral prolonged-release oxycodone/naloxone for chronic nononcological pain in older patients

    PubMed Central

    Guerriero, Fabio; Sgarlata, Carmelo; Marcassa, Claudio; Ricevuti, Giovanni; Rollone, Marco

    2015-01-01

    Purpose Chronic pain is highly prevalent in older adults. Increasing evidence indicates strong opioids as a valid option for chronic pain management in geriatrics. The aim of this study was to evaluate efficacy and safety of low-dose oral prolonged-release oxycodone–naloxone (OXN-PR) in patients aged ≥70 years. Methods This open-label prospective study assessed older patients naïve to strong opioids presenting with moderate-to-severe chronic pain. Patients were prescribed OXN-PR at an initial dose of 10/5 mg/day for 28 days. In case of insufficient analgesia, the initial daily dose could be increased gradually. The primary efficacy measure was change in pain intensity from baseline, assessed by a ten-point Numeric Rating Scale (NRS) at day 28 (T28). Changes in cognitive state, daily functioning, quality of life, constipation, and other adverse events were assessed. Results Of 53 patients enrolled (mean 81.7±6.2 years [range 70–92 years]), 52 (98.1%) completed the 28-day observation. At T28, the primary end point (≥30% reduction in mean pain from baseline in the absence of bowel function deterioration) was achieved in 38 patients (71.7%). OXN-PR significantly relieved pain (NRS score –3.26; P<0.0001), as well as daily need for rescue paracetamol (from 86.8% at baseline to 40.4% at T28; P<0.001), and reduced impact of pain on daily activities (Brief Pain Inventory Short Form from 6.2±1.5 to 3.4±2.1; P<0.0001). OXN-PR was also associated with significant improvement in daily functioning (Barthel Index from 53.3±14.1 to 61.3±14.3; P<0.01). No changes were observed in cognitive status and bowel function. OXN-PR was well tolerated; only one patient (1.9%) prematurely withdrew from treatment, due to drowsiness. Conclusion Findings from this open-label prospective study suggest that low-dose OXN-PR may be effective and well tolerated for treatment of moderate-to-severe chronic pain in older patients. Besides its effectiveness, these data indicate that low-dose

  2. Radiation leukaemogenesis at low doses DE-FG02-05 ER 63947 Final Technical Report 15 May 2005; 14 May 2010

    SciTech Connect

    Bouffler, Simon

    2010-07-28

    This report provides a complete summary of the work undertaken and results obtained under US Department of Energy grant DF-FG02-05 ER 63947, Radiation leukaemogenesis at low doses. There is ample epidemiological evidence indicating that ionizing radiation is carcinogenic in the higher dose range. This evidence, however, weakens and carries increasing uncertainties at doses below 100-200 mSv. At these low dose levels the form of the dose-response curve for radiation-induced cancer cannot be determined reliably or directly from studies of human populations. Therefore animal, cellular and other experimental systems must be employed to provide supporting evidence on which to base judgements of risk at low doses. Currently in radiological protection a linear non-threshold (LNT) extrapolation of risk estimates derived from human epidemiological studies is used to estimate risks in the dose range of interest for protection purposes. Myeloid leukaemias feature prominently among the cancers associated with human exposures to ionising radiation (eg UNSCEAR 2006; IARC 2000). Good animal models of radiation-induced acute myeloid leukaemia (AML) are available including strains such as CBA, RFM and SJL (eg Major and Mole 1978; Ullrich et al 1976; Resnitzky et al 1985). Early mechanistic studies using cytogenetic methods in these mouse models established that the majority of radiation-induced AMLs carried substantial interstitial deletions in one copy of chromosome (chr) 2 (eg Hayata et al 1983; Trakhtenbrot et al 1988; Breckon et al 1991; Rithidech et al 1993; Bouffler et al 1996). Chr2 aberrations are known to occur in bone marrow cells as early as 24 hours after in vivo irradiation (Bouffler et al 1997). Subsequent molecular mapping studies defined a distinct region of chr2 that is commonly lost in AMLs (Clark et al 1996; Silver et al 1999). Further, more detailed, analysis identified point mutations at a specific region of the Sfpi1/PU.1 haemopoietic transcription factor gene

  3. Summary of the investigation of low temperature, low dose radiation effects on the V-4Cr-4Ti alloy

    SciTech Connect

    Snead, L.L.; Zinkle, S.J.; Alexander, D.J.; Rowcliffe, A.F.; Robertson, J.P.; Eatherly, W.S.

    1998-03-01

    Experimental details, raw data, method of analysis and results are presented for the low-temperature, low-dose HFBR-V1 through V4 irradiation experiments conducted at ORNL on V-4Cr-4Ti specimens (US Fusion Program Heat No. 832665). Four separate capsules were irradiated in the V-15 and V-16 In-Core Thimbles of the High Flux Beam Reactor at the Brookhaven National Laboratory to doses of 0.1 or 0.5 dpa at temperatures between 100 and 505 C. Testing included microhardness, electrical resistivity, tensile properties, and Charpy impact properties.

  4. Chronic exposure to a low dose of ingested petroleum disrupts corticosterone receptor signalling in a tissue-specific manner in the house sparrow (Passer domesticus)

    PubMed Central

    Lattin, Christine R.; Romero, L. Michael

    2014-01-01

    Stress-induced concentrations of glucocorticoid hormones (including corticosterone, CORT) can be suppressed by chronic exposure to a low dose of ingested petroleum. However, endocrine-disrupting chemicals could interfere with CORT signalling beyond the disruption of hormone titres, including effects on receptors in different target tissues. In this study, we examined the effects of 6 weeks of exposure to a petroleum-laced diet (1% oil weight:food weight) on tissue mass and intracellular CORT receptors in liver, fat, muscle and kidney (metabolic tissues), spleen (an immune tissue) and testes (a reproductive tissue). In the laboratory, male house sparrows were fed either a 1% weathered crude oil (n = 12) or a control diet (n = 12); glucocorticoid receptors and mineralocorticoid receptors were quantified using radioligand binding assays. In oil-exposed birds, glucocorticoid receptors were lower in one metabolic tissue (liver), higher in another metabolic tissue (fat) and unchanged in four other tissues (kidney, muscle, spleen and testes) compared with control birds. We saw no differences in mineralocorticoid receptors between groups. We also saw a trend towards reduced mass of the testes in oil-exposed birds compared with controls, but no differences in fat, kidney, liver, muscle or spleen mass between the two groups. This is the first study to examine the effects of petroleum on CORT receptor density in more than one or two target tissues. Given that a chronic low dose of ingested petroleum can affect stress-induced CORT titres as well as receptor density, this demonstrates that oil can act at multiple levels to disrupt an animal’s response to environmental stressors. This also highlights the potential usefulness of the stress response as a bioindicator of chronic crude oil exposure. PMID:27293679

  5. Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain

    PubMed Central

    Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-01-01

    Study Design Retrospective study. Purpose To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Overview of Literature Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Methods Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. Results No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Conclusions Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent

  6. Mitigating effects of L-selenomethionine on low-dose iron ion radiation-induced changes in gene expression associated with cellular stress.

    PubMed

    Nuth, Manunya; Kennedy, Ann R

    2013-07-01

    Ionizing radiation associated with highly energetic and charged heavy (HZE) particles poses a danger to astronauts during space travel. The aim of the present study was to evaluate the patterns of gene expression associated with cellular exposure to low-dose iron ion irradiation, in the presence and absence of L-selenomethionine (SeM). Human thyroid epithelial cells (HTori-3) were exposed to low-dose iron ion (1 GeV/n) irradiation at 10 or 20 cGy with or without SeM pretreatment. The cells were harvested 6 and 16 h post-irradiation and analyzed by the Affymetrix U133Av2 gene chip arrays. Genes exhibiting a 1.5-fold expression cut-off and 5% false discovery rate (FDR) were considered statistically significant and subsequently analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) for pathway analysis. Representative genes were further validated by real-time RT-PCR. Even at low doses of radiation from iron ions, global genome profiling of the irradiated cells revealed the upregulation of genes associated with the activation of stress-related signaling pathways (ubiquitin-mediated proteolysis, p53 signaling, cell cycle and apoptosis), which occurred in a dose-dependent manner. A 24-h pretreatment with SeM was shown to reduce the radiation effects by mitigating stress-related signaling pathways and downregulating certain genes associated with cell adhesion. The mechanism by which SeM prevents radiation-induced transformation in vitro may involve the suppression of the expression of genes associated with stress-related signaling and certain cell adhesion events.

  7. Mitigating effects of L-selenomethionine on low-dose iron ion radiation-induced changes in gene expression associated with cellular stress.

    PubMed

    Nuth, Manunya; Kennedy, Ann R

    2013-07-01

    Ionizing radiation associated with highly energetic and charged heavy (HZE) particles poses a danger to astronauts during space travel. The aim of the present study was to evaluate the patterns of gene expression associated with cellular exposure to low-dose iron ion irradiation, in the presence and absence of L-selenomethionine (SeM). Human thyroid epithelial cells (HTori-3) were exposed to low-dose iron ion (1 GeV/n) irradiation at 10 or 20 cGy with or without SeM pretreatment. The cells were harvested 6 and 16 h post-irradiation and analyzed by the Affymetrix U133Av2 gene chip arrays. Genes exhibiting a 1.5-fold expression cut-off and 5% false discovery rate (FDR) were considered statistically significant and subsequently analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) for pathway analysis. Representative genes were further validated by real-time RT-PCR. Even at low doses of radiation from iron ions, global genome profiling of the irradiated cells revealed the upregulation of genes associated with the activation of stress-related signaling pathways (ubiquitin-mediated proteolysis, p53 signaling, cell cycle and apoptosis), which occurred in a dose-dependent manner. A 24-h pretreatment with SeM was shown to reduce the radiation effects by mitigating stress-related signaling pathways and downregulating certain genes associated with cell adhesion. The mechanism by which SeM prevents radiation-induced transformation in vitro may involve the suppression of the expression of genes associated with stress-related signaling and certain cell adhesion events. PMID:23946774

  8. Radiation leukaemogenesis at low doses DE-FG02-05 ER 63947 Final Technical Report 15 May 2005 14 May 2010

    SciTech Connect

    Bouffler, Simon; Badie, Christophe; Brown, Natalie; Finnon, Rosemary

    2010-05-14

    This report provides a full summary of the results obtained under grant DE-FG02-05ER63947, Radiation Leukaemogenesis at low doses. The studies employed an experimental model of radiation leukaemogenesis with the main aim of identifying key events that convert normal cells into leukaemic cells follwoing exposure to radiation. Important aspect of the work was to understand dose-response relationships and time course relationships for leakaemogenis events. The studies performed provided evidence for direct radiation-induced losses of the Sfpi1/PU.1 gene being critical for induction of the disease. No threshold below 0.1 Gy in the induction of the gene losses was observed. The critical cell type in which the myeloid lekaemias arise has been identified and point mutations in the Sfpi1/PU.1 gene are common in leukaemias. The consequences of the genetic losses and mutation have been examined and these provide evidence of a disruption of differentiation in leukaemic cells. Additional pathways to leukaemogenesis have been identified also. Overall the study provides quantitiative data suitable for testing approaches to modelling of leukaemia rosk at low doses.

  9. [INFLUENCE OF EMOTIONAL STRESS ON CELLULAR IMMUNITY EXPOSED TO LOW DOSE OF GAMMA-RADIATION IN THE REMOTE PERIOD (EXPERIMENTAL STUDY)].

    PubMed

    Utegenova, A; Zhetpisbayev, B; Semenova, Yu; Kydyrmoldina, A; Argynbekova, A

    2016-07-01

    The study aim was to investigate the combined influence of emotional stress and low doses of ionizing radiation (0.2 Gr) on cellular immunity of laboratory animals in the remote period. One hundred and twenty Wistar rats were divided into 4 groups: 1 group control, 2 group - exposed to gamma-radiation, 3 group - exposed to emotional stress, 4 group was exposed to the combined influence of emotional stress and gamma-radiation. Emotional stress was simulated by tail suspension. Animals from groups 2 and 4 were exposed to a single dose of 0.2 Gr 90 days prior the investigation via «TERAGAM» 60Co (ISOTREND spol. s.r.o., Check Republic). The results of our study show that in a remote period after exposure to a low dose of gamma-radiation the decrease of quantitative and increase of qualitative indicators of cellular immunity are observed, which is manifested by lymphopenia and decease of CD3+- CD4+ - and CD8+-lymphocytes subpopulations, and lymphokin-producing capacity of leucocytes. The late phase of stress-reaction is characterized by lymphocytosis, increase in absolute numbers of CD3+- and CD4+- lymphocytes, normal range of CD8+- cells and lymphokin-producing capacity of leucocytes and decrease of immunoregulatory index. PMID:27661286

  10. Impact of chronic exposure to low doses of chlorpyrifos on the intestinal microbiota in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) and in the rat.

    PubMed

    Joly, Claire; Gay-Quéheillard, Jérôme; Léké, André; Chardon, Karen; Delanaud, Stéphane; Bach, Véronique; Khorsi-Cauet, Hafida

    2013-05-01

    The impact of the insecticide chlorpyrifos (CPF) on the mammalian digestive system has been poorly described. The present study aimed at evaluating the effect of chronic, low-dose exposure to CPF on the composition of the gut microbiota in a Simulator of the Human Intestinal Microbial Ecosystem: the SHIME and in rats. The SHIME comprises six reactor vessels (stomach to colon). The colonic segments were inoculated with feces from healthy humans. Then, the simulator was exposed to a daily dose of 1 mg of CPF for 30 days. The changes over time in the populations of bacteria were examined at different time points: prior to pesticide exposure (as a control) and after exposure. In parallel, pregnant rats were gavaged daily with 1 mg/kg of CPF (or vehicle) until the pups were weaned. Next, the rats were gavaged with same dose of CPF until 60 days of age (adulthood). Then, samples of different parts of the digestive tract were collected under sterile conditions for microbiological assessment. Chronic, low-dose exposure to CPF in the SHIME and in the rat was found to induce dysbiosis in the microbial community with, in particular, proliferation of subpopulations of some strains and a decrease in the numbers of others bacteria. In compliance with European guidelines, the use of the SHIME in vitro tool would help to (1) elucidate the final health effect of toxic agents and (2) minimize (though not fully replace) animal testing. Indeed, certain parameters would still have to be studied further in vivo. PMID:23135753

  11. Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction

    SciTech Connect

    Adachi, Naoki; Kubota, Yoshitaka; Kosaka, Kentarou; Akita, Shinsuke; Sasahara, Yoshitarou; Kira, Tomoe; Kuroda, Masayuki; Mitsukawa, Nobuyuki; Bujo, Hideaki; Satoh, Kaneshige

    2015-08-07

    Poor survival is a major problem of adipocyte transplantation. We previously reported that VEGF and MMPs secreted from transplanted adipocytes are essential for angiogenesis and adipogenesis. Pretreatment with low-dose (5 Gy) radiation (LDR) increased VEGF, MMP-2, and HIF-1 alpha mRNA expression in human ceiling culture-derived proliferative adipocytes (hccdPAs). Gene expression after LDR differed between adipose-derived stem cells (hASCs) and hccdPAs. Pretreatment with LDR improved the survival of hccdPAs under hypoxia, which is inevitable in the early stages after transplantation. Upregulation of VEGF and MMP-2 after LDR in hccdPAs is mediated by HIF-1 alpha expression. Our results suggest that pretreatment with LDR may improve adipocyte graft survival in a clinical setting through upregulation of VEGF and MMP-2 via HIF-1 alpha. - Highlights: • Ceiling culture-derived proliferative adipocytes (ccdPAs) react to radiation. • Low-dose radiation (LDR) pretreatment improves survival of ccdPAs under hypoxia. • Gene expression after LDR differs between ccdPAs and adipose-derived stem cells. • LDR-induced increase in MMP-2 and VEGF is dependent on HIF-1 alpha induction. • LDR pretreatment may improve the adipocyte graft survival rate in clinical settings.

  12. Cell Type-dependent Gene Transcription Profile in Three Dimensional Human Skin Tissue Model Exposed to Low Doses of Ionizing Radiation: Implications for Medical Exposures

    SciTech Connect

    Freiin von Neubeck, Claere H.; Shankaran, Harish; Karin, Norman J.; Kauer, Paula M.; Chrisler, William B.; Wang, Xihai; Robinson, Robert J.; Waters, Katrina M.; Tilton, Susan C.; Sowa, Marianne B.

    2012-04-17

    The concern over possible health risks from exposures to low doses of ionizing radiation has been driven largely by the increase in medical exposures, the routine implementation of X-ray backscatter devices for airport security screening, and, most recently, the nuclear incident in Japan. Due to a paucity of direct epidemiological data at very low doses, cancer risk must be estimated from high dose exposure scenarios. However, there is increasing evidence that low and high dose exposures result in different signaling events and may have different mechanisms of cancer induction. We have examined the radiation induced temporal response of an in vitro three dimensional (3D) human skin tissue model using microarray-based transcriptional profiling. Our data shows that exposure to 100 mGy of X-rays is sufficient to affect gene transcription. Cell type specific analysis showed significant changes in gene expression with the levels of > 1400 genes altered in the dermis and > 400 genes regulated in the epidermis. The two cell types rarely exhibited overlapping responses at the mRNA level. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) measurements validated the microarray data in both regulation direction and value. Key pathways identified relate to cell cycle regulation, immune responses, hypoxia, reactive oxygen signaling, and DNA damage repair. We discuss in particular the role of proliferation and emphasizing how the disregulation of cellular signaling in normal tissue may impact progression towards radiation induced secondary diseases.

  13. Calmodulin Mediates DNA Repair Pathways Involving H2AX in Response to Low-Dose Radiation Exposure of RAW 264.7 Macrophages

    SciTech Connect

    Smallwood, Heather S.; Lopez Ferrer, Daniel; Eberlein, P. Elis; Watson, David J.; Squier, Thomas C.

    2009-02-05

    Understanding the molecular mechanisms that modulate macrophage radioresistance is necessary for the development of effective radiation therapies, as tumor-associated macrophages promote both angiogenesis and matrix remodeling that, in turn, enhance metastasis. In this respect, we have identified a dose-dependent increase in the abundance of the calcium regulatory protein calmodulin (CaM) in RAW 264.7 macrophages upon irradiation. CaM overexpression results in increased macrophage survival following radiation exposure, acting to diminish the sensitivity to low-dose exposures. Increases in CaM abundance also result in an increase in the number of phosphorylated histone H2AX protein complexes associated with DNA repair following macrophage irradiation, with no change in the extent of double-stranded DNA damage. In comparison, when NFκB-dependent pathways are inhibited, through the expression of a dominant-negative IκB construct, there is no significant increase in phosphorylated H2AX upon irradiation. These results indicate that the molecular basis for the up-regulation of histone H2AX mediated DNA-repair pathways is not the result of nonspecific NFκB-dependent pathways or a specific threshold of DNA damage. Rather, increases in CaM abundance act to minimize the low-dose hypersensitivity to radiation to enhance macrophage radioresistance through processes that include the upregulation of DNA repair pathways involving histone protein H2AX phosphorylation.

  14. Significance of low-dose radiation distribution in development of radiation pneumonitis after helical-tomotherapy-based hypofractionated radiotherapy for pulmonary metastases.

    PubMed

    Jo, In-Young; Kay, Chul-Seung; Kim, Ji-Yoon; Son, Seok-Hyun; Kang, Yong-Nam; Jung, Ji-Young; Kim, Ki-Jun

    2014-01-01

    Hypofractionated radiotherapy (HRT) is now commonly used for pulmonary malignancies, since a tumoricidal dose can be accurately delivered to the target without a consequential dose to adjacent normal tissues. However, radiation pneumonitis (RP) is still a major problem after HRT. To determine the significant parameters associated with developing RP, we retrospectively investigated data from patients with lung metastases treated with HRT using helical tomotherapy. A total of 45 patients were included in the study and the median age was 53 years old. The median prescriptive doses were 50 Gy to the internal target volume and 40 Gy to the planning target volume in 10 fractions over 2 weeks. RP was diagnosed by chest X-ray or computed tomography after HRT, and its severity was determined by CTCAE version 4.0. The incidence of symptomatic RP was 26.6%. Univariate analysis indicated that mean lung doses, V5, V10, V15, V20 and V25 were associated with the development of symptomatic RP (P < 0.05). However, multivariate analysis indicated that only V5 was associated with the development of symptomatic RP (P = 0.019). From the ROC curve, V5 was the most powerful predictor of symptomatic RP, and its AUC (area under curve) was 0.780 (P = 0.004). In addition, the threshold value of V5 for the development of symptomatic RP was 65%. A large distribution of low-dose radiation resulted in a higher risk of lung toxicity. So, to prevent symptomatic RP, it is recommended that the V5 be limited to <65%, in addition to considering conventional dosimetric factors. However, further clinical study must be undertaken in order to confirm this result.

  15. Neurobehavioral deficits and brain oxidative stress induced by chronic low dose exposure of persistent organic pollutants mixture in adult female rat.

    PubMed

    Lahouel, Asma; Kebieche, Mohamed; Lakroun, Zohra; Rouabhi, Rachid; Fetoui, Hamadi; Chtourou, Yassine; Djamila, Zama; Soulimani, Rachid

    2016-10-01

    Persistent organic pollutants (POPs) are long-lived organic compounds that are considered one of the major risks to ecosystem and human health. Recently, great concerns are raised about POPs mixtures and its potential toxicity even in low doses of daily human exposure. The brain is mostly targeted by these lipophilic compounds because of its important contain in lipids. So, it would be quite interesting to study the effects of exposure to these mixtures and evaluate their combined toxicity on brain cells. The present study was designed to characterize the cognitive and locomotors deficits and brain areas redox status in rat model. An orally chronic exposure to a representative mixture of POPs composed of endosulfan (2.6 μg/kg), chlorpyrifos (5.2 μg/kg), naphthalene (0.023 μg/kg) and benzopyrane (0.002 μg/kg); the same mixture with concentration multiplied by 10 and 100 was also tested. Exposed rats have shown a disturbance of memory and a decrease in learning ability concluded by Morris water maze and the open field tests results and anxiolytic behaviour in the test of light/dark box compared to control. Concerning brain redox homeostasis, exposed rats have shown an increased malondialdehyde (MDA) amount and an alteration in glutathione (GSH) levels in both the brain mitochondria and cytosolic fractions of the cerebellum, striatum and hippocampus. These effects were accompanied by a decrease in levels of cytosolic glutathione S-transferase (GST) and a highly significant increase in superoxide dismutase (SOD) and catalase (CAT) activities in both cytosolic and mitochondrial fractions. The current study suggests that environmental exposure to daily even low doses of POPs mixtures through diet induces oxidative stress status in the brain and especially in the mitochondria with important cognitive and locomotor behaviour variations in the rats.

  16. Neurobehavioral deficits and brain oxidative stress induced by chronic low dose exposure of persistent organic pollutants mixture in adult female rat.

    PubMed

    Lahouel, Asma; Kebieche, Mohamed; Lakroun, Zohra; Rouabhi, Rachid; Fetoui, Hamadi; Chtourou, Yassine; Djamila, Zama; Soulimani, Rachid

    2016-10-01

    Persistent organic pollutants (POPs) are long-lived organic compounds that are considered one of the major risks to ecosystem and human health. Recently, great concerns are raised about POPs mixtures and its potential toxicity even in low doses of daily human exposure. The brain is mostly targeted by these lipophilic compounds because of its important contain in lipids. So, it would be quite interesting to study the effects of exposure to these mixtures and evaluate their combined toxicity on brain cells. The present study was designed to characterize the cognitive and locomotors deficits and brain areas redox status in rat model. An orally chronic exposure to a representative mixture of POPs composed of endosulfan (2.6 μg/kg), chlorpyrifos (5.2 μg/kg), naphthalene (0.023 μg/kg) and benzopyrane (0.002 μg/kg); the same mixture with concentration multiplied by 10 and 100 was also tested. Exposed rats have shown a disturbance of memory and a decrease in learning ability concluded by Morris water maze and the open field tests results and anxiolytic behaviour in the test of light/dark box compared to control. Concerning brain redox homeostasis, exposed rats have shown an increased malondialdehyde (MDA) amount and an alteration in glutathione (GSH) levels in both the brain mitochondria and cytosolic fractions of the cerebellum, striatum and hippocampus. These effects were accompanied by a decrease in levels of cytosolic glutathione S-transferase (GST) and a highly significant increase in superoxide dismutase (SOD) and catalase (CAT) activities in both cytosolic and mitochondrial fractions. The current study suggests that environmental exposure to daily even low doses of POPs mixtures through diet induces oxidative stress status in the brain and especially in the mitochondria with important cognitive and locomotor behaviour variations in the rats. PMID:27240828

  17. Effect of low doses of ionizing radiation on cells cultured from the hematopoietic tissue of the Dublin Bay prawn, Nephrops norvegicus.

    PubMed

    Mothersill, C; Lyng, F; Mulford, A; Seymour, C; Cottell, D; Lyons, M; Austin, B

    2001-09-01

    Explant cultures from the hematopoietic tissue of the Dublin Bay prawn, Nephrops norvegicus, were exposed to low doses of (60)Co gamma radiation. Cells growing from the explants were examined 7 days after irradiation using light and transmission electron microscopy and were also tested for their ability to produce signals indicative of a bystander effect. The exposed cultures displayed pronounced damage and were orders of magnitude more sensitive than the data in the literature would suggest for arthropod cells. The cultures were also more sensitive than mammalian cells that were exposed to similar doses. Cellular abnormalities included damage to cytoplasmic organelles, particularly the cytoskeleton. Abnormal mitochondria were also prominent. At low doses (0.5 Gy), nuclear damage was not apparent in the cultures, but there was evidence of a dose-dependent increase in apoptosis. The irradiated cultures released a factor into the medium that was capable of inducing apoptosis and cell death in unirradiated fish and human cells. This bystander effect was of a similar magnitude to that reported for mammalian cell systems. It is suggested that these crustaceans may be highly sensitive to radiation, unlike terrestrial arthropods and certain other invertebrates, which are generally considered to be radioresistant.

  18. Enhancement of viability of radiosensitive (PBMC) and resistant (MDA-MB-231) clones in low-dose-rate cobalt-60 radiation therapy*

    PubMed Central

    Falcão, Patrícia Lima; Motta, Bárbara Miranda; de Lima, Fernanda Castro; Lima, Celso Vieira; Campos, Tarcísio Passos Ribeiro

    2015-01-01

    Objective In the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231) cells line and radiosensitive peripheral blood mononuclear cells (PBMC), as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and Methods The cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min–1 and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results Radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB- 231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48–72 hours post-radiation. Conclusion Low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer. PMID:26185342

  19. Effect of low-dose diuretics on the level of serum cystatin C and prognosis in patients with asymptomatic chronic heart failure

    PubMed Central

    ZHANG, YUAN; LI, YANMING; CHENG, GUANCHANG

    2015-01-01

    The aim of the present study was to investigate the effect of low-dose diuretics on the serum cystatin C (CysC) and serum creatinine (Scr) levels, and on the prognosis in patients with asymptomatic chronic heart failure (HF). A total of 66 asymptomatic chronic HF patients were divided into the observation and control groups (n=33 in each group). Patients in the control group were treated with a routine treatment, while the patients in the observation group were treated with the diuretic hydrochlorothiazide along with the same routine treatment as the control group. The left ventricular ejection fraction (LVEF), serum CysC levels, Scr levels, heart function, prognosis, adverse reactions and complications of the patients in the two groups were compared prior to and following treatment. The LVEF increased in the two groups following treatment, while the levels of serum CysC and Scr decreased. The LVEF in the observation group increased following treatment for 1, 3 and 6 months compared with the LVEF values in the control group. In addition, the levels of serum CysC and Scr in the observation group were found to be lower compared with those in the control group (P<0.05). The incidence of adverse prognosis following treatment for 6 months in the observation group was lower compared with that in the control group (P<0.05). The proportion of HF patients with New York Heart Association (NYHA) class I and II increased following treatment for 6 months in the two groups (P<0.05). However, in the observation group, a higher number of patients exhibited class I and II disease after treatment for 6 months compared with the number in the control group (P<0.05). Furthermore, no statistically significant difference was observed between adverse reactions and complications in the two groups (P>0.05). In conclusion, low-dose diuretics may effectively improve the cardiac and renal functions and prognosis in asymptomatic chronic HF patients, without increasing the incidence of side

  20. Low dose abdominal radiation as a docetaxel chemosensitizer for recurrent epithelial ovarian cancer: A phase I study of the Gynecologic Oncology Group

    PubMed Central

    Kunos, Charles A.; Sill, Michael W.; Buekers, Thomas E.; Walker, Joan L.; Schilder, Jeanne M.; Yamada, S. Diane; Waggoner, Steven E.; Mohiuddin, Mohammed; Fracasso, Paula M.

    2010-01-01

    Objectives To determine the maximum tolerated dose and dose-limiting toxicity (DLT) of whole abdomen radiation as a chemosensitizer of weekly docetaxel for women with recurrent epithelial ovarian fallopian tube, or peritoneal cancers. Patients and methods Women were enrolled on one of three dose levels of docetaxel (20, 25, or 30 mg/m2) administered weekly with concurrent low dose whole abdominal radiation given as 60 cGy bid two days weekly for a total of 6 weeks. Results Thirteen women were enrolled and received 70 weekly treatments of docetaxel in combination with radiation therapy. At the first dose level, docetaxel 25 mg/m2, grade 3 fatigue and thrombocytopenia were observed. At the next dose level, docetaxel 30 mg/m2, grade 3 febrile neutropenia, grade 4 thrombocytopenia with epistaxis and grade 3 diarrhea were observed. Given these dose-limiting toxicities, a lower dose of docetaxel 20 mg/m2 was administered and found to be tolerable. No objective responses were observed among the 10 patients with measurable disease; however, the median progression-free survival (PFS) in all patients was 3.3 months, and 3 of the patients with measurable disease were free of tumor progression after 6 months (30%; 90% Confidence Interval 8.7–61%). Conclusions Twice weekly low dose whole abdomen radiation during weekly docetaxel 20 mg/m2 was well-tolerated. Given the PFS demonstrated in these women with resistant ovarian cancer, further study of whole abdominal radiation and concurrent chemotherapy may be warranted. PMID:21075438

  1. DETECTION OF LOW DOSE RADIATION-AND CHEMICALLY-INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAYS

    EPA Science Inventory

    Rapid, sensitive and simple assays for radiation- and chemically-induced DNA damage can be of significant benefit to a number of fields including radiation biology, clinical research, and environmental monitoring. Although temperature-induced DNA strand separation has been use...

  2. Regulation Of Nf=kb And Mnsod In Low Dose Radiation Induced Adaptive Protection Of Mouse And Human Skin Cells

    SciTech Connect

    Jian Li

    2012-11-07

    A sampling of publications resulting from this grant is provided. One is on the subject of NF-κB-Mediated HER2 Overexpression in Radiation-Adaptive Resistance. Another is on NF-κB-mediated adaptive resistance to ionizing radiation.

  3. γ-H2AX responds to DNA damage induced by long-term exposure to combined low-dose-rate neutron and γ-ray radiation.

    PubMed

    Zhang, Junlin; He, Ying; Shen, Xianrong; Jiang, Dingwen; Wang, Qingrong; Liu, Qiong; Fang, Wen

    2016-01-01

    Risk estimates for low-dose radiation (LDR) remain controversial. The possible involvement of DNA repair-related genes in long-term low-dose-rate neutron-gamma radiation exposure is poorly understood. In this study, 60 rats were divided into control groups and irradiated groups, which were exposed to low-dose-rate n-γ combined radiation (LDCR) for 15, 30, or 60 days. The effects of different cumulative radiation doses on peripheral blood cell (PBC), subsets of T cells of peripheral blood lymphocytes (PBL) and DNA damage repair were investigated. Real-time PCR and immunoblot analyses were used to detect expression of DNA DSB-repair-related genes involved in the NHEJ pathway, such as Ku70 and Ku80, in PBL. The mRNA level of H2AX and the expression level of γ-H2AX were detected by real-time PCR, immunoblot, and flow cytometry. White blood cells (WBC) and platelets (PLT) of all ionizing radiation (IR) groups decreased significantly, while no difference was seen between the 30 day and 60 day exposure groups. The numbers of CD3(+), CD4(+) T cells and CD4(+)/CD8(+) in the PBL of IR groups were lower than in the control group. In the 30 day and 60 day exposure groups, CD8(+) T cells decreased significantly. Real-time PCR and immunoblot results showed no significant difference in the mRNA and protein expression of Ku70 and Ku80 between the control groups and IR groups. However, the mRNA of H2AX increased significantly, and there was a positive correlation with dose. There was no difference in the protein expression of γ-H2AX between 30 day and 60 day groups, which may help to explain the damage to PBL. In conclusion, PBL damage increased with cumulative dose, suggesting that γ-H2AX, but neither Ku70 nor Ku80, plays an important role in PBL impairment induced by LDCR.

  4. What Have "Omics" Taught Us about the Health Risks Associated with Exposure to Low Doses of Ionizing Radiation

    SciTech Connect

    Morgan, William F.; Sowa, Marianne B.

    2011-04-27

    There is a plethora of data available on the DNA damages associated with exposures to ionizing radiation and the subsequent cellular responses. Indeed, much of radiation research has focused on these initial insults and induced responses, particularly DNA repair, cell signaling pathways, cell cycle checkpoint control, mutation induction, chromosomal rearrangements, transformation and apoptosis etc. While many of these endpoints correlate with exposure dose, few, if any, provide substantive information on human health risk(s) associated with radiation exposure. Here the contribution of recent advances in high throughput ‘omics technologies are evaluated to examine what they have taught us about health risk(s) to humans associated with exposure to ionizing radiation.

  5. Protective Effects of Hydrogen against Low-Dose Long-Term Radiation-Induced Damage to the Behavioral Performances, Hematopoietic System, Genital System, and Splenic Lymphocytes in Mice

    PubMed Central

    Lei, Xiao; Zhao, Hainan; Liu, Pengfei; Xu, Yang; Chen, Yuanyuan; Chuai, Yunhai

    2016-01-01

    Molecular hydrogen (H2) has been previously reported playing an important role in ameliorating damage caused by acute radiation. In this study, we investigated the effects of H2 on the alterations induced by low-dose long-term radiation (LDLTR). All the mice in hydrogen-treated or radiation-only groups received 0.1 Gy, 0.5 Gy, 1.0 Gy, and 2.0 Gy whole-body gamma radiation, respectively. After the last time of radiation exposure, all the mice were employed for the determination of the body mass (BM) observation, forced swim test (FST), the open field test (OFT), the chromosome aberration (CA), the peripheral blood cells parameters analysis, the sperm abnormality (SA), the lymphocyte transformation test (LTT), and the histopathological studies. And significant differences between the treatment group and the radiation-only groups were observed, showing that H2 could diminish the detriment induced by LDLTR and suggesting the protective efficacy of H2 in multiple systems in mice against LDLTR. PMID:27774116

  6. The genetic basis of cellular recovery from radiation damage: Response of the radiosensitive irs lines to low-dose-rate irradiation

    SciTech Connect

    Thacker, J.; Wilkinson, R.E.

    1995-12-01

    Recovery from the lethal effects of irradiation is commonly found when cultured mammalian cells are irradiated at low dose rates when compared to the same cells irradiated at higher dose rates. However, this cellular recovery process is severely reduced or absent in a number of radiosensitive cell lines, including those derived from the human disorder ataxia telangiectasia (AT). The genetic and molecular basis of such recovery processes is not understood, despite their importance. The responses of cells of three further radiosensitive lines, irs1, irs2 and irs3, shown previously to be mutated in different genes, to low-dose-rate radiation are now presented. Plateau-phase cultures of cells of the irs2 line were found to have little or no cellular recovery, while irs1 and irs3 had considerable recovery potential. In comparing the known properties of the radiosensitive lines. lacking cellular recovery, including xrs, XR-1 and scid as well as AT and irs2, it is argued that the gene products lacking in these lines normally act coordinately in a specific damage-recognition pathway. The recovery pathway is likely to be associated with the rejoining of DNA double-strand breaks, since several of these recovery-defective lines have a measurable deficiency in break repair. 67 refs., 5 figs., 2 tabs.

  7. RADIATION SENSITIVITY & PROCESSING OF DNA DAMAGE FOLLOWING LOW DOSES OF GAMMA-RAY ALPHA PARTICLES & HZE IRRADIATION OF NORMAL DSB REPAIR DEFICIENT CELLS

    SciTech Connect

    O'Neil, Peter

    2009-05-15

    Non-homologous end joining (NHEJ) predominates in the repair of DNA double strand breaks (DSB) over homologous recombination (HR). NHEJ occurs throughout the cell cycle whereas HR occurs in late S/G2 due to the requirement of a sister chromatid (Rothkamm et al, Mol Cell Biol 23 5706-15 [2003]). To date evidence obtained with DSB repair deficient cells using pulsed-field gel electrophoresis has revealed the major pathway throughout all phases of the cell cycle for processing high dose induced DSBs is NHEJ (Wang et al, Oncogene 20 2212-24 (2001); Pluth et al, Cancer Res. 61 2649-55 [2001]). These findings however were obtained at high doses when on average >> 20-30 DSBs are formed per cell. The contribution of the repair pathways (NHEJ and HR) induced in response to DNA damage during the various phases of the cell cycle may depend upon the dose (the level of initial DSBs) especially since low levels of DSBs are induced at low dose. To date, low dose studies using NHEJ and HR deficient mutants have not been carried out to address this important question with radiations of different quality. The work presented here leads us to suggest that HR plays a relatively minor role in the repair of radiation-induced prompt DSBs. SSBs lead to the induction of DSBs which are associated specifically with S-phase cells consistent with the idea that they are formed at stalled replication forks in which HR plays a major role in repair. That DNA-PKcs is in some way involved in the repair of the precursors to replication-induced DSB remains an open question. Persistent non-DSB oxidative damage also leads to an increase in RAD51 positive DSBs. Both simple and complex non-DSB DNA damage may therefore contribute to indirect DSBs induced by ionising radiation at replication forks.

  8. Association of Chromosome Translocation Rate with Low Dose Occupational Radiation Exposures in U.S. Radiologic Technologists

    PubMed Central

    Little, Mark P.; Kwon, Deukwoo; Doi, Kazataka; Simon, Steven L.; Preston, Dale L.; Doody, Michele M.; Lee, Terrence; Miller, Jeremy S.; Kampa, Diane M.; Bhatti, Parveen; Tucker, James D.; Linet, Martha S.; Sigurdson, Alice J.

    2016-01-01

    Chromosome translocations are a well-recognized biological marker of radiation exposure and cancer risk. However, there is uncertainty about the lowest dose at which excess translocations can be detected, and whether there is temporal decay of induced translocations in radiation-exposed populations. Dosimetric uncertainties can substantially alter the shape of dose-response relationships; although regression-calibration methods have been used in some datasets, these have not been applied in radio-occupational studies, where there are also complex patterns of shared and unshared errors that these methods do not account for. In this article we evaluated the relationship between estimated occupational ionizing radiation doses and chromosome translocation rates using fluorescent in situ hybridization in 238 U.S. radiologic technologists selected from a large cohort. Estimated cumulative red bone marrow doses (mean 29.3 mGy, range 0–135.7 mGy) were based on available badge–dose measurement data and on questionnaire-reported work history factors. Dosimetric assessment uncertainties were evaluated using regression calibration, Bayesian and Monte Carlo maximum likelihood methods, taking account of shared and unshared error and adjusted for overdispersion. There was a significant dose response for estimated occupational radiation exposure, adjusted for questionnaire-based personal diagnostic radiation, age, sex and study group (5.7 translocations per 100 whole genome cell equivalents per Gy, 95% CI 0.2, 11.3, P = 0.0440). A significant increasing trend with dose continued to be observed for individuals with estimated doses <100 mGy. For combined estimated occupational and personal-diagnostic-medical radiation exposures, there was a borderline-significant modifying effect of age (P 0.0704), but little evidence (P > 0.5) of temporal decay of induced translocations. The three methods of analysis to adjust for dose uncertainty gave similar results. In summary, chromosome

  9. Evaluation of continuous low dose rate versus acute single high dose rate radiation combined with oncolytic viral therapy for prostate cancer

    PubMed Central

    LIU, CHUNYAN; ZHANG, YONGGANG; LIU, MINZHI MAGGIE; ZHOU, HAOMING; CHOWDHURY, WASIM H.; LUPOLD, SHAWN E.; DEWEESE, TED L.; RODRIGUEZ, RONALD

    2011-01-01

    Purpose Conditionally Replicative Adenovirus (CRAd) has been previously demonstrated to augment the activity of radiation, resulting in synergy of cell kill. However, previous models combining radiation with CRAd have not focused on the methods of radiation delivery. Materials and methods We model the combination of a novel prostate-specific CRAd, Ad5 PSE/PBN E1A-AR (Ad5: adenovirus 5; PSE: prostate-specific enhancer; PBN: rat probasin promoter; E1A: early region 1A; AR: androgen receptor), with radiation delivered both acutely and continuously, in an effort to better mimic the potential clinical modes of prostate cancer radiotherapy. Results We demonstrate that pre-treatment of cells with acute single high dose rate (HDR) radiation 24 hours prior to viral infection results in significantly enhanced viral replication and virus-mediated cell death. In addition, this combination causes increased level of γ-H2AX (Phosphorylated histone protein H2AX on serine 139), a marker of double-stranded DNA damage and an indirect measure of nuclear fragmentation. In contrast, continuous low dose rate (LDR) radiation immediately following infection of the same CRAd results in no enhancement of viral replication, and only additive effects in virus-mediated cell death. Conclusions These data provide the first direct assessment of the real-time impact of radiation on viral replication and the first comparison of the effect of radiation delivery on the efficacy of CRAd virotherapy. Our data demonstrate substantial differences in CRAd efficacy based on the mode of radiation delivery. PMID:20201650

  10. The Effects of Low Dose-Rate Ionizing Radiation on the Shapes of Transients in the LM124 Operational Amplifier

    NASA Technical Reports Server (NTRS)

    Buchner, Stephen; McMorrow, Dale; Roche, Nicholas; Dusseau, Laurent; Pease, Ron L.

    2008-01-01

    Shapes of single event transients (SETs) in a linear bipolar circuit (LM124) change with exposure to total ionizing dose (TID) radiation. SETs shape changes are a direct consequence of TID-induced degradation of bipolar transistor gain. A reduction in transistor gain causes a reduction in the drive current of the current sources in the circuit, and it is the lower drive current that most affects the shapes of large amplitude SETs.

  11. Effects of low-dose cranial radiation on growth hormone secretory dynamics and hypothalamic-pituitary function

    SciTech Connect

    Costin, G.

    1988-08-01

    Spontaneous growth hormone (GH) secretory dynamics and hypothalamic-pituitary function were studied in 16 long-term survivors of acute lymphoblastic leukemia who were aged 9 to 15 1/2 years and had been treated with prophylactic central nervous system radiation and combined chemotherapy. At the time of study, the mean height was -1.5 SD score below the mean, less than genetic potential, and significantly less than the mean pretreatment height of -0.25 SD score. Height velocity was subnormal for age and sexual stage in all patients. Two patients had compensated hypothyroidism, and four had evidence of gonadal failure. In 11 patients, the peak GH level after two provocative tests was below 10 micrograms/L, which was consistent with GH deficiency. In ten of 13 patients tested, spontaneous GH secretion determined by a 24-hour GH concentration (GHC), GH pulse amplitude, frequency of GH pulses greater than or equal to 5 micrograms/L, and GH peak during wake and sleep hours was significantly less than in normal height controls. Although in three pubertal patients the 24-hour GHC was within normal limits, the GHC during sleep hours, GH pulse amplitude during 24 hours and sleep hours, and peak GH during wake hours were significantly less than in normal height controls. In all pubertal and in two of the prepubertal patients, the somatomedin C (SmC) level was significantly less than in controls. The 24-hour GHC correlated well with the GHC during sleep, peak-stimulated GH level, gonadal steroid level, and the SmC level, but not with height velocity, dose of radiation, or age at radiation. A significant increase in height velocity and the SmC level was noted in all patients treated with GH. These results indicate that GH deficiency occurs after 18 to 24 Gy of cranial radiation and that the puberty-associated growth spurt may mask the decline in height velocity owing to GH deficiency.

  12. Long-term effects of low-dose proton radiation on immunity in mice: shielded vs. unshielded

    NASA Technical Reports Server (NTRS)

    Pecaut, Michael J.; Gridley, Daila S.; Nelson, Gregory A.

    2003-01-01

    BACKGROUND: Outside the protection of the terrestrial environment, astronauts on any long-term missions will unavoidably be exposed to fields of charged particle radiation dominated by protons. These fields and their biological risks are modified in complex ways by the presence of protective shielding. METHODS: To examine the long-term effects of space-like proton exposures on immune status, we treated female C57BL/6 mice with 3 or 4 Gy of 250 MeV monoenergetic protons or the complex space-like radiation field produced after 250 MeV protons are transported through 15 g x cm(-2) aluminum shielding. The animals were euthanized 122 d post-irradiation and lymphocyte phenotypes, hematological parameters, and lymphocyte blastogenesis were characterized. RESULTS: There were significant dose-dependent decreases in macrophage, CD3+/CD8+ T, NK, platelet, and red blood cell populations, as well as low hematocrit and hemoglobin levels. In contrast, dose-dependent increases in spontaneous, but not mitogen-induced, blastogenesis were noted. The differences in dose composition between pristine and shielded proton fields did not lead to significant effects in most measures, but did result in significant changes in monocyte and macrophage populations and spontaneous blastogenesis in the spleen. CONCLUSIONS: The data indicate that whole body exposure to proton radiation at doses of the order of large solar particle events or clinical treatment fractions may have long-term effects on immune system status.

  13. Chronic exposure of mice to environmentally relevant, low doses of cadmium leads to early renal damage, not predicted by blood or urine cadmium levels.

    PubMed

    Thijssen, Sandy; Maringwa, John; Faes, Christel; Lambrichts, Ivo; Van Kerkhove, Emmy

    2007-01-01

    Mice were exposed to cadmium (Cd) concentrations ranging from 0 to 100mg CdCl(2)/l in the drinking water for 1, 4, 8, 16 and 23 weeks. Urine samples were taken regularly, Cd content was determined in blood, liver, kidney and urine and histological analyses of the kidney were performed. Kidney cortex Cd content increased linearly with time and dose, while blood levels reached a plateau at 8 weeks and liver at 16 weeks in mice exposed to 100mg CdCl(2)/l after which both started to decrease. Urinary Cd levels were not correlated with the kidney Cd content. A multivariate regression model taking into account the actual Cd intake, calculated from the volume of water taken in by each animal and the exposure concentration, confirmed that blood is an indicator of acute exposure, while kidney Cd content is a reliable indicator of chronic exposure. The urinary protein content was significantly increased from 16 weeks on in mice exposed to 100mg CdCl(2)/l (p<0.05), while other signs of proximal tubular damage (glucosuria, enzymuria) were not detected. Histologically more vacuoles and lysosomes were present in the proximal tubule cells with increasing time and dose. The results indicate that chronic exposure to low doses of Cd induced functional and histological signs of early damage at concentrations in or below the ones generally accepted as safe. Our study does not corroborate the statement that urine Cd levels are a reliable indicator of total Cd body burden, at least when the body burden is low.

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

    PubMed

    Hammer, Gaël P; Scheidemann-Wesp, Ulrike; Samkange-Zeeb, Florence; Wicke, Henryk; Neriishi, Kazuo; Blettner, Maria

    2013-08-01

    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.

  15. Influence mechanism of low-dose ionizing radiation on Escherichia coli DH5α population based on plasma theory and system dynamics simulation.

    PubMed

    Sun, Yi; Hu, Dawei; Li, Liang; Jing, Zheng; Wei, Chuanfeng; Zhang, Lantao; Fu, Yuming; Liu, Hong

    2016-01-01

    It remains a mystery why the growth rate of bacteria is higher in low-dose ionizing radiation (LDIR) environment than that in normal environment. In this study, a hypothesis composed of environmental selection and competitive exclusion was firstly proposed from observed phenomena, experimental data and microbial ecology. Then a LDIR environment simulator (LDIRES) was built to cultivate a model organism of bacteria, Escherichia coli (E. coli) DH5α, the accurate response of bacterial population to ionizing radiation intensity variation was measured experimentally, and then the precise relative dosage of ionizing radiation E. coli DH5α population received was calculated by finite element analysis based on drift-diffusion equations of plasma. Finally, a highly valid mathematical model expressing the relationship between E. coli DH5α population and LDIR intensity was developed by system dynamics based on hypotheses, experimental data and microbial ecology. Both experiment and simulation results clearly showed that the E. coli DH5α individuals with greater specific growth rate and lower substrate consumption coefficient would adapt and survive in LDIR environment and those without such adaptability were finally eliminated under the combined effects of ionizing radiation selection and competitive exclusion.

  16. “Denervation” of autonomous nervous system in idiopathic pulmonary arterial hypertension by low-dose radiation: a case report with an unexpected outcome

    PubMed Central

    Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul; Oezkan, Filiz; Mahnkopf, Christian; Grabenbauer, Gerhard; Kreczy, Alfons; Bartunek, Rudolf; Darwiche, Kaid; Freitag, Lutz; Li, Qiang; Huang, Haidong; Vogl, Thomas; LePilvert, Patrick; Tsiouda, Theodora; Tsakiridis, Kosmas; Zarogoulidis, Konstantinos; Brachmann, Johannes

    2014-01-01

    Vasointestinal peptide metabolism plays a key physiological role in multimodular levels of vasodilatory, smooth muscle cell proliferative, parenchymal, and inflammatory lung reactions. In animal studies, vasointestinal peptide relaxes isolated pulmonary arterial segments from several mammalian species in vitro and neutralizes the pulmonary vasoconstrictor effect of endothelin. In some animal models, it reduces pulmonary vascular resistance in vivo and in monocrotaline-induced pulmonary hypertension. A 58-year-old woman presented with dyspnea and mild edema of the lower extremities. A bronchoscopy was performed without any suspicious findings suggesting a central tumor or other infiltrative disease. Endobronchial ultrasound revealed enlarged pulmonary arteries containing thrombi, a few enlarged lymph nodes, and enlarged mediastinal tissue anatomy with suspicion for mediastinal infiltration of a malignant process. We estimated that less than 10% of the peripheral vascular bed of the lung was involved in direct consolidated fibrosis as demonstrated in the left upper lobe apex. Further, direct involvement of fibrosis around the main stems of the pulmonary arteries was assumed to be low from positron emission tomography and magnetic resonance imaging scans. Assuming a positive influence of low-dose radiation, it was not expected that this could have reduced pulmonary vascular resistance by over two thirds of the initial result. However; it was noted that this patient had idiopathic pulmonary arterial hypertension mixed with “acute” (mediastinal) fibrosis which could have contributed to the unexpected success of reduction of pulmonary vascular resistance. To the best of our knowledge, this is the first report of successful treatment of idiopathic pulmonary arterial hypertension, probably as a result of low-dose radiation to the pulmonary arterial main stems. The patient continues to have no specific complaints concerning her idiopathic pulmonary arterial hypertension

  17. A semi-automated FISH-based micronucleus-centromere assay for biomonitoring of hospital workers exposed to low doses of ionizing radiation

    PubMed Central

    VRAL, ANNE; DECORTE, VEERLE; DEPUYDT, JULIE; WAMBERSIE, ANDRÉ; THIERENS, HUBERT

    2016-01-01

    The aim of the present study was to perform cytogenetic analysis by means of a semi-automated micro-nucleus-centromere assay in lymphocytes from medical radiation workers. Two groups of workers receiving the highest occupational doses were selected: 10 nuclear medicine technicians and 10 interventional radiologists/cardiologists. Centromere-negative micronucleus (MNCM−) data, obtained from these two groups of medical radiation workers were compared with those obtained in matched controls. The blood samples of the matched controls were additionally used to construct a 'low-dose' (0–100 mGy) MNCM− dose-response curve to evaluate the sensitivity and suitability of the micronucleus-centromere assay as an 'effect' biomarker in medical surveillance programs. The physical dosimetry data of the 3 years preceding the blood sampling, based on single or double dosimetry practices, were collected for the interpretation of the micronucleus data. The in vitro radiation results showed that for small sized groups, semi-automated scoring of MNCM− enables the detection of a dose of 50 mGy. The comparison of MNCM− yields in medical radiation workers and control individuals showed enhanced MNCM− scores in the medical radiation workers group (P=0.15). The highest MNCM− scores were obtained in the interventional radiologists/cardiologists group, and these scores were significantly higher compared with those obtained from the matched control group (P=0.05). The higher MNCM− scores observed in interventional radiologists/cardiologists compared with nuclear medicine technicians were not in agreement with the personal dosimetry records in both groups, which may point to the limitation of 'double dosimetry' procedures used in interventional radiology/cardiology. In conclusion, the data obtained in the present study supports the importance of cytogenetic analysis, in addition to physical dosimetry, as a routine biomonitoring method in medical radiation workers receiving the

  18. Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction.

    PubMed

    Garg, Monika; Khanna, Deepa; Kalra, Sanjeev; Balakumar, Pitchai

    2016-10-01

    Fenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses. PMID:27148865

  19. Effect of very low doses of gamma radiation on motility of gill ciliated epithelia of Mytilus edulis.

    PubMed

    Karpenko, A A; Ivanovsky YuA

    1993-01-01

    An investigation of the effect of gamma radiation on the motility of mussel gill ciliated epithelia was conducted using dose rates of 0.9 and 2 mGy/h. There was a definite decrease in the beat frequency and a distortion of the metachronal wave by 20-30 min after irradiation with 0.9 Gy/h. With a total dose of 0.9 mGy, the beat frequency was decreased 2- to 2.5-fold. In the period after irradiation a restoration of the metachronal wave was observed, but the beat frequency was about 50% of the control level. Gamma irradiation completely stopped the beating of the cilia when given at a dose rate of 2 mGy/h.

  20. Analysis of the common deletions in the mitochondrial DNA is a sensitive biomarker detecting direct and non-targeted cellular effects of low dose ionizing radiation.

    PubMed

    Schilling-Tóth, Boglárka; Sándor, Nikolett; Kis, Eniko; Kadhim, Munira; Sáfrány, Géza; Hegyesi, Hargita

    2011-11-01

    One of the key issues of current radiation research is the biological effect of low doses. Unfortunately, low dose science is hampered by the unavailability of easily performable, reliable and sensitive quantitative biomarkers suitable detecting low frequency alterations in irradiated cells. We applied a quantitative real time polymerase chain reaction (qRT-PCR) based protocol detecting common deletions (CD) in the mitochondrial genome to assess direct and non-targeted effects of radiation in human fibroblasts. In directly irradiated (IR) cells CD increased with dose and was higher in radiosensitive cells. Investigating conditioned medium-mediated bystander effects we demonstrated that low and high (0.1 and 2Gy) doses induced similar levels of bystander responses and found individual differences in human fibroblasts. The bystander response was not related to the radiosensitivity of the cells. The importance of signal sending donor and signal receiving target cells was investigated by placing conditioned medium from a bystander response positive cell line (F11-hTERT) to bystander negative cells (S1-hTERT) and vice versa. The data indicated that signal sending cells are more important in the medium-mediated bystander effect than recipients. Finally, we followed long term effects in immortalized radiation sensitive (S1-hTERT) and normal (F11-hTERT) fibroblasts up to 63 days after IR. In F11-hTERT cells CD level was increased until 35 days after IR then reduced back to control level by day 49. In S1-hTERT cells the increased CD level was also normalized by day 42, however a second wave of increased CD incidence appeared by day 49 which was maintained up to day 63 after IR. This second CD wave might be the indication of radiation-induced instability in the mitochondrial genome of S1-hTERT cells. The data demonstrated that measuring CD in mtDNA by qRT-PCR is a reliable and sensitive biomarker to estimate radiation-induced direct and non-targeted effects.

  1. An Overview of the Regulation of Low Dose Radiation in the Nuclear and Non-nuclear Industries

    SciTech Connect

    Menon, Shankar; Valencia, Luis; Teunckens, Lucien

    2003-02-27

    Now that increasing numbers of nuclear power stations are reaching the end of their commercially useful lives, the management of the large quantities of very low level radioactive material that arises during their decommissioning has become a major subject of discussion, with very significant economic implications. Much of this material can, in an environmentally advantageous manner, be recycled for reuse without radiological restrictions. Much larger quantities--2-3 orders of magnitude larger--of material, radiologically similar to the candidate material for recycling from the nuclear industry, arise in non-nuclear industries like coal, fertilizer, oil and gas, mining, etc. In such industries, naturally occurring radioactivity is artificially concentrated in products, by-products or waste to form TENORM (Technologically Enhanced Naturally Occurring Radioactive Material). It is only in the last decade that the international community has become aware of the prevalence of TENORM, specially the activity levels and quantities arising in so many non-nuclear industries. The first reaction of international organizations seems to have been to propose different standards for the nuclear and non-nuclear industries, with very stringent release criteria for radioactive material from the regulated nuclear industry and up to thirty to a hundred times more liberal criteria for the release/exemption of TENORM from the as yet unregulated non-nuclear industries. There are significant strategic issues that need to be discussed and resolved. Some examples of these are: - Disposal aspects of long-lived nuclides, - The use of radioactive residues in building materials, - Commercial aspects of differing and discriminating criteria in competing power industries in a world of deregulated electric power production. Of even greater importance is the need for the discussion of certain basic issues, such as - The quantitative risk levels of exposure to ionizing radiation, - The need for in

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

    SciTech Connect

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

    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.

  3. Low-Dose Carcinogenicity Studies

    EPA Science Inventory

    One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

  4. Low-Dose Radiation Activates Akt and Nrf2 in the Kidney of Diabetic Mice: A Potential Mechanism to Prevent Diabetic Nephropathy

    PubMed Central

    Xing, Xiao; Zhang, Chi; Shao, Minglong; Tong, Qingyue; Zhang, Guirong; Li, Cai; Cheng, Jie; Jin, Shunzi; Ma, Jisheng; Wang, Guanjun; Li, Xiaokun; Cai, Lu

    2012-01-01

    Repetitive exposure of diabetic mice to low-dose radiation (LDR) at 25 mGy could significantly attenuate diabetes-induced renal inflammation, oxidative damage, remodeling, and dysfunction, for which, however, the underlying mechanism remained unknown. The present study explored the effects of LDR on the expression and function of Akt and Nrf2 in the kidney of diabetic mice. C57BL/6J mice were used to induce type 1 diabetes with multiple low-dose streptozotocin. Diabetic and age-matched control mice were irradiated with whole body X-rays at either single 25 mGy and 75 mGy or accumulated 75 mGy (25 mGy daily for 3 days) and then sacrificed at 1–12 h for examining renal Akt phosphorylation and Nrf2 expression and function. We found that 75 mGy of X-rays can stimulate Akt signaling pathway and upregulate Nrf2 expression and function in diabetic kidneys; single exposure of 25 mGy did not, but three exposures to 25 mGy of X-rays could offer a similar effect as single exposure to 75 mGy on the stimulation of Akt phosphorylation and the upregulation of Nrf2 expression and transcription function. These results suggest that single 75 mGy or multiple 25 mGy of X-rays can stimulate Akt phosphorylation and upregulate Nrf2 expression and function, which may explain the prevention of LDR against the diabetic nephropathy mentioned above. PMID:23227273

  5. N-Acetyl cysteine does not prevent liver toxicity from chronic low-dose plus subacute high-dose paracetamol exposure in young or old mice.

    PubMed

    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

    2016-06-01

    Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute overexposures. The risk of hepatotoxicity from nonacute 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 nonacute 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 subacute paracetamol overexposure, 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 (1.33 g/kg food) or control diet for 6 weeks. Mice were then dosed orally eight times over 3 days with additional paracetamol (250 mg/kg) or saline, followed by either one or two doses of oral NAC (1200 mg/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. Subacute 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 subacute 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 subacute paracetamol toxicity. PMID:26821200

  6. ROS/Autophagy/Nrf2 Pathway Mediated Low-Dose Radiation Induced Radio-Resistance in Human Lung Adenocarcinoma A549 Cell.

    PubMed

    Chen, Ni; Wu, Lijun; Yuan, Hang; Wang, Jun

    2015-01-01

    Low-dose ionizing radiation (LDIR) can induce radio-resistance to following high dose radiation in various mammalian cells. The protective role of LDIR has been thought to be associated with the overall outcomes of cancer radiotherapy. NF-E2 related factor 2 (Nrf2) is a transcription factor that plays pivotal roles in maintaining cellular oxidative equilibrium. Since oxidative stress has been indicated to be a mediator of LDIR induced radio-resistance, the role of Nrf2 in this process was investigated in this research. Our results showed that in human lung adenocarcinoma A549 cell, 5cGy alpha particle induced radio-resistance to following 75cGy alpha particle radiation. The expression level of Nrf2 and its target Heme Oxygenase-1(HO-1) increased after 5cGy radiation. Both the shRNA of Nrf2 and the chemical inhibitor of HO-1 suppressed the induced radio-resistance, indicating the involvement of Nrf2 antioxidant pathway in this process. Further, we found 5cGy radiation stimulated autophagy process in A549. Inhibition of the autophagy process resulted in suppression of the radio-resistance and the induced expression of Nrf2 and HO-1. ROS scavenger N-acetyl-L-cysteine (NAC) blocked the autophagy process induced by 5cGy alpha particle, the upregulation of Nrf2 and HO-1, as well as the induced radio-resistance. In conclusion, ROS elevation caused by LDIR promoted Autophagy/Nrf2-HO-1 and conferred radio-resistance in A549.

  7. Low-dose oral prolonged-release oxycodone/naloxone for chronic pain in elderly patients with cognitive impairment: an efficacy–tolerability pilot study

    PubMed Central

    Petrò, Emiliano; Ruffini, Elena; Cappuccio, Melania; Guerini, Valeria; Belotti, Gloria; Fascendini, Sara; Licini, Cristina; Marcassa, Claudio

    2016-01-01

    Objective This pilot study evaluated the efficacy and safety of prolonged-release oxycodone/naloxone (OXN-PR) in older subjects with chronic pain and mild-to-moderate cognitive impairment. Methods This was a prospective, observational, open-label study of 45-day duration. Patients with moderate-to-severe chronic pain and naïve to strong opioids were recruited from nursing homes and Alzheimer’s disease centers. OXN-PR was initiated at low doses (5 mg od or bid) and increased to a maximum of 20 mg bid. The primary efficacy endpoint was a pain intensity reduction of ≥30% from baseline (T0) to 15 days after OXN-PR initiation, as assessed by a numerical rating scale or the Pain Assessment in Advanced Dementia scale. Other assessments included the Barthel activities of daily living index, Neuropsychiatric Inventory, Bowel Function Index, and adverse events. Results The analysis included 53 patients (mean age, 83.0 years; mean Mini-Mental State Examination score, 18.6) with severe pain (median Numerical Rating Scale/Pain Assessment in Advanced Dementia 6) and substantial impairment in daily functioning (mean Barthel index, 32.2). The primary endpoint was achieved by 92.4% of patients. OXN-PR significantly reduced mean pain intensity from baseline to study end (numerical rating scale, 6.6±1.0 vs 2.3±1.1, P<0.0001; Pain Assessment in Advanced Dementia, 6.9±1.6 vs 0.9±0.8, P<0.0001). Substantial improvements from T0 to T45 in daily functioning (mean Barthel index, 32.2±16.8 vs 53.7±23.9, P<0.0001) and neuropsychiatric symptoms (mean Neuropsychiatric Inventory, 25.5±27.3 vs 8.8±9.0, P<0.0001) were also reported. OXN-PR was well tolerated and did not worsen bowel function. Conclusion In this pilot study, OXN-PR was effective in improving pain and other symptoms associated with dementia, with a favorable safety and tolerability profile. Large-scale trials in people with dementia are needed to improve clinical guidance for the assessment and treatment of pain in

  8. 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.

    PubMed

    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.

  9. [Searching Radiation Countermeasures using the Model of Prolonged Irradiation of Mice with Low Dose Rate and Evaluation of Their Influence on Heat Shock Protein Genes Expression].

    PubMed

    Rozhdestvensky, L M; Mikhailov, V F; Schlyakova, T G; Shagirova, J M; Shchegoleva, R A; Raeva, N F; Lisina, N I; Shulenina, L V; Zorin, V V; Pchelka, A V; Trubitsina, K Y

    2015-01-01

    Different radiomodificators (cytokine betaleukine, antioxidant phenoxan, antigipoksant limontar and nucleoside riboxin) were investigated on mice for evaluating their radiation protective capacity against prolonged (21 h) exposure at a dose of 12.6 Gy at a low dose rate of 10 mGy/min. Bone marrow cellularity and endogenic CFUs were used as evaluation criteria 9 days after exposure. Simultaneously, expression of the heat shock proteins of 25, 70 and 90 kDa in unexposed mice bone marrow was studied 2, 24 and 48 h after injections. Betaleukine only had a positive significant effect in both tests in the variants of 50 mcg/kg and 3 mcg/kg when administered 2 h and 22 h before exposure, correspondingly. Effects of betaleukine HSPs on expression were both stimulating and inhibiting, that was in contradiction with a constant positive effect in 5 experiments on exposed mice for each betaleukine variant. It argues against the vital role of HSPs in the betaleukine antiradiation effect. In 2 experiments with high temperatures betaleukine administered at a dose of 50 mcg/kg evoked a very high HSP-70 gene expression after 24 h, and mice exposed to irradiation at that time in a parallel experiment showed an increased radiation effect. It corresponds to the idea that HSPs serve a stress indicator.

  10. Effects of Melissa officinalis L. on oxidative status and DNA damage in subjects exposed to long-term low-dose ionizing radiation.

    PubMed

    Zeraatpishe, Akbar; Oryan, Shahrbano; Bagheri, Mohammad Hadi; Pilevarian, Ali Asghar; Malekirad, Ali Akbar; Baeeri, Maryam; Abdollahi, Mohammad

    2011-04-01

    The aim of this study was to determine the capability of Melissa officinalis L. (Lemon balm) infusion on improvement of oxidative stress status in radiology staff that were exposed to persistent low-dose radiation during work. The study was a before-after clinical trial performed on 55 radiology staff. They were asked to drink Lemon balm infusion which was prepared like a tea bag twice daily (1.5 g/100 mL) for 30 days. In the plasma, lipid peroxidation, DNA damage, catalase, superoxide dismutase, myeloperoxidase, and glutathione peroxidase activity were measured before and after using Lemon balm infusion.Use of Lemon balm infusion in radiology unit workers resulted in a significant improvement in plasma levels of catalase, superoxide dismutase, and glutathione peroxidase and a marked reduction in plasma DNA damage, myeloperoxidase, and lipid peroxidation. It is concluded that infusion of Lemon balm markedly improve oxidative stress condition and DNA damage in radiology staff when used as a dietary supplement for radiation protection. PMID:20858648

  11. Evaluation of three somatic genetic biomarkers as indicators of low dose radiation effects in clean-up workers of the Chernobyl nuclear reactor accident.

    PubMed

    Jones, I M; Tucker, J D; Langlois, R G; Mendelsohn, M L; Pleshanov, P; Nelson, D O

    2001-01-01

    The goals of this study were to assess three biomarkers of genetic effect for their individual and collective ability to detect and estimate radiation exposure in Russian Chernobyl clean-up workers. Work assignments were planned to limit dose to 0.25 Gy. The three biomarkers employed were chromosome translocations detectcd in lynmphocytes by florescence in situ hybridisation (FISH), and mutation at two genes, glycophorin A (GPA) in red blood cells detected by flow cytometry and hypoxanthine phosphoribosyltransferase (HPRT) in lymphocytes detected by selective cell culture. Samples were Obtained from 1992 to 2000. The time between exposure at Chernobyl and sample acquisition was > or =5 years. The lymphocyte assays detected an elevation over controls in average outcomes it clean-up workers: translocation rates were 46% higher when adjusted for age and smoking and HPRT mutant frequencies were were 16% higher when adjusted for age. The G PA assay did not detect an exposure effect. The results indicate that measuring frequency of translocations by FISH is preferred for low dose radiation, retrospective biochemistry.

  12. Effects of Melissa officinalis L. on oxidative status and DNA damage in subjects exposed to long-term low-dose ionizing radiation.

    PubMed

    Zeraatpishe, Akbar; Oryan, Shahrbano; Bagheri, Mohammad Hadi; Pilevarian, Ali Asghar; Malekirad, Ali Akbar; Baeeri, Maryam; Abdollahi, Mohammad

    2011-04-01

    The aim of this study was to determine the capability of Melissa officinalis L. (Lemon balm) infusion on improvement of oxidative stress status in radiology staff that were exposed to persistent low-dose radiation during work. The study was a before-after clinical trial performed on 55 radiology staff. They were asked to drink Lemon balm infusion which was prepared like a tea bag twice daily (1.5 g/100 mL) for 30 days. In the plasma, lipid peroxidation, DNA damage, catalase, superoxide dismutase, myeloperoxidase, and glutathione peroxidase activity were measured before and after using Lemon balm infusion.Use of Lemon balm infusion in radiology unit workers resulted in a significant improvement in plasma levels of catalase, superoxide dismutase, and glutathione peroxidase and a marked reduction in plasma DNA damage, myeloperoxidase, and lipid peroxidation. It is concluded that infusion of Lemon balm markedly improve oxidative stress condition and DNA damage in radiology staff when used as a dietary supplement for radiation protection.

  13. Real-time Molecular Study of Bystander Effects of Low dose Low LET radiation Using Living Cell Imaging and Nanoparticale Optics

    SciTech Connect

    Natarajan, Mohan; Xu, Nancy R; Mohan, Sumathy

    2013-06-03

    In this study two novel approaches are proposed to investigate precisely the low dose low LET radiation damage and its effect on bystander cells in real time. First, a flow shear model system, which would provide us a near in vivo situation where endothelial cells in the presence of extra cellular matrix experiencing continuous flow shear stress, will be used. Endothelial cells on matri-gel (simulated extra cellular matrix) will be subjected to physiological flow shear (that occurs in normal blood vessels). Second, a unique tool (Single nano particle/single live cell/single molecule microscopy and spectroscopy; Figure A) will be used to track the molecular trafficking by single live cell imaging. Single molecule chemical microscopy allows one to single out and study rare events that otherwise might be lost in assembled average measurement, and monitor many target single molecules simultaneously in real-time. Multi color single novel metal nanoparticle probes allow one to prepare multicolor probes (Figure B) to monitor many single components (events) simultaneously and perform multi-complex analysis in real-time. These nano-particles resist to photo bleaching and hence serve as probes for unlimited timeframe of analysis. Single live cell microscopy allows one to image many single cells simultaneously in real-time. With the combination of these unique tools, we will be able to study under near-physiological conditions the cellular and sub-cellular responses (even subtle changes at one molecule level) to low and very low doses of low LET radiation in real time (milli-second or nano-second) at sub-10 nanometer spatial resolution. This would allow us to precisely identify, at least in part, the molecular mediators that are responsible of radiation damage in the irradiated cells and the mediators that are responsible for initiating the signaling in the neighboring cells. Endothelial cells subjected to flow shear (2 dynes/cm2 or 16 dynes/cm2) and exposed to 0.1, 1 and 10

  14. Prospective study of daily low-dose nedaplatin and continuous 5-fluorouracil infusion combined with radiation for the treatment of esophageal squamous cell carcinoma

    PubMed Central

    2009-01-01

    Background Protracted low-dose concurrent chemotherapy combined with radiation has been proposed for enhanced treatment results for esophageal cancer. We evaluated the efficacy and the toxicity of a novel regimen of daily low-dose nedaplatin (cis-diammine-glycolatoplatinum) and continuous infusion of 5-fluorouracil (5-FU) with radiation in patients with esophageal squamous cell carcinoma. Methods Between January 2003 and June 2008, 33 patients with clinical stage I to IVB esophageal squamous cell carcinoma were enrolled. Nedaplatin (10 mg/body/day) was administered daily and 5-FU (500 mg/body/day) was administered continuously for 20 days. Fractionated radiotherapy for a total dose of 50.4-66 Gy was administered together with chemotherapy. Additional chemotherapy with nedaplatin and 5-FU was optionally performed for a maximum of 5 courses after chemoradiotherapy. The primary end-point of this study was to evaluate the tumor response, and the secondary end-points were to evaluate the toxicity and the overall survival. Results Twenty-two patients (72.7%) completed the regimen of chemoradiotherapy. Twenty patients (60.6%) achieved a complete response, 10 patients (30.3%) a partial response. One patient (3.0%) had a stable disease, and 2 (6.1%) a progressive disease. The overall response rate was 90.9% (95% confidence interval: 75.7%-98.1%). For grade 3-4 toxicity, leukopenia was observed in 75.8% of the cases, thrombocytopenia in 24.2%, anemia in 9.1%, and esophagitis in 36.4%, while late grade 3-4 cardiac toxicity occurred in 6.1%. Additional chemotherapy was performed for 26 patients (78.8%) and the median number of courses was 3 (range, 1-5). The 1-, 2- and 3-year survival rates were 83.9%, 76.0% and 58.8%, respectively. The 1- and 2-year survival rates were 94.7% and 88.4% in patients with T1-3 M0 disease, and 66.2% and 55.2% in patients with T4/M1 disease. Conclusion The treatment used in our study may yield a high complete response rate and better survival for

  15. Skin cancer in patients with chronic radiation dermatitis

    SciTech Connect

    Davis, M.M.; Hanke, C.W.; Zollinger, T.W.; Montebello, J.F.; Hornback, N.B.; Norins, A.L.

    1989-04-01

    The cases of 76 patients with chronic radiation dermatitis resulting from low-dose ionizing radiation for benign disease were reviewed retrospectively for risk factors leading to the development of neoplasia. The patients were studied with respect to original hair color, eye color, sun reactive skin type, benign disease treated, area treated, age at treatment, and age at development of first skin cancer. Analysis of data showed 37% of patients had sun-reactive skin type I, 27% had type II, and 36% had type III. Types IV through VI were not represented. There appeared to be an overrepresentation of types I and II. Increased melanin pigmentation may therefore be either directly or indirectly protective against the development of skin cancers in patients who have received low-dose superficial ionizing radiation for benign disease. The sun-reactive skin type of patients with chronic radiation dermatitis may be used as a predictor of skin cancer risk when the total dose of ionizing radiation is not known.

  16. Low-dose ionizing radiation induces direct activation of natural killer cells and provides a novel approach for adoptive cellular immunotherapy.

    PubMed

    Yang, Guozi; Kong, Qingyu; Wang, Guanjun; Jin, Haofan; Zhou, Lei; Yu, Dehai; Niu, Chao; Han, Wei; Li, Wei; Cui, Jiuwei

    2014-12-01

    Recent evidence indicates that limited availability and cytotoxicity have restricted the development of natural killer (NK) cells in adoptive cellular immunotherapy (ACI). While it has been reported that low-dose ionizing radiation (LDIR) could enhance the immune response in animal studies, the influence of LDIR at the cellular level has been less well defined. In this study, the authors aim to investigate the direct effects of LDIR on NK cells and the potential mechanism, and explore the application of activation and expansion of NK cells by LDIR in ACI. The authors found that expansion and cytotoxicity of NK cells were markedly augmented by LDIR. The levels of IFN-γ and TNF-α in the supernatants of cultured NK cells were significantly increased after LDIR. Additionally, the effect of the P38 inhibitor (SB203580) significantly decreased the expanded NK cell cytotoxicity, cytokine levels, and expression levels of FasL and perforin. These findings indicate that LDIR induces a direct expansion and activation of NK cells through possibly the P38-MAPK pathway, which provides a potential mechanism for stimulation of NK cells by LDIR and a novel but simplified approach for ACI.

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

    PubMed Central

    Mendes, Adélia; Costa, Natália Rios; Chora, Inês; Ferreira, Sara; Araújo, Emanuel; Lopes, Pedro; Rosa, Gilberto; Marques, Pedro; Bettencourt, Paulo; Oliveira, Inês; Costa, Francisco; Ramos, Isabel; Teles, Maria José; Guimarães, João Tiago; Sobrinho-Simões, Manuel; Soares, Paula

    2016-01-01

    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. PMID:27662210

  18. Low-Dose Radiation-Induced Enhancement of Thymic Lymphomagenesis in Lck-Bax Mice is Dependent on LET and Gender

    PubMed Central

    Jacobus, James A.; Duda, Chester G.; Coleman, Mitchell C.; Martin, Sean M.; Mapuskar, Kranti; Mao, Gaowei; Smith, Brian J.; Aykin-Burns, Nukhet; Guida, Peter; Gius, David; Domann, Frederick E.; Knudson, C. Michael; Spitz, Douglas R.

    2013-01-01

    The hypothesis that mitochondrial dysfunction and increased superoxide levels in thymocytes over expressing Bax (Lck-Bax1 and Lck-Bax38&1) contributes to lymphomagenesis after low-dose radiation was tested. Lck-Bax1 single-transgenic and Lck-Bax38&1 double-transgenic mice were exposed to single whole-body doses of 10 or 100 cGy of 137Cs or iron ions (1,000 MeV/n, 150 keV/μm) or silicon ions (300 MeV/n, 67 keV/μm). A 10 cGy dose of 137Cs significantly increased the incidence and onset of thymic lymphomas in female Lck-Bax1 mice. In Lck-Bax38&1 mice, a 100 cGy dose of high-LET iron ions caused a significant dose dependent acceleration of lymphomagenesis in both males and females that was not seen with silicon ions. To determine the contribution of mitochondrial oxidative metabolism, Lck-Bax38&1 over expressing mice were crossed with knockouts of the mitochondrial protein deacetylase, Sirtuin 3 (Sirt3), which regulates superoxide metabolism. Sirt3−/−/Lck-Bax38&1 mice demonstrated significant increases in thymocyte superoxide levels and acceleration of lymphomagenesis (P < 0.001). These results show that lymphomagenesis in Bax over expressing animals is enhanced by radiation exposure in both an LET and gender dependent fashion. These findings support the hypothesis that mitochondrial dysfunction leads to increased superoxide levels and accelerates lymphomagenesis in Lck-Bax transgenic mice. PMID:23819597

  19. The Impact of Adaptive and Non-targeted Effects in the Biological Responses to Low Dose/Low Fluence Ionizing-Radiation: The Modulating Effect of Linear Energy Transfer

    PubMed Central

    de Toledo, Sonia M.; Buonanno, Manuela; Li, Min; Asaad, Nesrin; Qin, Yong; Zhang, Jie; Azzam, Edouard I.

    2011-01-01

    A large volume of laboratory and human epidemiological studies have shown that high doses of ionizing radiation engender significant health risks. In contrast, the health risks of low level radiation remain ambiguous and have been the subject of intense debate. To reduce the uncertainty in evaluating these risks, research advances in cellular and molecular biology are being used to characterize the biological effects of low dose radiation exposures and their underlying mechanisms. Radiation type, dose rate, genetic susceptibility, cellular redox environment, stage of cell growth, level of biological organization and environmental parameters are among the factors that modulate interactions among signaling processes that determine short- and long-term outcomes of low dose exposures. Whereas, recommended radiation protection guidelines assume a linear dose-response relationship in estimating radiation cancer risk, in vitro and in vivo investigations of phenomena such as adaptive responses and non-targeted effects, namely bystander effects and genomic instability, suggest that low dose/low fluence-induced signaling events act to alter linearity of the dose-response relation as supported by the biophysical argument. The latter predicts that increases in dose simply increase the probability that a given cell in a tissue will be intersected by an electron track, and by corollary, each unit of radiation, no matter how small would increases risk. These predictions assume that similar molecular events mediate both low and high dose radiobiological effects, and the cumulative risk from two sequential radiation exposures can never be less than one alone. PMID:21512606

  20. Exposure to Low-Dose 56Fe-Ion Radiation Induces Long-Term Epigenetic Alterations in Mouse Bone Marrow Hematopoietic Progenitor and Stem Cells

    PubMed Central

    Chang, Jianhui; Feng, Wei; Wang, Yingying; Allen, Antiño R.; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Zhou, Daohong

    2014-01-01

    There is an increasing need to better understand the long-term health effects of high-linear energy transfer (LET) radiation due to exposure during space missions, as well as its increasing use in clinical treatments. Previous studies have indicated that exposure to 56Fe heavy ions increases the incidence of acute myeloid leukemia (AML) in mice but the underlying molecular mechanisms remain elusive. Epigenetic alterations play a role in radiation-induced genomic instability and the initiation and progression of AML. In this study, we assessed the effects of low-dose 56Fe-ion irradiation on epigenetic alterations in bone marrow mononuclear cells (BM-MNCs) and hematopoietic progenitor and stem cells (HPSCs). Exposure to 56Fe ions (600 MeV, 0.1, 0.2 and 0.4 Gy) resulted in significant epigenetic alterations involving methylation of DNA, the DNA methylation machinery and expression of repetitive elements. Four weeks after irradiation, these changes were primarily confined to HPSCs and were exhibited as dose-dependent hypermethylation of LINE1 and SINE B1 repetitive elements [4.2-fold increase in LINE1 (P < 0.001) and 7.6-fold increase in SINE B1 (P < 0.01) after exposure to 0.4 Gy; n = 5]. Epigenetic alterations were persistent and detectable for at least 22 weeks after exposure, when significant loss of global DNA hypomethylation (1.9-fold, P < 0.05), decreased expression of Dnmt1 (1.9-fold, P < 0.01), and increased expression of LINE1 and SINE B1 repetitive elements (2.8-fold, P < 0.001 for LINE1 and 1.9-fold, P < 0.05 for SINE B1; n = 5) were observed after exposure to 0.4 Gy. In contrast, exposure to 56Fe ions did not result in accumulation of increased production of reactive oxygen species (ROS) and DNA damage, exhibited as DNA strand breaks. Furthermore, no significant alterations in cellular senescence and apoptosis were detected in HPSCs after exposure to 56Fe-ion radiation. These findings suggest that epigenetic reprogramming is possibly involved in the

  1. A report from the 2013 international symposium: the evaluation of the effects of low-dose radiation exposure in the life span study of atomic bomb survivors and other similar studies.

    PubMed

    Grant, E J; Ozasa, K; Ban, N; de González, A Berrington; Cologne, J; Cullings, H M; Doi, K; Furukawa, K; Imaoka, T; Kodama, K; Nakamura, N; Niwa, O; Preston, D L; Rajaraman, P; Sadakane, A; Saigusa, S; Sakata, R; Sobue, T; Sugiyama, H; Ullrich, R; Wakeford, R; Yasumura, S; Milder, C M; Shore, R E

    2015-05-01

    The RERF International Low-Dose Symposium was held on 5-6 December 2013 at the RERF campus in Hiroshima, Japan, to discuss the issues facing the Life Span Study (LSS) and other low-dose studies. Topics included the current status of low-dose risk detection, strategies for low-dose epidemiological and statistical research, methods to improve communication between epidemiologists and biologists, and the current status of radiological studies and tools. Key points made by the participants included the necessity of pooling materials over multiple studies to gain greater insight where data from single studies are insufficient; generating models that reflect epidemiological, statistical, and biological principles simultaneously; understanding confounders and effect modifiers in the current data; and taking into consideration less studied factors such as the impact of dose rate. It is the hope of all participants that this symposium be used as a trigger for further studies, especially those using pooled data, in order to reach a greater understanding of the health effects of low-dose radiation.

  2. A report from the 2013 international symposium: the evaluation of the effects of low-dose radiation exposure in the life span study of atomic bomb survivors and other similar studies.

    PubMed

    Grant, E J; Ozasa, K; Ban, N; de González, A Berrington; Cologne, J; Cullings, H M; Doi, K; Furukawa, K; Imaoka, T; Kodama, K; Nakamura, N; Niwa, O; Preston, D L; Rajaraman, P; Sadakane, A; Saigusa, S; Sakata, R; Sobue, T; Sugiyama, H; Ullrich, R; Wakeford, R; Yasumura, S; Milder, C M; Shore, R E

    2015-05-01

    The RERF International Low-Dose Symposium was held on 5-6 December 2013 at the RERF campus in Hiroshima, Japan, to discuss the issues facing the Life Span Study (LSS) and other low-dose studies. Topics included the current status of low-dose risk detection, strategies for low-dose epidemiological and statistical research, methods to improve communication between epidemiologists and biologists, and the current status of radiological studies and tools. Key points made by the participants included the necessity of pooling materials over multiple studies to gain greater insight where data from single studies are insufficient; generating models that reflect epidemiological, statistical, and biological principles simultaneously; understanding confounders and effect modifiers in the current data; and taking into consideration less studied factors such as the impact of dose rate. It is the hope of all participants that this symposium be used as a trigger for further studies, especially those using pooled data, in order to reach a greater understanding of the health effects of low-dose radiation. PMID:25811153

  3. Interaction of four low dose toxic metals with essential metals in brain, liver and kidneys of mice on sub-chronic exposure.

    PubMed

    Cobbina, Samuel Jerry; Chen, Yao; Zhou, Zhaoxiang; Wu, Xueshan; Feng, Weiwei; Wang, Wei; Li, Qian; Zhao, Ting; Mao, Guanghua; Wu, Xiangyang; Yang, Liuqing

    2015-01-01

    This study reports on interactions between low dose toxic and essential metals. Low dose Pb (0.01mg/L), Hg (0.001mg/L), Cd (0.005mg/L) and As (0.01mg/L) were administered singly to four groups of 3-week old mice for 120 days. Pb exposure increased brain Mg and Cu by 55.5% and 266%, respectively. Increased brain Mg resulted from metabolic activity of brain to combat insults, whiles Cu overload was due to alteration and dysfunction of CTR1 and ATP7A molecules. Reduction of liver Ca by 56.0% and 31.6% (on exposure to As and Cd, respectively) resulted from inhibition of Ca-dependent ATPase in nuclei and endoplasmic reticulum through binding with thiol groups. Decreased kidney Mg, Ca and Fe was due to uptake of complexes of As and Cd with thiol groups from proximal tubular lumen. At considerably low doses, the study establishes that, toxic metals disturb the homeostasis of essential metals.

  4. Comparison of cancer risk associated with low-dose ionizing radiation from cardiac imaging and therapeutic procedures after acute myocardial infarction in women versus men.

    PubMed

    Lawler, Patrick R; Afilalo, Jonathan; Eisenberg, Mark J; Pilote, Louise

    2013-11-15

    Patients with cardiovascular disease are increasingly exposed to low-dose ionizing radiation (LDIR) from diagnostic and therapeutic procedures. Previous studies have suggested that the malignancy risk associated with LDIR may be greatest in women and in young patients. We sought to compare the effect of LDIR on incident cancer across gender and age strata in a population-based cohort of patients with myocardial infarction (MI). All initially cancer-free patients with MI from 1996 to 2006 were identified in a province-wide administrative database. Procedure-specific LDIR dose estimates were used to generate a cumulative cardiac LDIR exposure variable. Time-dependent multivariate Cox regression was used to determine the relation between cardiac LDIR and incident cancer. A time-lag covariate of 3 years was used wherein a de novo cancer could only be attributed to LDIR incurred at least 3 years earlier. The effect of age and gender on LDIR-associated risk of cancer was evaluated with stratified models and the addition of interaction terms. The study cohort consisted of 56,606 men and 26,255 women. For each millisievert of cardiac LDIR, women were more likely to develop a cancer (hazard ratio 1.005, 95% confidence interval 1.002 to 1.008) than men (hazard ratio 1.002, 95% confidence interval 1.001 to 1.004) after adjusting for age, noncardiac LDIR, and covariates (p for interaction = 0.014). Contrarily, over the range studied (predominantly patients aged >50 years), age was not a determinant of LDIR-associated risk of cancer. In conclusion, women exposed to LDIR from cardiac imaging and therapeutic procedures after MI are at a greater risk of incident cancer compared with men after similar exposure. The extrapolated absolute risk from LDIR exposure would nonetheless be expected to be low.

  5. ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis

    ClinicalTrials.gov

    2014-07-14

    Chronic Kidney Disease; End Stage Renal Disease; Coronary Artery Calcification; Vascular Calcification; Calcification; Cardiovascular Disease; Chronic Renal Failure; Hyperparathyroidism; Kidney Disease; Nephrology; Secondary Hyperparathyroidism

  6. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    PubMed

    Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

    2016-05-01

    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

  7. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    PubMed

    Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

    2016-05-01

    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

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

    PubMed Central

    Busby, Christopher C.

    2009-01-01

    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. PMID:20049249

  9. Radiation cancer analysis and low dose risk estimation: new developments and perspectives - conference to be held Feb 2002. Final technical report for period November 1, 2001--October 31, 2002

    SciTech Connect

    Brugmans, M.J.P.; Leenhouts, H.P.

    2002-10-01

    The Proceedings of the 20th LH Gray Conference on Radiation Cancer Analysis and Low Dose Risk Estimation: New Developments and Perspectives (17-21 February 2002, Ede, the Netherlands) comprises 32 peer-reviewed papers on invited and proffered contributions to the conference with a preface by the guest editors. The on-going discussion of low dose radiation risk; the issue of the linear, non-threshold extrapolation; and the anticipated new recommendations, e.g. from BEIR and ICRP, provided the back-drop for the conference. The meeting dealt with topics such as basic mechanisms and bystander effects, cancer modeling, cancer genetics, radon exposure and lung cancer risk, cancer after medical exposure, cancer risk estimation, dose-effect relationships, and application to radiation protection.

  10. Low Dose Effects: Benefit or Harm?

    PubMed

    Woloschak, Gayle E

    2016-03-01

    This forum article discusses issues related to the effects of low dose radiation, an area that is under intense study but difficult to assess. Experiments with large-scale animal studies are included in this paper; these studies point to the need for international consortia to examine and balance the results of these large-scale studies and databases. PMID:26808889

  11. Randomized, Multicenter Trial on the Effect of Radiation Therapy on Plantar Fasciitis (Painful Heel Spur) Comparing a Standard Dose With a Very Low Dose: Mature Results After 12 Months' Follow-Up

    SciTech Connect

    Niewald, Marcus; Micke, Oliver; Graeber, Stefan; Schaefer, Vera; Scheid, Christine; Fleckenstein, Jochen; Licht, Norbert; Ruebe, Christian

    2012-11-15

    Purpose: To conduct a randomized trial of radiation therapy for painful heel spur, comparing a standard dose with a very low dose. Methods and Materials: Sixty-six patients were randomized to receive radiation therapy either with a total dose of 6.0 Gy applied in 6 fractions of 1.0 Gy twice weekly (standard dose) or with a total dose of 0.6 Gy applied in 6 fractions of 0.1 Gy twice weekly (low dose). In all patients lateral opposing 4- to 6-MV photon beams were used. The results were measured using a visual analogue scale, the Calcaneodynia score, and the SF12 health survey. The fundamental phase of the study ended after 3 months, and the follow-up was continued up to 1 year. Patients with insufficient pain relief after 3 months were offered reirradiation with the standard dosage at any time afterward. Results: Of 66 patients, 4 were excluded because of withdrawal of consent or screening failures. After 3 months the results in the standard arm were highly significantly superior compared with those in the low-dose arm (visual analogue scale, P=.001; Calcaneodynia score, P=.027; SF12, P=.045). The accrual of patients was stopped at this point. Further evaluation after 12 months' follow-up showed the following results: (1) highly significant fewer patients were reirradiated in the standard arm compared with the low-dose arm (P<.001); (2) the results of patients in the low-dose arm who were reirradiated were identical to those in the standard arm not reirradiated (reirradiation as a salvage therapy if the lower dose was ineffective); (3) patients experiencing a favorable result after 3 months showed this even after 12 months, and some results even improved further between 3 and 12 months. Conclusions: This study confirms the superior analgesic effect of radiation therapy with 6-Gy doses on painful heel spur even for a longer time period of at least 1 year.

  12. Relative Biologic Effects of Low-Dose-Rate {alpha}-Emitting {sup 227}Th-Rituximab and {beta}-Emitting {sup 90}Y-Tiuexetan-Ibritumomab Versus External Beam X-Radiation

    SciTech Connect

    Dahle, Jostein Bruland, Oyvind S.; Larsen, Roy H.

    2008-09-01

    Purpose: To determine the relative biologic effects (RBE) of {alpha}-particle radiation from {sup 227}Th-rituximab and of {beta}-radiation from {sup 90}Y-tiuexetan-ibritumomab (Zevalin) compared with external beam X-radiation in the Raji lymphoma xenograft model. Methods and Materials: Radioimmunoconjugates were administered intravenously in nude mice with Raji lymphoma xenografts at different levels of activity. Absorbed dose to tumor was estimated by separate biodistribution experiments for {sup 227}Th-rituximab and Zevalin. Tumor growth was measured two to three times per week after injection or X-radiation. Treatment-induced increase in growth delay to reach tumor volumes of 500 and 1,000 mm{sup 3}, respectively, was used as an end point. Results: The absorbed radiation dose-rate in tumor was slightly more than 0.1 Gy/d for the first week following injection of {sup 227}Th-rituximab, and thereafter gradually decreased to 0.03 Gy/d at 21 days after injection. For treatment with Zevalin the maximum dose-rate in tumor was achieved already 6 h after injection (0.2 Gy/d), and thereafter decreased to 0.01 Gy/d after 7 days. The relative biologic effect was between 2.5 and 7.2 for {sup 227}Th-rituximab and between 1 and 1.3 for Zevalin. Conclusions: Both at low doses and low-dose-rates, the {sup 227}Th-rituximab treatment was more effective per absorbed radiation dose unit than the two other treatments. The considerable effect at low doses suggests that the best way to administer low-dose-rates, {alpha}-emitting radioimmunoconjugates is via multiple injections.

  13. The effects of integrated treatment of UV light and low dose gamma radiation on Escherichia coli O157:H7 and Salmonella enterica on grape tomatoes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In recent years considerable numbers of foodborne disease outbreaks associated with produce were reported and specifically Tomatoes have been involved with a number of multi state outbreaks. The purpose of this study was to evaluate efficacy of integrated treatment of UVC and low dose Gamma radiatio...

  14. Absence of long-term behavioral effects after sub-chronic administration of low doses of methamidophos in male and female rats.

    PubMed

    Temerowski, M; van der Staay, F J

    2005-01-01

    Putative long-term learning and memory effects of low-dose exposure to the cholinesterase inhibitor organophosphate methamidophos (Tamaron) early in life were studied in two parallel studies in middle-aged rats. Methamidophos was administered via the drinking water to female and male Wistar rats using nominal concentrations of 0 (control), 0.5, 1.5 and 4.5 ppm active ingredient for 16 weeks. Animals were then maintained for a recovery period of about 14 months without treatment. They were tested in the standard and repeated acquisition version of the Morris water escape task in two series of tests starting 33 and 55 weeks after termination of the methamidophos treatment. Functional observations and motor activity measurements preceded each series of testing. Exposure to methamidophos was confirmed by measurement of brain cholinesterase (ChE-B) at the end of the 16 weeks of treatment in satellite animals. At 4.5 ppm a biologically relevant reduction in ChE-B activity was observed without clinical signs of intoxication (males: 66%, females: 64% of control activity). Mid- and low-dose exposure to methamidophos revealed ChE-B activity of 90% and 100% in males and 88% and 97% in females, respectively. General examinations of the animals during treatment revealed no clinical signs suggesting cholinergic stimulation. Functional observations and motor activity measurements exhibited no relevant differences between treatment groups and controls. Neither the performance in the standard Morris water escape task that predominantly measures spatial reference memory, nor in the repeated acquisition task in the Morris tank, which predominantly measures spatial working memory, was affected by treatment with methamidophos. A small number of statistically significant differences were noted in the mean performance level between treatment groups, or between treatment by sex groups in both versions of the Morris task. However, these findings appeared to be idiosyncratic for a

  15. Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.

    PubMed

    Zent, Clive S; Taylor, Ronald P; Lindorfer, Margaret A; Beum, Paul V; LaPlant, Betsy; Wu, Wenting; Call, Timothy G; Bowen, Deborah A; Conte, Michael J; Frederick, Lori A; Link, Brian K; Blackwell, Sue E; Veeramani, Suresh; Baig, Nisar A; Viswanatha, David S; Weiner, George J; Witzig, Thomas E

    2014-07-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analog refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a Phase II trial testing the efficacy and tolerability of a short-duration regimen combining pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to decrease the risk of treatment-associated infections and to limit the loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n = 36) or previously untreated with 17p13 deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional, and eight patients had purine analog refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy, with only five (13%) patients having treatment-limiting toxicity and no treatment-related deaths. Twenty-two (56%) patients responded to treatment, with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression-free survival was 7.2 months, time to next treatment was 9.1 months, and overall survival was 34.1 months. The majority of deaths (82%) were caused by progressive disease, including transformed diffuse large B-cell lymphoma (n = 6). Correlative studies showed that low-dose rituximab activates complement and natural killer cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low-dose high-frequency rituximab is a tolerable and effective therapy for CLL and that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. PMID:24723493

  16. Chronic radiation enteritis and malnutrition.

    PubMed

    Webb, Gwilym James; Brooke, Rachael; De Silva, Aminda Niroshan

    2013-07-01

    Radiation enteritis is defined as the loss of absorptive capacity of the intestine following irradiation, which is most commonly seen after radiotherapy for pelvic and abdominal malignancies. It is divided into acute and chronic forms and usually presents with diarrhea and malabsorption. Malnutrition is a common complication of chronic radiation enteritis (CRE). We reviewed the etiology, prevalence, symptoms, diagnosis and management of CRE and CRE with malnutrition in this article. Functional short bowel syndrome as a cause of malnutrition in CRE is also considered. The diagnostic work-up includes serum markers, endoscopy, cross-sectional imaging and the exclusion of alternative diagnoses such as recurrent malignancy. Management options of CRE include dietary manipulation, anti-motility agents, electrolyte correction, probiotics, parenteral nutrition, surgical resection and small bowel transplantation. Treatment may also be required for coexisting conditions including vitamin B12 deficiency, bile acid malabsorption and depression.

  17. Dose-effect relationships, epidemiological analysis and the derivation of low dose risk.

    PubMed

    Leenhouts, H P; Chadwick, K H

    2011-03-01

    This paper expands on our recent comments in a letter to this journal about the analysis of epidemiological studies and the determination of low dose RBE of low LET radiation (Chadwick and Leenhouts 2009 J. Radiol. Prot. 29 445-7). Using the assumption that radiation induced cancer arises from a somatic mutation (Chadwick and Leenhouts 2011 J. Radiol. Prot. 31 41-8) a model equation is derived to describe cancer induction as a function of dose. The model is described briefly, evidence is provided in support of it, and it is applied to a set of experimental animal data. The results are compared with a linear fit to the data as has often been done in epidemiological studies. The article presents arguments to support several related messages which are relevant to epidemiological analysis, the derivation of low dose risk and the weighting factor of sparsely ionising radiations. The messages are: (a) cancer incidence following acute exposure should, in principle, be fitted to a linear-quadratic curve with cell killing using all the data available; (b) the acute data are dominated by the quadratic component of dose; (c) the linear fit of any acute data will essentially be dependent on the quadratic component and will be unrelated to the effectiveness of the radiation at low doses; consequently, (d) the method used by ICRP to derive low dose risk from the atomic bomb survivor data means that it is unrelated to the effectiveness of the hard gamma radiation at low radiation doses; (e) the low dose risk value should, therefore, not be used as if it were representative for hard gamma rays to argue for an increased weighting factor for tritium and soft x-rays even though there are mechanistic reasons to expect this; (f) epidemiological studies of chronically exposed populations supported by appropriate cellular radiobiological studies have the best chance of revealing different RBE values for different sparsely ionising radiations. PMID:21346287

  18. Genomic Instability Induced by Low Dose Irradiation

    SciTech Connect

    Evans, Helen H. Sedwick, David W. Veigl, Martina L.

    2006-07-15

    The goal of this project was to determine if genomic instability could be initiated by poorly repaired DNA damage induced by low doses of ionizing radiation leading to a mutator phenotype. Human cells were irradiated, then transfected with an unirradiated reporter gene at various times AFTER exposure. The vector carried an inactive GFP gene that fluoresced when the gene was activated by a delayed mutation. Fluorescent cells were measured in the interval of 50 hours to four days after transfection. The results showed that delayed mutations occurred in these cells after exposure to relatively low doses (0.3-1.0 Gy) of low or high ionizing radiation, as well as after treatment with hyrodgen peroxide (30-100 micromolar). The occurrence was both dose and time dependent, often decreasing at higher doses and later times. No marked difference was observed between the response of mis-match repair-proficient and -deficient cell lines. Although the results were quite reproducible within single experiments, difficulties were observed from experiment to experiment. Different reagents and assays were tested, but no improvement resulted. We concluded that this method is not sufficiently robust or consisent to be useful in the assay of the induction of genomic instability by low doses of radiation, at least in these cell lines under our conditions.

  19. Quantification of damage due to low-dose radiation exposure in mice: construction and application of a biodosimetric model using mRNA indicators in circulating white blood cells

    PubMed Central

    Ishihara, Hiroshi; Tanaka, Izumi; Yakumaru, Haruko; Tanaka, Mika; Yokochi, Kazuko; Fukutsu, Kumiko; Tajima, Katsushi; Nishimura, Mayumi; Shimada, Yoshiya; Akashi, Makoto

    2016-01-01

    Biodosimetry, the measurement of radiation damage in a biologic sample, is a reliable tool for increasing the accuracy of dose estimation. Although established chromosome analyses are suitable for estimating the absorbed dose after high-dose irradiation, biodosimetric methodology to measure damage following low-dose exposure is underdeveloped. RNA analysis of circulating blood containing radiation-sensitive cells is a candidate biodosimetry method. Here we quantified RNA from a small amount of blood isolated from mice following low-dose body irradiation (<0.5 Gy) aimed at developing biodosimetric tools for situations that are difficult to study in humans. By focusing on radiation-sensitive undifferentiated cells in the blood based on Myc RNA expression, we quantified the relative levels of RNA for DNA damage-induced (DDI) genes, such as Bax, Bbc3 and Cdkn1a. The RNA ratios of DDI genes/Myc in the blood increased in a dose-dependent manner 4 h after whole-body irradiation at doses ranging from 0.1 to 0.5 Gy (air-kerma) of X-rays, regardless of whether the mice were in an active or resting state. The RNA ratios were significantly increased after 0.014 Gy (air-kerma) of single X-ray irradiation. The RNA ratios were directly proportional to the absorbed doses in water ranging from 0.1 to 0.5 Gy, based on gamma-irradiation from 137Cs. Four hours after continuous irradiation with gamma-rays or by internal contamination with a beta-emitter, the increased RNA ratios resembled those following single irradiation. These findings indicate that the RNA status can be utilized as a biodosimetric tool to estimate low-dose radiation when focusing on undifferentiated cells in blood. PMID:26589759

  20. [Indications for low-dose CT in the emergency setting].

    PubMed

    Poletti, Pierre-Alexandre; Andereggen, Elisabeth; Rutschmann, Olivier; de Perrot, Thomas; Caviezel, Alessandro; Platon, Alexandra

    2009-08-19

    CT delivers a large dose of radiation, especially in abdominal imaging. Recently, a low-dose abdominal CT protocol (low-dose CT) has been set-up in our institution. "Low-dose CT" is almost equivalent to a single standard abdominal radiograph in term of dose of radiation (about one sixth of those delivered by a standard CT). "Low-dose CT" is now used routinely in our emergency service in two main indications: patients with a suspicion of renal colic and those with right lower quadrant pain. It is obtained without intravenous contrast media. Oral contrast is given to patients with suspicion of appendicitis. "Low-dose CT" is used in the frame of well defined clinical algorithms, and does only replace standard CT when it can reach a comparable diagnostic quality.

  1. Granzyme B mediates both direct and indirect cleavage of extracellular matrix in skin after chronic low-dose ultraviolet light irradiation

    PubMed Central

    Parkinson, Leigh G; Toro, Ana; Zhao, Hongyan; Brown, Keddie; Tebbutt, Scott J; Granville, David J

    2015-01-01

    Extracellular matrix (ECM) degradation is a hallmark of many chronic inflammatory diseases that can lead to a loss of function, aging, and disease progression. Ultraviolet light (UV) irradiation from the sun is widely considered as the major cause of visible human skin aging, causing increased inflammation and enhanced ECM degradation. Granzyme B (GzmB), a serine protease that is expressed by a variety of cells, accumulates in the extracellular milieu during chronic inflammation and cleaves a number of ECM proteins. We hypothesized that GzmB contributes to ECM degradation in the skin after UV irradiation through both direct cleavage of ECM proteins and indirectly through the induction of other proteinases. Wild-type and GzmB-knockout mice were repeatedly exposed to minimal erythemal doses of solar-simulated UV irradiation for 20 weeks. GzmB expression was significantly increased in wild-type treated skin compared to nonirradiated controls, colocalizing to keratinocytes and to an increased mast cell population. GzmB deficiency significantly protected against the formation of wrinkles and the loss of dermal collagen density, which was related to the cleavage of decorin, an abundant proteoglycan involved in collagen fibrillogenesis and integrity. GzmB also cleaved fibronectin, and GzmB-mediated fibronectin fragments increased the expression of collagen-degrading matrix metalloproteinase-1 (MMP-1) in fibroblasts. Collectively, these findings indicate a significant role for GzmB in ECM degradation that may have implications in many age-related chronic inflammatory diseases. PMID:25495009

  2. Granzyme B mediates both direct and indirect cleavage of extracellular matrix in skin after chronic low-dose ultraviolet light irradiation.

    PubMed

    Parkinson, Leigh G; Toro, Ana; Zhao, Hongyan; Brown, Keddie; Tebbutt, Scott J; Granville, David J

    2015-02-01

    Extracellular matrix (ECM) degradation is a hallmark of many chronic inflammatory diseases that can lead to a loss of function, aging, and disease progression. Ultraviolet light (UV) irradiation from the sun is widely considered as the major cause of visible human skin aging, causing increased inflammation and enhanced ECM degradation. Granzyme B (GzmB), a serine protease that is expressed by a variety of cells, accumulates in the extracellular milieu during chronic inflammation and cleaves a number of ECM proteins. We hypothesized that GzmB contributes to ECM degradation in the skin after UV irradiation through both direct cleavage of ECM proteins and indirectly through the induction of other proteinases. Wild-type and GzmB-knockout mice were repeatedly exposed to minimal erythemal doses of solar-simulated UV irradiation for 20 weeks. GzmB expression was significantly increased in wild-type treated skin compared to nonirradiated controls, colocalizing to keratinocytes and to an increased mast cell population. GzmB deficiency significantly protected against the formation of wrinkles and the loss of dermal collagen density, which was related to the cleavage of decorin, an abundant proteoglycan involved in collagen fibrillogenesis and integrity. GzmB also cleaved fibronectin, and GzmB-mediated fibronectin fragments increased the expression of collagen-degrading matrix metalloproteinase-1 (MMP-1) in fibroblasts. Collectively, these findings indicate a significant role for GzmB in ECM degradation that may have implications in many age-related chronic inflammatory diseases.

  3. Inter-Relationship between Low-Dose Hyper-Radiosensitivity and Radiation-Induced Bystander Effects in the Human T98G Glioma and the Epithelial HaCaT Cell Line.

    PubMed

    Fernandez-Palomo, Cristian; Seymour, Colin; Mothersill, Carmel

    2016-02-01

    Over the past several years, investigations in both low-dose hyper-radiosensitivity and increased radioresistance have been a focus of radiation oncology and biology research, since both conditions occur primarily in tumor cell lines. There has been significant progress in elucidating their signaling pathways, however uncertainties exist when they are studied together with radiation-induced bystander effects. Therefore, the aim of this work was to further investigate this relationship using the T98G glioma and HaCaT cell lines. T98G glioma cells have demonstrated a strong transition from hyper-radiosensitivity to induced radioresistance, and HaCaT cells do not show low-dose hypersensitivity. Both cell lines were paired using a mix-and-match protocol, which involved growing nonirradiated cells in culture media from irradiated cells and covering all possible combinations between them. The end points analyzed were clonogenic cell survival and live calcium measurements through the cellular membrane. Our data demonstrated that T98G cells produced bystander signals that decreased the survival of both reporter T98G and HaCaT cells. The bystander effect occurred only when T98G cells were exposed to doses below 1 Gy, which was corroborated by the induction of calcium fluxes. However, when bystander signals originated from HaCaT cells, the survival fraction increased in reporter T98G cells while it decreased in HaCaT cells. Moreover, the corresponding calcium data showed no calcium fluxes in T98G cells, while HaCaT cells displayed a biphasic calcium profile. In conclusion, our findings indicate a possible link between low-dose hyper-radiosensitivity and bystander effects. This relationship varies depending on which cell line functions as the source of bystander signals. This further suggests that the bystander mechanisms are more complex than previously expected and caution should be taken when extrapolating bystander results across all cell lines and all radiation doses

  4. Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells.

    PubMed

    Thé, Torriceli Souza; Portella, Renata Siqueira; Guerreiro, Marcos Lázaro; Andrade, Sonia Gumes

    2013-09-01

    Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH) has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL) treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs) in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL) in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c) and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

  5. Low-dose fludarabine with or without darbepoetin alfa in patients with chronic lymphocytic leukemia and comorbidity: primary results of the CLL9 trial of the German CLL Study Group.

    PubMed

    Goede, Valentin; Busch, Raymonde; Bahlo, Jasmin; Chataline, Viktoria; Kremers, Stephan; Müller, Lothar; Reschke, Daniel; Schlag, Rudolf; Schmidt, Burkhard; Vehling-Kaiser, Ursula; Wedding, Ulrich; Stilgenbauer, Stefan; Hallek, Michael

    2016-01-01

    This study was planned as a phase 3 trial to investigate low-dose fludarabine with or without darbepoetin alfa in older patients with previously untreated or treated chronic lymphocytic leukemia (CLL) and comorbidity. Due to slow recruitment, the study was terminated prematurely after accrual of 97 patients who, on average, were 74 years old and had a cumulative illness rating scale (CIRS) total score of 5. We report toxicity and efficacy of the study treatment. Grade 3-5 neutropenia and infection were observed in 25% and 10% of patients, respectively. Response was seen in 73% (5% complete remissions). Median event-free and overall survival was 12.2 and 44.8 months, respectively. No differences in outcome were found for patients treated with versus without darbepoetin alfa. In subjects with progressive/recurrent CLL during or after study treatment, overall survival was similar for patients receiving chemotherapy versus chemoimmunotherapy as salvage treatment. PMID:26293380

  6. Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Pease, Ronald; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kriby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce; Little, Bradley; Salzman, James; Chaumont, Geraldine; Duperray, Herve; Ouellet, Al; Buchner, Stephen; LaBel, Kenneth

    2011-01-01

    We have presented results of ultra-low dose rate irradiations (< or = 10 mrad(Si)/s) for a variety of radiation hardened and commercial linear bipolar devices. We observed low dose rate enhancement factors exceeding 1.5 in several parts. The worst case of dose rate enhancement resulted in functional failures, which occurred after 10 and 60 krad(Si), for devices irradiated at 0.5 and 10 mrad(Si)/s, respectively. Devices fabricated with radiation hardened processes and designs also displayed dose rate enhancement at below 10 mrad(Si)/s. Furthermore, the data indicated that these devices have not reached the damage saturation point. Therefore the degradation will likely continue to increase with increasing total dose, and the low dose rate enhancement will further magnify. The cases presented here, in addition to previous examples, illustrate the significance and pervasiveness of low dose rate enhancement at dose rates lower than 10 mrad(Si). These results present further challenges for radiation hardness assurance of bipolar linear circuits, and raise the question of whether the current standard test dose rate is conservative enough to bound degradations due to ELDRS.

  7. Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice.

    PubMed

    Taylor, Kristina; Lemon, Jennifer A; Phan, Nghi; Boreham, Douglas R

    2014-07-01

    There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[(18)F] fluoro-2-deoxy-d-glucose ((18)F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancer risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy (18)F-FDG, 4 Gy γ-rays, 10 mGy (18)F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from (18)F-FDG, with respect to malignancy, is approximately 1. However; when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.

  8. Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice

    SciTech Connect

    Taylor, Kristina; Lemon, Jennifer A.; Phan, Nghi; Boreham, Douglas R.

    2014-05-28

    There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancer risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy 18F-FDG, 4 Gy γ-rays, 10 mGy 18F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from 18F-FDG, with respect to malignancy, is approximately 1. Furthermore, when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average

  9. Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice

    DOE PAGESBeta

    Taylor, Kristina; Lemon, Jennifer A.; Phan, Nghi; Boreham, Douglas R.

    2014-05-28

    There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancermore » risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy 18F-FDG, 4 Gy γ-rays, 10 mGy 18F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from 18F-FDG, with respect to malignancy, is approximately 1. Furthermore, when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.« less

  10. Effects of chronic dietary exposure to a low-dose of Malathion, Aroclor-1254 and 3-methylcholanthrene on three biomarkers in male mice.

    PubMed

    Hackenberger, B K; Jarić, Davorka; Hackenberger, Dubravka; Stepić, Sandra

    2010-12-01

    The aim of this research was to examine the applicability of some chronic toxicological tests in the determination of exposure to xenobiotics present in concentrations below No Observed Adverse Effect Level (NOAEL) and below the detection limit of analytical instruments. In the present experiment tested chemicals (Malathion, Aroclor-1254 and 3-methylcholanthrene (3-MC)) were mixed with wheat grains and given to male mice as feed over a period of 12 months. 7-ethoxyresorufin-O-deethylase (EROD) activity with the 3-MC and Aroclor-1254 treatments reached the peak at 9th month of exposure (26.7 and 42.4 pmol⁻¹ mg(prot)-⁻¹, respectively), while malathion did not have significant influence. Glutathione (GSH) level depletion was highest after three months of exposure. Unexpectedly, acetylcholinesterase (AChE) activity increased after treatment with malathion, an organophosphorous insecticide. In conclusion, low-level concentrations chronically administered exert certain effects on the levels of selected enzymes, e.g. biomarkers.

  11. Effects of chronic exposure to estradiol on ovarian cyclicity in C57BL/6J mice: potentiation at low doses and only partial suppression at high doses.

    PubMed

    Jesionowska, H; Karelus, K; Nelson, J F

    1990-08-01

    Long-term exposure to ovarian hormones contributes to age-related changes in estrous cyclicity in rodents. Estrogens are implicated in this process, but the concentration of estrogen required to exert these effects is not well established. Also, although estrogens are presumed to alter vaginal cyclicity by affecting the hypothalamic-pituitary axis, they may also impair the ability of the vaginal epithelium to cornify. To address these issues, young and middle-aged ovariectomized (ovx) C57BL/6J mice were exposed for 7-10 wk to plasma levels of estradiol (E2) at one of three ranges (30-40, 50-80, or 120-160 pg/ml). Ovaries from young mice were then transplanted under the renal capsule, and vaginal cyclicity was monitored for 4 mo. Mice exposed to the lowest level of E2 not only failed to stop cycling, but had a higher monthly frequency of estrous cycles than did controls (nearly 1 extra cycle/mo). Mice exposed to the intermediate level of E2 showed no impairment in cyclicity. Although mice exposed to the highest concentrations of E2 showed no vaginal cyclicity, they continued to ovulate as evidenced by fresh, albeit reduced, numbers of corpora lutea. These results indicate that, in ovx mice, (1) chronic exposure to relatively low concentrations of E2 potentiates cyclicity, (2) very high levels of E2 are required to induce acyclicity, and (3) this acyclicity reflects vaginal as well as neuroendocrine alterations. The results also indicate that vaginal acylicity may be a poor indicator of ovulatory acyclicity in mice that have been chronically exposed to E2.

  12. Switching to low-dose oral prolonged-release oxycodone/naloxone from WHO-Step I drugs in elderly patients with chronic pain at high risk of early opioid discontinuation

    PubMed Central

    Lazzari, Marzia; Marcassa, Claudio; Natoli, Silvia; Carpenedo, Roberta; Caldarulo, Clarissa; Silvi, Maria B; Dauri, Mario

    2016-01-01

    Purpose Chronic pain has a high prevalence in the aging population. Strong opioids also should be considered in older people for the treatment of moderate to severe pain or for pain that impairs functioning and the quality of life. This study aimed to assess the efficacy and safety of the direct switch to low-dose strong opioids (World Health Organization-Step III drugs) in elderly, opioid-naive patients. Patients and methods This was a single-center, retrospective, observational study in opioid-naive patients aged ≥75 years, with moderate to severe chronic pain (>6-month duration) and constipation, who initiated treatment with prolonged-release oxycodone/naloxone (OXN-PR). Patients were re-evaluated after 15, 30, and 60 days (T60, final observation). Response to treatment was defined as an improvement in pain of ≥30% after 30 days of therapy without worsening of constipation. Results One-hundred and eighty-six patients (mean ± SD age 80.7±4.7 years; 64.5% women) with severe chronic pain (mean average pain intensity 7.1±1.0 on the 11-point numerical rating scale) and constipation (mean Bowel Function Index 64.1±24.4; 89.2% of patients on laxatives) were initiated treatment with OXN-PR (mean daily dose 11.3±3.5 mg). OXN-PR reduced pain intensity rapidly and was well tolerated; 63.4% of patients responded to treatment with OXN-PR. At T60 (mean daily OXN-PR dose, 21.5±9.7 mg), the pain intensity was reduced by 66.7%. In addition, bowel function improved (mean decrease of Bowel Function Index from baseline to T60, −28.2, P<0.0001) and the use of laxatives decreased. Already after 15 days and throughout treatment, ~70% of patients perceived their status as much/extremely improved. Only 1.6% of patients discontinued treatment due to adverse events. Conclusion Low-dose OXN-PR in elderly patients naive to opioids proved to be an effective option for the treatment of moderate to severe chronic pain. Large-scale trials are needed to improve clinical guidance in

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

    SciTech Connect

    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

  14. A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG-ACRIN cancer research group (E1908).

    PubMed

    Zent, Clive S; Victoria Wang, Xin; Ketterling, Rhett P; Hanson, Curtis A; Libby, Edward N; Barrientos, Jacqueline C; Call, Timothy G; Chang, Julie E; Liu, Jane J; Calvo, Alejandro R; Lazarus, Hillard M; Rowe, Jacob M; Luger, Selina M; Litzow, Mark R; Tallman, Martin S

    2016-03-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients requiring initial therapy are often older and frailer and unsuitable candidates for standard chemoimmunotherapy regimens. Shorter duration combination monoclonal antibody (mAb) therapy using alemtuzumab and rituximab has been shown to be effective and tolerable treatment for CLL. Standard dose anti-CD20 mAb therapy causes loss of CD20 expression by surviving CLL cells, which can be minimized by decreasing the mAb dose. We report a randomized phase II clinical trial enrolling older (≥ 65 years) patients (median age 76 years, n = 31) with treatment naïve progressive CLL. Patients received 8-12 weeks of standard subcutaneous alemtuzumab with either intravenous standard (375 mg/m(2) weekly)(n = 16) or low dose (20 mg/m(2) 3x week)(n = 15) rituximab. This study was closed before full accrual because the manufacturer withdrew alemtuzumab for treatment of CLL. The overall response rate was 90% with an 45% complete response rate, median progression-free survival of 17.9 months and no significant differences in outcome between the low and standard dose rituximab arms. The major toxicities were cytopenia and infection with one treatment fatality caused by progressive multifocal leukoencephalopathy but no other opportunistic infections. Combination mAb therapy was effective and tolerable treatment for older and frailer patients with progressive CLL, achieving a high rate of complete remissions. These data support the role of mAb in therapy for less fit CLL patients and the further study of low dose higher frequency anti-CD20 mAb therapy as a potentially more effective use of anti-CD20 mAb in the treatment of CLL.

  15. [Influence of low-dose-rate red and near-infrared radiations on the level of reactive oxygen species, the genetic apparatus and the tumor growth in mice in vivo].

    PubMed

    2013-01-01

    The effect of low-dose-rate red and near-infrared radiations from the matrix of light emitted diode (650 nm and 850 nm) and a He-Ne laser (633 nm) on activation of the reserve of a natural defense system in the mice exposed to radiation in vivo was studied by the level of reactive oxygen species (ROS) production in blood cells, the induction of cytogenetic adaptive response in bone marrow cells, thymus and spleen, and the rate of Ehrlich ascites carcinoma growth in a solid form. As a positive control animals were irradiated with X-rays by the scheme of the radiation-induced adaptive response (0.1 Gy + 1.5 Gy). The levels of ROS production was assessed in whole blood by luminol-dependent chemiluminescence, of cytogenetic damage--by the "micronucleus test" in the bone marrow, the weight of the thymus and spleen--by index of organ, and the rate of tumor growth--according to its size for 30 days after inoculation. Adaptogenic and anticarcinogenic effects of studied radiations were revealed. The values of these effects were not different from those in animals pre-irradiated with the X-rays. The relationship between the level of ROS production and adaptive response induction in the mice under the influence of non-ionizing radiation was first ascertained. The experimental data obtained may indicate a similar mechanism of induction of protective responses to ionizing and non-ionizing radiations in mice in vivo.

  16. A semi‑automated FISH‑based micronucleus‑centromere assay for biomonitoring of hospital workers exposed to low doses of ionizing radiation.

    PubMed

    Vral, Anne; Decorte, Veerle; Depuydt, Julie; Wambersie, André; Thierens, Hubert

    2016-07-01

    The aim of the present study was to perform cytogenetic analysis by means of a semi‑automated micronucleus‑centromere assay in lymphocytes from medical radiation workers. Two groups of workers receiving the highest occupational doses were selected: 10 nuclear medicine technicians and 10 interventional radiologists/cardiologists. Centromere‑negative micronucleus (MNCM‑) data, obtained from these two groups of medical radiation workers were compared with those obtained in matched controls. The blood samples of the matched controls were additionally used to construct a 'low‑dose' (0‑100 mGy) MNCM‑ dose‑response curve to evaluate the sensitivity and suitability of the micronucleus‑centromere assay as an 'effect' biomarker in medical surveillance programs. The physical dosimetry data of the 3 years preceding the blood sampling, based on single or double dosimetry practices, were collected for the interpretation of the micronucleus data. The in vitro radiation results showed that for small sized groups, semi‑automated scoring of MNCM‑ enables the detection of a dose of 50 mGy. The comparison of MNCM‑ yields in medical radiation workers and control individuals showed enhanced MNCM‑ scores in the medical radiation workers group (P=0.15). The highest MNCM‑ scores were obtained in the interventional radiologists/cardiologists group, and these scores were significantly higher compared with those obtained from the matched control group (P=0.05). The higher MNCM‑ scores observed in interventional radiologists/cardiologists compared with nuclear medicine technicians were not in agreement with the personal dosimetry records in both groups, which may point to the limitation of 'double dosimetry' procedures used in interventional radiology/cardiology. In conclusion, the data obtained in the present study supports the importance of cytogenetic analysis, in addition to physical dosimetry, as a routine biomonitoring method in medical radiation

  17. Quantification of Adaptive Protection Following Low-dose Irradiation.

    PubMed

    Feinendegen, Ludwig E

    2016-03-01

    The question whether low doses and low dose-rates of ionizing radiation pose a health risk to people is of public, scientific and regulatory concern. It is a subject of intense debate and causes much fear. The controversy is to what extent low-dose effects, if any, cause or protect against damage such as cancer. Even if immediate molecular damage in exposed biological systems rises linearly with the number of energy deposition events (i.e., with absorbed dose), the response of the whole biological system to that damage is not linear. To understand how initial molecular damage affects a complex living system is the current challenge. PMID:26808882

  18. Breast cancer risk from low-dose exposures to ionizing radiation: results of parallel analysis of three exposed populations of women

    SciTech Connect

    Land, C.E.; Boice, J.D. Jr.; Shore, R.E.; Norman, J.E.; Tokunaga, M.

    1980-08-01

    Breast cancer incidence data were analyzed from three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis in Rochester, New York. Parallel analyses by radiation dose, age at exposure, and time after exposure suggested that risk of radiation-induced cancer increased approximately linearly with increasing dose and was heavily dependent on age at exposure; however, the risk was otherwise remarkably similar among the three populations, at least for ages 10 to 40 years at exposure, and followed the same temporal pattern of occurrence as did breast cancer incidence in nonexposed women of similar ages.

  19. mFISH analysis of irradiated human fibroblasts: a comparison among radiations with different quality in the low-dose range.

    PubMed

    Berardinelli, F; Nieri, D; Tanzarella, C; Cherubini, R; De Nadal, V; Gerardi, S; Sgura, A; Antoccia, A

    2015-09-01

    The present investigation aimed to characterise the shape of dose-response curve and determining the frequency distribution of various aberration types as a function of dose and radiation quality in AG01522 primary human fibroblasts in the 0.1- to 1-Gy dose range. For this purpose, the cells were irradiated with 7.7 and 28.5 keV µm(-1) low-energy protons, 62 keV µm(-1 4)He(2+) ions (LNL Radiobiology facility) or X rays and samples collected for 24-colour mFISH analysis. X rays and 7.7 keV µm(-1) protons displayed a quadratic dose-response curve solely for total and simple exchanges, whereas for high-linear energy transfer radiations, a linear dose-response curve was observed for all the aberration categories, with the exception of complex exchanges.

  20. mFISH analysis of irradiated human fibroblasts: a comparison among radiations with different quality in the low-dose range.

    PubMed

    Berardinelli, F; Nieri, D; Tanzarella, C; Cherubini, R; De Nadal, V; Gerardi, S; Sgura, A; Antoccia, A

    2015-09-01

    The present investigation aimed to characterise the shape of dose-response curve and determining the frequency distribution of various aberration types as a function of dose and radiation quality in AG01522 primary human fibroblasts in the 0.1- to 1-Gy dose range. For this purpose, the cells were irradiated with 7.7 and 28.5 keV µm(-1) low-energy protons, 62 keV µm(-1 4)He(2+) ions (LNL Radiobiology facility) or X rays and samples collected for 24-colour mFISH analysis. X rays and 7.7 keV µm(-1) protons displayed a quadratic dose-response curve solely for total and simple exchanges, whereas for high-linear energy transfer radiations, a linear dose-response curve was observed for all the aberration categories, with the exception of complex exchanges. PMID:25897136

  1. Cytotoxicity of Gold Nanoparticles with Varying Concentration and Under Low Dose Environmental Radiation on Human Embryonic Kidney 293 Cells (HEK-293)

    NASA Astrophysics Data System (ADS)

    Crudup, Shalana; Braender, Bruce; Iftode, Cristina; Dobbins, Tabbetha

    2013-03-01

    Nanomaterials are increasingly being used in medicine. Most research surrounding the health and safety effects of nanomaterials examine the cytotoxicity of nanoparticles alone. Few studies, as this one does, examines the combined effects of nanoparticle concentration and radiation exposure on cytotoxicity to human embryonic kidney 293 cells (HEK-293). Nanoparticles injected in the body are supposed to undergo biodegradation once they are done their specified task, however, some do not and accumulate in the cells (particularly at the liver and kidney) and this causes intracellular changes. Examples of intracellular changes are the disruption of organelle integrity or gene alterations. This will cause the cells to die because the cells are very sensitive to changes in their pH. The experiments reported here focus on the cytotoxicity of gold nanoparticles as a function of varying particle concentrations and also with and without exposure to UV radiation.

  2. Life-span exposure to sinusoidal-50 Hz magnetic field and acute low-dose γ radiation induce carcinogenic effects in Sprague-Dawley rats.

    PubMed

    Soffritti, Morando; Tibaldi, Eva; Padovani, Michela; Hoel, David G; Giuliani, Livio; Bua, Luciano; Lauriola, Michelina; Falcioni, Laura; Manservigi, Marco; Manservisi, Fabiana; Panzacchi, Simona; Belpoggi, Fiorella

    2016-01-01

    Background In 2002 the International Agency for Research on Cancer classified extremely low frequency magnetic fields (ELFMF) as a possible carcinogen on the basis of epidemiological evidence. Experimental bioassays on rats and mice performed up to now on ELFMF alone or in association with known carcinogens have failed to provide conclusive confirmation. Objectives To study the carcinogenic effects of combined exposure to sinusoidal-50 Hz (S-50 Hz) magnetic fields and acute γ radiation in Sprague-Dawley rats. Methods We studied groups of male and female Sprague-Dawley rats exposed from prenatal life until natural death to 20 or 1000 μT S-50 Hz MF and also to 0.1 Gy γ radiation delivered as a single acute exposure at 6 weeks of age. Results The results of the study showed significant carcinogenic effects for the mammary gland in males and females and a significant increased incidence of malignant schwannomas of the heart as well as increased incidence of lymphomas/leukemias in males. Conclusions These results call for a re-evaluation of the safety of non-ionizing radiation. PMID:26894944

  3. Nuclear apoJ: A low dose radiation inducible regulator of cell death. Final report for period September 15, 1998 - September 14, 2001

    SciTech Connect

    Aronow, Bruce J.

    2002-04-19

    gene targeting to increasing levels of ionizing radiation from a Cesium source. Data gathered under the support of this grant application initially indicated that apoJ deficient animals were more resistant to radiation, but as we accumulated more and more data points and covered a tighter exposure range, the genotype-based differences became insignificant. However, the possibility existed that because mortality based radiation-resistance could be attributable to mechanism for which nuclear apoJ was not rate determining, we maintained a very large of colony of apoJ knockout and wildtype animals in both the C57/B16 and Cv129 strain backgrounds that were exposed to sub-lethal levels of ionizing radiation to monitor for the occurrence of tumors. These animals were allowed to fully recover and age normally in either germ free or normal animal housing. Our results demonstrated no significant differences between wildtype and apoJ knockout animals over a period that extended up to 30 months for individual animals. We recorded similar weight gain, a relatively low mortality rate, and a similar mixture and rate of sarcoma and adenocarcinomas after surviving the initial ionizing radiation exposures. Thus we conclude that apoJ gene function, which was totally eliminated by our gene targeting, did not influence radiation sensitivity or serve as a tumor suppressor in response to DNA damage.

  4. Risk of Cataract after Exposure to Low Doses of Ionizing Radiation: A 20-Year Prospective Cohort Study among US Radiologic Technologists

    PubMed Central

    Bekiroglu, Nural; Hauptmann, Michael; Alexander, Bruce H.; Freedman, D. Michal; Doody, Michele Morin; Cheung, Li C.; Simon, Steven L.; Weinstock, Robert M.; Bouville, André; Sigurdson, Alice J.

    2008-01-01

    The study aim was to determine the risk of cataract among radiologic technologists with respect to occupational and nonoccupational exposures to ionizing radiation and to personal characteristics. A prospective cohort of 35,705 cataract-free US radiologic technologists aged 24–44 years was followed for nearly 20 years (1983–2004) by using two follow-up questionnaires. During the study period, 2,382 cataracts and 647 cataract extractions were reported. Cigarette smoking for ≥5 pack-years; body mass index of ≥25 kg/m2; and history of diabetes, hypertension, hypercholesterolemia, or arthritis at baseline were significantly (p ≤ 0.05) associated with increased risk of cataract. In multivariate models, self-report of ≥3 x-rays to the face/neck was associated with a hazard ratio of cataract of 1.25 (95% confidence interval: 1.06, 1.47). For workers in the highest category (mean, 60 mGy) versus lowest category (mean, 5 mGy) of occupational dose to the lens of the eye, the adjusted hazard ratio of cataract was 1.18 (95% confidence interval: 0.99, 1.40). Findings challenge the National Council on Radiation Protection and International Commission on Radiological Protection assumptions that the lowest cumulative ionizing radiation dose to the lens of the eye that can produce a progressive cataract is approximately 2 Gy, and they support the hypothesis that the lowest cataractogenic dose in humans is substantially less than previously thought. PMID:18664497

  5. Effects of Low-Dose and Long-Term Treatment with Erythromycin on Interleukin-17 and Interleukin-23 in Peripheral Blood and Induced Sputum in Patients with Stable Chronic Obstructive Pulmonary Disease

    PubMed Central

    Tan, Caimei; Huang, Huijuan; Zhang, Jianquan; He, Zhiyi; Zhong, Xiaoning; Bai, Jing

    2016-01-01

    Objective. To study the effects of low-dose and long-term treatment with erythromycin on IL-17 and IL-23, in peripheral blood and induced sputum, in patients with stable chronic obstructive pulmonary disease (COPD). Methods. Patients were randomly divided into placebo-treated group, group A (12 months of additive treatment with erythromycin, N = 18), and group B (6 months of additive treatment with erythromycin followed by 6 months of follow-up, N = 18). Inflammatory cells in induced sputum, pulmonary function, and the 6-minute walk distance (6MWD) were analyzed. Concentrations of IL-17 and IL-23 in peripheral blood and sputum were measured using enzyme-linked immunosorbent assays. Results. After treatment, sputum and peripheral blood concentrations of IL-17 and IL-23 significantly decreased in groups A and B compared with placebo-treated group. There were no significant differences after erythromycin withdrawal at months 9 and 12 in group B compared with placebo-treated group. An increase in 6MWD was observed after treatment. Conclusions. Erythromycin was beneficial and reduced airway inflammation in COPD patients. Underlying mechanisms may involve inhibition of IL-17 and IL-23 mediated airway inflammation. COPD patients treated with erythromycin for 6 months experienced improved exercise capacity. Finally, treatment for 12 months may be more effective than treatment for 6 months. PMID:27127346

  6. Neurobehavioral and cognitive performances of children exposed to low-dose radiation in the Chernobyl accident: the Israeli Chernobyl Health Effects Study.

    PubMed

    Bar Joseph, N; Reisfeld, D; Tirosh, E; Silman, Z; Rennert, G

    2004-09-01

    Exposure to low levels of ionizing radiation after the Chernobyl accident in the Ukraine could potentially have influenced the neurobehavioral and cognitive performances of exposed children. A cohort study of adolescents who were children at the time of the accident and who subsequently emigrated to Israel was conducted in 1998-2001. A total of 1,629 children (59% of all 2,769 invited) were included in the study (41% from higher contamination areas, 25% from lower contamination areas, 34% from noncontaminated areas). Mean scores of the Raven Standard Progressive Matrices Test were highest in children in all exposure groups whose parents had a high level of education. No overall relation was found between the cognitive function scores of the child and his/her putative radiation exposure level. Conners' test T scores did not differ significantly by level of exposure. Mothers of all exposure groups who were pregnant at the time of the accident gave their children significantly higher Conners' test scores than did those who were not pregnant. Scores for hyperactivity and attention-deficit/hyperactivity disorder were significantly higher among those who were in utero at the time of the accident. These results do not show differences of neurobehavioral or cognitive performance in exposed versus nonexposed children. There is a possible behavioral effect among offspring of pregnant mothers or mothers of very young children in all exposure levels.

  7. The effects of pre-emptive low-dose X-ray irradiation on MIA induced inflammatory pain in rats

    NASA Astrophysics Data System (ADS)

    Hahm, Suk-Chan; Lee, Go-Eun; Kim, Eun-Hye; Kim, Junesun; Lee, Taewoong; Lee, Wonho

    2013-07-01

    This study was performed to determine the effect of pre-emptive low-dose irradiation on the development of inflammatory pain and to characterize the potential mechanisms underlying this effect in osteoarthritis (OA) animal model. Whole-body X-irradiations with 0.1, 0.5, 1 Gy or sham irradiations were performed for 3 days before the induction of ostearthritis with monosodium iodoacetate (MIA) (40 µl, in saline) into the right knee joint in male Sprague Dawley rats. Behavioral tests for arthritic pain including evoked and non-evoked pain were conducted before and after MIA injection and inducible nitric-oxide synthase (iNOS) expression level was measured by western blot. Low-dose radiation significantly prevented the development of mechanical allodynia and thermal hyperalgesia and reduction in weight bearing that is regarded as a behavioral signs of non-evoked pain following MIA injection. Low-dose radiation significantly inhibited the increase in iNOS expression after MIA injection in spinal L3-5 segments in rat. These data suggest that low-dose X-irradiation is able to prevent the development of arthritic pain through modulation of iNOS expression in the spinal cord dorsal horn. Thus, low-dose radiotherapy could be substituted in part for treatment with drugs for patients with chronic inflammatory disease in clinical setting.

  8. Poly [1,1'-bis(ethynyl)-4,4'-biphenyl(bis-tributylphosphine)Pt(II)] solutions used as low dose ionizing radiation dosimeter

    NASA Astrophysics Data System (ADS)

    Bronze-Uhle, E. S.; Batagin-Neto, A.; Fernandes, D. M.; Fratoddi, I.; Russo, M. V.; Graeff, C. F. O.

    2013-06-01

    In this work, the effect of gamma radiation on the optical properties of polymetallayne poly[1,1'-bis(ethynyl)-4,4'-biphenyl(bis-tributylphosphine)Pt(II)] (Pt-DEBP) in chloroform solution is studied. The samples were irradiated at room temperature with doses from 0.01 Gy to 1 Gy using a 60Co gamma ray source. A new band at 420 nm is observed in the emission spectra, in superposition to the emission maximum at 398 nm, linearly dependent on dose. We propose to use the ratio of the emission amplitude bands as the dosimetric parameter. This method proved to be robust, accurate, and can be used as a dosimeter in medical applications.

  9. Poly [1,1'-bis(ethynyl)-4,4'-biphenyl(bis-tributylphosphine)Pt(II)] solutions used as low dose ionizing radiation dosimeter

    SciTech Connect

    Bronze-Uhle, E. S.; Graeff, C. F. O.; Batagin-Neto, A.; Fernandes, D. M.; Fratoddi, I.; Russo, M. V.

    2013-06-17

    In this work, the effect of gamma radiation on the optical properties of polymetallayne poly[1,1'-bis(ethynyl)-4,4'-biphenyl(bis-tributylphosphine)Pt(II)] (Pt-DEBP) in chloroform solution is studied. The samples were irradiated at room temperature with doses from 0.01 Gy to 1 Gy using a {sup 60}Co gamma ray source. A new band at 420 nm is observed in the emission spectra, in superposition to the emission maximum at 398 nm, linearly dependent on dose. We propose to use the ratio of the emission amplitude bands as the dosimetric parameter. This method proved to be robust, accurate, and can be used as a dosimeter in medical applications.

  10. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    SciTech Connect

    Engelward, Bevin P

    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

  11. Low-Dose Hyper-Radiosensitivity: Past, Present, and Future

    SciTech Connect

    Marples, Brian Collis, Spencer J.

    2008-04-01

    This review article discusses the biology of low-dose hyper-radiosensitivity (HRS) with reference to the molecular regulation of DNA repair and cell cycle control processes. Particular attention is paid to the significance of G2-phase cell cycle checkpoints in overcoming low-dose hyper-radiosensitivity and the impact of HRS on low-dose rate radiobiology. The history of HRS from the original in vivo discovery to the most recent in vitro and clinical data are examined to present a unifying hypothesis concerning the molecular control and regulation of this important low dose radiation response. Finally, preclinical and clinical data are discussed, from a molecular viewpoint, to provide theoretical approaches to exploit HRS biology for clinical gain.

  12. Low Dose Total Body Irradiation Combined With Recombinant CD19-Ligand × Soluble TRAIL Fusion Protein is Highly Effective Against Radiation-resistant B-precursor Acute Lymphoblastic Leukemia in Mice☆

    PubMed Central

    Uckun, Fatih M.; Myers, Dorothea E.; Ma, Hong; Rose, Rebecca; Qazi, Sanjive

    2015-01-01

    In high-risk remission B-precursor acute lymphoblastic leukemia (BPL) patients, relapse rates have remained high post-hematopoietic stem cell transplantation (HSCT) even after the use of very intensive total body irradiation (TBI)-based conditioning regimens, especially in patients with a high “minimal residual disease” (MRD) burden. New agents capable of killing radiation-resistant BPL cells and selectively augmenting their radiation sensitivity are therefore urgently needed. We report preclinical proof-of-principle that the potency of radiation therapy against BPL can be augmented by combining radiation with recombinant human CD19-Ligand × soluble TRAIL (“CD19L–sTRAIL”) fusion protein. CD19L–sTRAIL consistently killed radiation-resistant primary leukemia cells from BPL patients as well as BPL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. Low dose total body irradiation (TBI) combined with CD19L–sTRAIL was highly effective against (1) xenografted CD19+ radiochemotherapy-resistant human BPL in NOD/SCID (NS) mice challenged with an otherwise invariably fatal dose of xenograft cells derived from relapsed BPL patients as well as (2) radiation-resistant advanced stage CD19+ murine BPL with lymphomatous features in CD22ΔE12xBCR-ABL double transgenic mice. We hypothesize that the incorporation of CD19L–sTRAIL into the pre-transplant TBI regimens of patients with very high-risk BPL will improve their survival outcome after HSCT. PMID:26097891

  13. Low doses of ultraviolet radiation and oxidative damage induce dramatic accumulation of mitochondrial DNA replication intermediates, fork regression, and replication initiation shift.

    PubMed

    Torregrosa-Muñumer, Rubén; Goffart, Steffi; Haikonen, Juha A; Pohjoismäki, Jaakko L O

    2015-11-15

    Mitochondrial DNA is prone to damage by various intrinsic as well as environmental stressors. DNA damage can in turn cause problems for replication, resulting in replication stalling and double-strand breaks, which are suspected to be the leading cause of pathological mtDNA rearrangements. In this study, we exposed cells to subtle levels of oxidative stress or UV radiation and followed their effects on mtDNA maintenance. Although the damage did not influence mtDNA copy number, we detected a massive accumulation of RNA:DNA hybrid-containing replication intermediates, followed by an increase in cruciform DNA molecules, as well as in bidirectional replication initiation outside of the main replication origin, OH. Our results suggest that mitochondria maintain two different types of replication as an adaptation to different cellular environments; the RNA:DNA hybrid-involving replication mode maintains mtDNA integrity in tissues with low oxidative stress, and the potentially more error tolerant conventional strand-coupled replication operates when stress is high.

  14. Low dose exposure to sodium arsenite synergistically interacts with UV radiation to induce mutations and alter DNA repair in human cells.

    PubMed

    Danaee, Hadi; Nelson, Heather H; Liber, Howard; Little, John B; Kelsey, Karl T

    2004-03-01

    Inorganic arsenic is a known human carcinogen, yet its mechanism of action remains poorly understood. Epidemiological data suggest that arsenic exposure interacts with UV radiation exposure to increase the risk of skin cancer. Studies have suggested that arsenic is able to impair DNA repair enzymes and alter the repair of UV-induced DNA damage. Here we have tested the hypothesis that arsenite [As(III)] and UV interact synergistically to enhance mutagenesis. TK6 human lymphoblastoid cells that are functionally heterozygous at the thymidine kinase (TK) locus were pre-exposed to As(III) alone and in combination with UV. Our data suggest that As(III) is mutagenic only at high doses at the TK locus. As(III) enhanced UV mutagenesis in a more than additive fashion. To investigate the mechanism underlying this synergy we assessed the removal of UV-induced dimers in TK6 cells using the T4 endonuclease-incorporated Comet assay. Pre-treatment with As(III) specifically inhibited the repair of UV-induced pyrimidine dimer-related DNA damage. Taken together, these data suggest that pre-treatment of human cells with arsenic impairs the nucleotide excision repair pathway and leads to enhanced UV mutagenesis.

  15. Low Dose Suppression of Neoplastic Transformation in Vitro

    SciTech Connect

    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.

  16. Low dose neutron late effects: Cataractogenesis

    SciTech Connect

    Worgul, B.V.

    1991-12-01

    The work is formulated to resolve the uncertainty regarding the relative biological effectiveness (RBE) of low dose neutron radiation. The study exploits the fact that cataractogenesis is sensitive to the inverse dose-rate effect as has been observed with heavy ions and was an endpoint considered in the follow-up of the A-bomb survivors. The neutron radiations were initiated at the Radiological Research Accelerator facility (RARAF) of the Nevis Laboratory of Columbia University. Four week old ({plus minus} 1 day) rats were divided into eight dose groups each receiving single or fractionated total doses of 0.2, 1.0, 5.0 and 25.0 cGy of monoenergetic 435 KeV neutrons. Special restraining jigs insured that the eye, at the midpoint of the lens, received the appropriate energy and dose with a relative error of {plus minus}5%. The fractionation regimen consisted of four exposures, each administered at three hour ({plus minus}) intervals. The neutron irradiated groups are being compared to rats irradiated with 250kVp X-rays in doses ranging from 0.5 to 7 Gy. The animals are being examined on a biweekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit Lamp Imaging System (Zeiss). The follows-ups, entering their second year, will continue throughout the life-span of the animals. This is essential inasmuch as given the extremely low doses which are being utilized clinically detectable opacities were not anticipated until a significant fraction of the life span has lapsed. Current data support this contention. At this juncture cataracts in the irradiated groups are beginning to exceed control levels.

  17. Mitochondrial reactive oxygen species-mediated genomic instability in low-dose irradiated human cells through nuclear retention of cyclin D1.

    PubMed

    Shimura, Tsutomu; Kunugita, Naoki

    2016-06-01

    Mitochondria are associated with various radiation responses, including adaptive responses, mitophagy, the bystander effect, genomic instability, and apoptosis. We recently identified a unique radiation response in the mitochondria of human cells exposed to low-dose long-term fractionated radiation (FR). Such repeated radiation exposure inflicts chronic oxidative stresses on irradiated cells via the continuous release of mitochondrial reactive oxygen species (ROS) and decrease in cellular levels of the antioxidant glutathione. ROS-induced oxidative mitochondrial DNA (mtDNA) damage generates mutations upon DNA replication. Therefore, mtDNA mutation and dysfunction can be used as markers to assess the effects of low-dose radiation. In this study, we present an overview of the link between mitochondrial ROS and cell cycle perturbation associated with the genomic instability of low-dose irradiated cells. Excess mitochondrial ROS perturb AKT/cyclin D1 cell cycle signaling via oxidative inactivation of protein phosphatase 2A after low-dose long-term FR. The resulting abnormal nuclear accumulation of cyclin D1 induces genomic instability in low-dose irradiated cells. PMID:27078622

  18. Low-Dose Risk, Decisions, and Risk Communication

    SciTech Connect

    Flynn, James; Slovic, Paul

    2001-06-01

    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 & 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.

  19. Low-Dose Radiotherapy in Indolent Lymphoma

    SciTech Connect

    Rossier, Christine; Schick, Ulrike; Miralbell, Raymond; Mirimanoff, Rene O.; Weber, Damien C.; Ozsahin, Mahmut

    2011-11-01

    Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 months (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.

  20. Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis

    PubMed Central

    Chen, Jinmei; Hong, Jinsheng; Zou, Xi; Lv, Wenlong; Guo, Feibao; Hong, Hualan; Zhang, Weijian

    2015-01-01

    The aim of this study was to investigate the association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury (RILI) after intensity-modulated radiotherapy (IMRT) for lung cancer. The normal lung relative volumes receiving greater than 5, 10, 20 and 30 Gy (V5–30) mean lung dose (MLD), and absolute volumes spared from greater than 5, 10, 20 and 30 Gy (AVS5–30) for the bilateral and ipsilateral lungs of 83 patients were recorded. Any association of clinical factors and dose–volume parameters with Grade ≥2 RILI was analyzed. The median follow-up was 12.3 months; 18 (21.7%) cases of Grade 2 RILI, seven (8.4%) of Grade 3 and two (2.4%) of Grade 4 were observed. Univariate analysis revealed the located lobe of the primary tumor. V5, V10, V20, MLD of the ipsilateral lung, V5, V10, V20, V30 and MLD of the bilateral lung, and AVS5 and AVS10 of the ipsilateral lung were associated with Grade ≥2 RILI (P < 0.05). Multivariate analysis indicated AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI (P = 0.010, OR = 0.272, 95% CI: 0.102–0.729). Receiver operating characteristic curves indicated Grade ≥2 RILI could be predicted using AVS5 of the ipsilateral lung (area under curve, 0.668; cutoff value, 564.9 cm3; sensitivity, 60.7%; specificity, 70.4%). The incidence of Grade ≥2 RILI was significantly lower with AVS5 of the ipsilateral lung ≥564.9 cm3 than with AVS5 < 564.9 cm3 (P = 0.008). Low-dose irradiation relative volumes and MLD of the bilateral or ipsilateral lung were associated with Grade ≥2 RILI, and AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI for lung cancer after IMRT. PMID:26454068

  1. High-resolution low-dose scanning transmission electron microscopy

    PubMed Central

    Buban, James P.; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D.; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM. PMID:19915208

  2. High-resolution low-dose scanning transmission electron microscopy.

    PubMed

    Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

  3. Endoscopic management of chronic radiation proctitis

    PubMed Central

    Rustagi, Tarun; Mashimo, Hiroshi

    2011-01-01

    Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic radiotherapy. Although many cases resolve spontaneously, some lead to chronic symptoms including diarrhea, tenesmus, urgency and persistent rectal bleeding with iron deficiency anemia requiring blood transfusions. Treatments for chronic radiation proctitis remain unsatisfactory and the basis of evidence for various therapies is generally insufficient. There are very few controlled or prospective trials, and comparisons between therapies are limited because of different evaluation methods. Medical treatments, including formalin, topical sucralfate, 5-amino salicylic acid enemas, and short chain fatty acids have been used with limited success. Surgical management is associated with high morbidity and mortality. Endoscopic therapy using modalities such as the heater probe, neodymium:yttrium-aluminium-garnet laser, potassium titanyl phosphate laser and bipolar electrocoagulation has been reported to be of some benefit, but with frequent complications. Argon plasma coagulation is touted to be the preferred endoscopic therapy due to its efficacy and safety profile. Newer methods of endoscopic ablation such as radiofrequency ablation and cryotherapy have been recently described which may afford broader areas of treatment per application, with lower rate of complications. This review will focus on endoscopic ablation therapies, including such newer modalities, for chronic radiation proctitis. PMID:22147960

  4. Endoscopic management of chronic radiation proctitis.

    PubMed

    Rustagi, Tarun; Mashimo, Hiroshi

    2011-11-01

    Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic radiotherapy. Although many cases resolve spontaneously, some lead to chronic symptoms including diarrhea, tenesmus, urgency and persistent rectal bleeding with iron deficiency anemia requiring blood transfusions. Treatments for chronic radiation proctitis remain unsatisfactory and the basis of evidence for various therapies is generally insufficient. There are very few controlled or prospective trials, and comparisons between therapies are limited because of different evaluation methods. Medical treatments, including formalin, topical sucralfate, 5-amino salicylic acid enemas, and short chain fatty acids have been used with limited success. Surgical management is associated with high morbidity and mortality. Endoscopic therapy using modalities such as the heater probe, neodymium:yttrium-aluminium-garnet laser, potassium titanyl phosphate laser and bipolar electrocoagulation has been reported to be of some benefit, but with frequent complications. Argon plasma coagulation is touted to be the preferred endoscopic therapy due to its efficacy and safety profile. Newer methods of endoscopic ablation such as radiofrequency ablation and cryotherapy have been recently described which may afford broader areas of treatment per application, with lower rate of complications. This review will focus on endoscopic ablation therapies, including such newer modalities, for chronic radiation proctitis.

  5. Role of animal studies in low-dose extrapolation

    SciTech Connect

    Fry, R.J.M.

    1981-01-01

    Current data indicate that in the case of low-LET radiation linear, extrapolation from data obtained at high doses appears to overestimate the risk at low doses to a varying degree. In the case of high-LET radiation, extrapolation from data obtained at doses as low as 40 rad (0.4 Gy) is inappropriate and likely to result in an underestimate of the risk.

  6. The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.

    PubMed

    Yentrapalli, Ramesh; Azimzadeh, Omid; Sriharshan, Arundhathi; Malinowsky, Katharina; Merl, Juliane; Wojcik, Andrzej; Harms-Ringdahl, Mats; Atkinson, Michael J; Becker, Karl-Friedrich; Haghdoost, Siamak; Tapio, Soile

    2013-01-01

    The etiology of radiation-induced cardiovascular disease (CVD) after chronic exposure to low doses of ionizing radiation is only marginally understood. We have previously shown that a chronic low-dose rate exposure (4.1 mGy/h) causes human umbilical vein endothelial cells (HUVECs) to prematurely senesce. We now show that a dose rate of 2.4 mGy/h is also able to trigger premature senescence in HUVECs, primarily indicated by a loss of growth potential and the appearance of the senescence-associated markers ß-galactosidase (SA-ß-gal) and p21. In contrast, a lower dose rate of 1.4 mGy/h was not sufficient to inhibit cellular growth or increase SA-ß-gal-staining despite an increased expression of p21. We used reverse phase protein arrays and triplex Isotope Coded Protein Labeling with LC-ESI-MS/MS to study the proteomic changes associated with chronic radiation-induced senescence. Both technologies identified inactivation of the PI3K/Akt/mTOR pathway accompanying premature senescence. In addition, expression of proteins involved in cytoskeletal structure and EIF2 signaling was reduced. Age-related diseases such as CVD have been previously associated with increased endothelial cell senescence. We postulate that a similar endothelial aging may contribute to the increased rate of CVD seen in populations chronically exposed to low-dose-rate radiation.

  7. The PI3K/Akt/mTOR Pathway Is Implicated in the Premature Senescence of Primary Human Endothelial Cells Exposed to Chronic Radiation

    PubMed Central

    Yentrapalli, Ramesh; Azimzadeh, Omid; Sriharshan, Arundhathi; Malinowsky, Katharina; Merl, Juliane; Wojcik, Andrzej; Harms-Ringdahl, Mats; Atkinson, Michael J.; Becker, Karl-Friedrich; Haghdoost, Siamak; Tapio, Soile

    2013-01-01

    The etiology of radiation-induced cardiovascular disease (CVD) after chronic exposure to low doses of ionizing radiation is only marginally understood. We have previously shown that a chronic low-dose rate exposure (4.1 mGy/h) causes human umbilical vein endothelial cells (HUVECs) to prematurely senesce. We now show that a dose rate of 2.4 mGy/h is also able to trigger premature senescence in HUVECs, primarily indicated by a loss of growth potential and the appearance of the senescence-associated markers ß-galactosidase (SA-ß-gal) and p21. In contrast, a lower dose rate of 1.4 mGy/h was not sufficient to inhibit cellular growth or increase SA-ß-gal-staining despite an increased expression of p21. We used reverse phase protein arrays and triplex Isotope Coded Protein Labeling with LC-ESI-MS/MS to study the proteomic changes associated with chronic radiation-induced senescence. Both technologies identified inactivation of the PI3K/Akt/mTOR pathway accompanying premature senescence. In addition, expression of proteins involved in cytoskeletal structure and EIF2 signaling was reduced. Age-related diseases such as CVD have been previously associated with increased endothelial cell senescence. We postulate that a similar endothelial aging may contribute to the increased rate of CVD seen in populations chronically exposed to low-dose-rate radiation. PMID:23936371

  8. Transgenerational accumulation of radiation damage in small mammals chronically exposed to Chernobyl fallout.

    PubMed

    Ryabokon, Nadezhda I; Goncharova, R I

    2006-09-01

    The purpose of this investigation has been the analysis of the long-term development of biological damage in natural populations of a model mammalian species, the bank vole (Clethrionomys glareolus, Schreber), which were chronically exposed to low doses of ionizing radiation over 22 animal generations within 10 years following the Chernobyl accident. The time course of the biological end-points (chromosome aberrations in bone marrow cells and embryonic lethality) was compared with the time course of the whole-body absorbed dose rate from external and internal exposure in the studied populations inhabiting monitoring sites in Belarus with different ground deposition of radionuclides. The yield of chromosome aberrations and, in lesser degree, embryonic lethality was associated with the radionuclide contamination of the monitoring areas in a dose-dependent manner. As a main feature of the long-term development of biological damage under low dose rate irradiation, permanently elevated levels of chromosome aberrations and an increasing frequency of embryonic lethality have developed over 22 animal generations. This contrasts with the assumption that the biological damage would gradually disappear since in the same period of time the whole-body absorbed dose rate decreased exponentially with a half-value time of about 2.5-3 years. Furthermore, gravid females were captured, and their offspring, born and grown up under contamination-free laboratory conditions, showed the same enhanced level of chromosome aberrations. Therefore the authors suggest that, along with the biological damage attributable to the individual exposure of each animal, the observed cellular and systemic effects reflect the transgenerational transmission and accumulation, via genetic and/or epigenetic pathways, of damage attributable to the chronic low-dose rate exposure of the preceding generations of animals. They also suggest that the level of the accumulated transmissible damage in the investigated

  9. [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].

    PubMed

    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

  10. Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer

    PubMed Central

    Warner, Andrew; Pickles, Tom; Crook, Juanita; Martin, Andre-Guy; Souhami, Luis; Catton, Charles; Lukka, Himu

    2015-01-01

    Purpose: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II “Phoenix” definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database. Methods and Materials: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy  (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates. Results: Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT. Conclusions: Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and

  11. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    SciTech Connect

    Li, Chuan-Yaun

    2009-01-27

    “Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  12. Towards the clinical implementation of iterative low-dose cone-beam CT reconstruction in image-guided radiation therapy: Cone/ring artifact correction and multiple GPU implementation

    SciTech Connect

    Yan, Hao E-mail: xun.jia@utsouthwestern.edu; Shi, Feng; Jiang, Steve B.; Jia, Xun E-mail: xun.jia@utsouthwestern.edu; Wang, Xiaoyu; Cervino, Laura; Bai, Ti; Folkerts, Michael

    2014-11-01

    , an overall 3.1 × speedup factor has been achieved with four GPU cards compared to a single GPU-based reconstruction. The total computation time is ∼30 s for typical clinical cases. Conclusions: The authors have developed a low-dose CBCT IR system for IGRT. By incorporating data consistency-based weighting factors in the IR model, cone/ring artifacts can be mitigated. A boost in computational efficiency is achieved by multi-GPU implementation.

  13. Towards the clinical implementation of iterative low-dose cone-beam CT reconstruction in image-guided radiation therapy: Cone/ring artifact correction and multiple GPU implementation

    PubMed Central

    Yan, Hao; Wang, Xiaoyu; Shi, Feng; Bai, Ti; Folkerts, Michael; Cervino, Laura; Jiang, Steve B.; Jia, Xun

    2014-01-01

    , an overall 3.1 × speedup factor has been achieved with four GPU cards compared to a single GPU-based reconstruction. The total computation time is ∼30 s for typical clinical cases. Conclusions: The authors have developed a low-dose CBCT IR system for IGRT. By incorporating data consistency-based weighting factors in the IR model, cone/ring artifacts can be mitigated. A boost in computational efficiency is achieved by multi-GPU implementation. PMID:25370645

  14. Enhanced Low Dose Rate Effects in Bipolar Circuits: A New Hardness Assurance Problem for NASA

    NASA Technical Reports Server (NTRS)

    Johnston, A.; Barnes, C.

    1995-01-01

    Many bipolar integrated circuits are much more susceptible to ionizing radiation at low dose rates than they are at high dose rates typically used for radiation parts testing. Since the low dose rate is equivalent to that seen in space, the standard lab test no longer can be considered conservative and has caused the Air Force to issue an alert. Although a reliable radiation hardness assurance test has not yet been designed, possible mechanisms for low dose rate enhancement and hardness assurance tests are discussed.

  15. Chronic haemorrhagic radiation proctitis: A review.

    PubMed

    Nelamangala Ramakrishnaiah, Vishnu Prasad; Krishnamachari, Srinivasan

    2016-07-27

    Chronic haemorrhagic radiation proctitis (CHRP) is a difficult problem faced by the patients following radiation for pelvic malignancy. There is no standard treatment for this condition, but many methods of treatment are available. The aim of this study was to review the literature to see whether there is an improvement in the available evidence in comparison with previously published systematic reviews in treating patients with CHRP. The PubMed/Medline database and Google Scholar search was selectively searched. Studies, which treated patients with rectal bleeding due to chronic radiation proctitis or CHRP, were included. Seventy studies were finally selected out of which 14 were randomized controlled clinical trials. Though these studies could not be compared, it could be seen that there was an improvement in the methodology of the studies. There was an objective assessment of symptoms, signs and an objective assessment of outcomes. But, still, there were only a few studies that looked into the quality of life following treatment of CHRP. To increase recruitment to trials, a national registry of cases with established late radiation toxicity would facilitate the further improvement of such studies. Some of the conclusions that could be reached based on the available evidence are 4% formalin should be the first line treatment for patients with CHRP. Formalin and argon plasma coagulation (APC) are equally effective, but formalin is better for severe disease. Refractory patients, not responding to formalin or APC, need to be referred for hyperbaric oxygen therapy or surgery. Radio-frequency ablation is a promising modality that needs to be studied further in randomized trials. PMID:27462390

  16. Chronic haemorrhagic radiation proctitis: A review

    PubMed Central

    Nelamangala Ramakrishnaiah, Vishnu Prasad; Krishnamachari, Srinivasan

    2016-01-01

    Chronic haemorrhagic radiation proctitis (CHRP) is a difficult problem faced by the patients following radiation for pelvic malignancy. There is no standard treatment for this condition, but many methods of treatment are available. The aim of this study was to review the literature to see whether there is an improvement in the available evidence in comparison with previously published systematic reviews in treating patients with CHRP. The PubMed/Medline database and Google Scholar search was selectively searched. Studies, which treated patients with rectal bleeding due to chronic radiation proctitis or CHRP, were included. Seventy studies were finally selected out of which 14 were randomized controlled clinical trials. Though these studies could not be compared, it could be seen that there was an improvement in the methodology of the studies. There was an objective assessment of symptoms, signs and an objective assessment of outcomes. But, still, there were only a few studies that looked into the quality of life following treatment of CHRP. To increase recruitment to trials, a national registry of cases with established late radiation toxicity would facilitate the further improvement of such studies. Some of the conclusions that could be reached based on the available evidence are 4% formalin should be the first line treatment for patients with CHRP. Formalin and argon plasma coagulation (APC) are equally effective, but formalin is better for severe disease. Refractory patients, not responding to formalin or APC, need to be referred for hyperbaric oxygen therapy or surgery. Radio-frequency ablation is a promising modality that needs to be studied further in randomized trials. PMID:27462390

  17. Induction of reciprocal translocations in rhesus monkey stem-cell spermatogonia: effects of low doses and low dose rates

    SciTech Connect

    van Buul, P.P.; Richardson, J.F. Jr.; Goudzwaard, J.H.

    1986-01-01

    The induction of reciprocal translocation in rhesus monkey spermatogonial stem cells was studied following exposure to low doses of acute X rays (0.25 Gy, 300 mGy/min) or to low-dose-rate X rays (1 Gy, 2 mGy/min) and gamma rays (1 Gy, 0.2 mGy/min). The results obtained at 0.25 Gy of X rays fitted exactly the linear extrapolation down from the 0.5 and 1.0 Gy points obtained earlier. Extension of X-ray exposure reduced the yield of translocations similar to that in the mouse by about 50%. The reduction to 40% of translocation rate after chronic gamma exposure was clearly less than the value of about 80% reported for the mouse over the same range of dose rates. Differential cell killing with ensuing differential elimination of aberration-carrying cells is the most likely explanation for the differences between mouse and monkey.

  18. Tardive dyskinesia with low dose amisulpride.

    PubMed

    Tharoor, Hema; Padmavati, R

    2013-01-01

    In recent years, there has been an increasing trend to use amisulpride in the treatment of dysthymia and also as an adjunct treatment in patients with major depression. At low doses (50 mg), amisulpride preferentially blocks presynaptic auto receptors, enhances dopamine release, and therefore acts as a dopaminergic compound able to resolve the dopaminergic hypo activity that characterizes depression. Based on experimental data, amisulpride is the drug of choice for dopaminergic transmission disorders, both in depression and in schizophrenia. This case highlights the development of dyskinesia in a depressed patient treated with low dose amisulpride and fluvoxamine.

  19. A Simple Low-dose X-ray CT Simulation from High-dose Scan

    PubMed Central

    Zeng, Dong; Huang, Jing; Bian, Zhaoying; Niu, Shanzhou; Zhang, Hua; Feng, Qianjin; Liang, Zhengrong

    2015-01-01

    Low-dose X-ray computed tomography (CT) simulation from high-dose scan is required in optimizing radiation dose to patients. In this study, we propose a simple low-dose CT simulation strategy in sinogram domain using the raw data from high-dose scan. Specially, a relationship between the incident fluxes of low- and high- dose scans is first determined according to the repeated projection measurements and analysis. Second, the incident flux level of the simulated low-dose scan is generated by properly scaling the incident flux level of high-dose scan via the determined relationship in the first step. Third, the low-dose CT transmission data by energy integrating detection is simulated by adding a statistically independent Poisson noise distribution plus a statistically independent Gaussian noise distribution. Finally, a filtered back-projection (FBP) algorithm is implemented to reconstruct the resultant low-dose CT images. The present low-dose simulation strategy is verified on the simulations and real scans by comparing it with the existing low-dose CT simulation tool. Experimental results demonstrated that the present low-dose CT simulation strategy can generate accurate low-dose CT sinogram data from high-dose scan in terms of qualitative and quantitative measurements. PMID:26543245

  20. Etched track detectors and the low dose problem.

    PubMed

    Pálfalvi, J; Dám, A M; Bogdándi, E N; Polonyi, I; Szabó, J; Balásházy, I; Farkas, A

    2003-01-01

    The risk to human health of exposure to low-level radiation is not precisely known yet. One way of studying this is to carry out in vitro biological experiments with cell cultures and to extend the conclusions to biological models. To relate the macroscopically deteminable 'low dose' to the damage of cells caused by a certain type of ionising particle is nearly impossible. therefore the number of hits and the imparted energy are the significant quantities. They can be estimated by particle transport calculations and by direct measurements. The effect of low dose was investigated in radio-adaptation experiments when mono-layers of different unsynchronised cell cultures were irradiated by neutrons produced in the filtered beam of the Budapest Research Reactor (BRR). The energy deposition was investigated by replacing the mono-layers with etched track detectors of the CR-39 type. PMID:12678384

  1. Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery

    Cancer.gov

    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.

  2. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Yin, Xindao; Shi, Luyao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis; Toumoulin, Christine

    2013-08-01

    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.

  3. Chromosome Damage Caused by Accidental Chronic Whole-Body Gamma Radiation Exposure in Thailand

    PubMed Central

    Dolling, J.; Lavoie, J.; Mitchel, R. E. J.; Boreham, D. R.

    2015-01-01

    In February 2000, a radiation incident involving a medical 60Co source occurred in a metal scrapyard in Thailand. Several individuals were suspected to have received chronic or fractionated exposures ranging from a few mGy to a several Gy. Using fluorescence in situ hybridization to paint chromosomes, we determined the frequencies of chromosome aberrations in peripheral blood lymphocytes of 13 people who entered the scrapyard, 3 people who involved in recovering the source, and 9 nearby residents. Aberration frequencies greater than controls were observed in 13 of the donors at 3 months postexposure. The predominant form of aberration observed was simple, complete, symmetrical translocations. An approximate 50% decrease in these aberrations and in total color junctions was observed in 7 donors resampled at 16 months postexposure. Although high, acute exposures are known to have detrimental effects, the biological consequences of chronic, low dose-rate radiation exposures are unclear. Thirteen of the donors had elevated aberration frequencies, and 6 also had symptoms of acute radiation syndrome. If there are any long-term health consequences of this incident, it will most likely occur among this group of individuals. The consequences for the remaining donors, who presumably received lower total doses delivered at lower dose rates, are less clear. PMID:26740811

  4. Screening for lung cancer using low dose computed tomography.

    PubMed

    Tammemagi, Martin C; Lam, Stephen

    2014-01-01

    Screening for lung cancer with low dose computed tomography can reduce mortality from the disease by 20% in high risk smokers. This review covers the state of the art knowledge on several aspects of implementing a screening program. The most important are to identify people who are at high enough risk to warrant screening and the appropriate management of lung nodules found at screening. An accurate risk prediction model is more efficient than age and pack years of smoking alone at identifying those who will develop lung cancer and die from the disease. Algorithms are available for assessing people who screen positive to determine who needs additional imaging or invasive investigations. Concerns about low dose computed tomography screening include false positive results, overdiagnosis, radiation exposure, and costs. Further work is needed to define the frequency and duration of screening and to refine risk prediction models so that they can be used to assess the risk of lung cancer in special populations. Another important area is the use of computer vision software tools to facilitate high throughput interpretation of low dose computed tomography images so that costs can be reduced and the consistency of scan interpretation can be improved. Sufficient data are available to support the implementation of screening programs at the population level in stages that can be expanded when found to perform well to improve the outcome of patients with lung cancer. PMID:24865600

  5. Evaluation of in vivo low-dose mouse irradiation system

    NASA Astrophysics Data System (ADS)

    Noh, S. J.; Kim, H. J.; Kim, H.; Kye, Y.-U.; Kim, J. K.; Son, T. G.; Lee, M. W.; Jeong, D. H.; Yang, K. M.; Nam, S.-H.; Kang, Y.-R.

    2016-03-01

    This study aims to develop a facility that can irradiate subjects with a desired low dose, which can be used to assess the biological effects of low-dose radiation. We develop a single-occupancy mouse-cage and shelf system with adjustable geometric parameters, such as the distances and angles of the cages relative to the collimator. We assess the irradiation-level accuracy using two measurement methods. First, we calculate the angle and distance of each mouse cage relative to the irradiator. We employ a Monte Carlo n-particle simulation for all of the cages at a given distance from the radiation source to calculate the air kerma and the relative absorbed dose in the in-house designed shelving system; these are found to be approximately 0.108 and 0.109 Gy, respectively. Second, we measure the relative absorbed dose using glass dosimeters inserted directly into the heads and bodies of the mice. For a conventional irradiation system, the irradiation measurements show a maximum discrepancy of 42% between the absorbed and desired doses, whereas a discrepancy of only 6% from the desired dose is found for the designed mouse apartment system. In addition, multi-mouse cages are shown to yield to significantly greater differences in the mouse head and body relative absorbed doses, compared to the discrepancies found for single-occupancy cages in the conventional irradiation system. Our findings suggest that the in-house shelving system has greater reliability for the biological analysis of the effects of low-dose radiation.

  6. Low Dose IR Creates an Oncogenic Microenvironment by Inducing Premature

    SciTech Connect

    Yuan, Zhi-Min

    2013-04-28

    Introduction Much of the work addressing ionizing radiation-induced cellular response has been carried out mainly with the traditional cell culture technique involving only one cell type, how cellular response to IR is influenced by the tissue microenvironment remains elusive. By use of a three-dimensional (3D) co-culture system to model critical interactions of different cell types with their neighbors and with their environment, we recently showed that low-dose IR-induced extracellular signaling via the tissue environment affects profoundly cellular responses. This proposal aims at determining the response of mammary epithelial cells in a tissue-like setting.

  7. Influence on cell proliferation of background radiation or exposure to very low, chronic gamma radiation. [Paramecium tetraurelia; Synechococcus lividus

    SciTech Connect

    Planel, H.; Soleilhavoup, J.P.; Tixador, R.; Richoilley, G.; Conter, A.; Croute, F.; Caratero, C.; Gaubin, Y.

    1987-05-01

    Investigations carried out on the protozoan Paramecium tetraurelia and the cyanobacteria Synechococcus lividus, which were shielded against background radiation or exposed to very low doses of gamma radiation, demonstrated that radiation can stimulate the proliferation of these two single-cell organisms. Radiation hormesis depends on internal factors (age of starting cells) and external factors (lighting conditions). The stimulatory effect occurred only in a limited range of doses and disappeared for dose rates higher than 50 mGy/y.

  8. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    SciTech Connect

    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

  9. [Low dose naltrexone for treatment of pain].

    PubMed

    Plesner, Karin Bruun; Vægter, Henrik Bjarke; Handberg, Gitte

    2015-10-01

    Recent years have seen an increasing interest in the use of low dose naltrexone (LDN) for off-label treatment of pain in diseases as fibromyalgia, multiple sclerosis and morbus Crohn. The evidence is poor, with only few randomized double-blind placebo-controlled studies. The studies currently available are reviewed in this paper. LDN could be a potentially useful drug in the future for the treatment of pain in fibromyalgia, but more studies are needed to verify that it is superior to placebo, and currently it cannot be recommended as first-line therapy. PMID:26509454

  10. Analysis of cellular response by exposure to acute or chronic radiation in human lymphoblastoid TK-6 cells

    NASA Astrophysics Data System (ADS)

    Ohnishi, T.; Yasumoto, J.; Takahashi, A.; Ohnishi, K.

    To clarify the biological effects of low-dose rate radiation on human health for long-term stay in space, we analyzed the induction of apoptosis and apoptosis-related gene expression after irradiation with different dose-rate in human lymphoblastoid TK-6 cells harboring wild-type p53 gene. We irradiated TK-6 cells by X-ray at 1.5 Gy (1 Gy/min) and then sampled at 25 hr after culturing. We also irradiated by gamma-ray at 1.5 Gy (1 mGy/min) and then sampled immediately or 25 hr after irradiation. For DNA ladder analysis, we extracted DNA from these samples and electrophoresed with 2% agarose gel. In addition, we extracted mRNA from these samples for DNA-array analysis. mRNA from non-irradiated cells was used as a control. After labeling the cDNA against mRNA with [α -33P]-dCTP and hybridizing onto DNA array (Human Apoptosis Expression Array, R&D Systems), we scanned the profiles of the spots by a phosphorimager (BAS5000, FUJI FILM) and calculated using a NIH Image program. The data of each DNA-array were normalized with eight kinds of house keeping genes. We analyzed the expression level of apoptosis-related genes such as p53-related, Bcl-2 family, Caspase family and Fas-related genes. DNA ladders were obviously detected in the cells exposed to a high dose-rate radiation. We detected the induction of the gene expression of apoptosis-promotive genes. In contrast, almost no apoptosis was observed in the cells exposed to the chronic radiation at a low dose-rate. In addition, we detected the induction of the gene expression of apoptosis-suppressive genes as compared with apoptosis promotive-genes immediately after chronic irradiation. These results lead the importance of biological meaning of exposure to radiation at low dose-rate from an aspect of carcinogenesis. Finally, the effects of chronic irradiation become a highly important issue in space radiation biology for human health.

  11. Culmination of Low-Dose Pesticide Effects

    PubMed Central

    2013-01-01

    Pesticides applied in agriculture can affect the structure and function of nontarget populations at lower doses and for longer timespans than predicted by the current risk assessment frameworks. We identified a mechanism for this observation. The populations of an aquatic invertebrate (Culex pipiens) exposed over several generations to repeated pulses of low concentrations of the neonicotinoid insecticide (thiacloprid) continuously declined and did not recover in the presence of a less sensitive competing species (Daphnia magna). By contrast, in the absence of a competitor, insecticide effects on the more sensitive species were only observed at concentrations 1 order of magnitude higher, and the species recovered more rapidly after a contamination event. The underlying processes are experimentally identified and reconstructed using a simulation model. We conclude that repeated toxicant pulse of populations that are challenged with interspecific competition may result in a multigenerational culmination of low-dose effects. PMID:23859631

  12. Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

    ClinicalTrials.gov

    2016-10-24

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

  13. Low-dose aripiprazole for refractory burning mouth syndrome.

    PubMed

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. PMID:27279742

  14. Low-dose aripiprazole for refractory burning mouth syndrome

    PubMed Central

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. PMID:27279742

  15. Leukemia incidence among people exposed to chronic radiation from the contaminated Techa River, 1953-2005.

    PubMed

    Krestinina, Lyudmila; Preston, Dale L; Davis, Faith G; Epifanova, Svetlana; Ostroumova, Evgenia; Ron, Elaine; Akleyev, Alexander

    2010-05-01

    Beginning in 1950, people living on the banks of the Techa River received chronic low-dose-rate internal and external radiation exposures as a result of releases from the Mayak nuclear weapons plutonium production facility in the Southern Urals region of the Russian Federation. The Techa River cohort includes about 30,000 people who resided in riverside villages sometime between 1950 and 1960. Cumulative red bone marrow doses range up to 2 Gy with a mean of 0.3 Gy and a median of 0.2 Gy. Between 1953 and 2005, 93 first primary cases of leukemia, including 23 cases of chronic lymphatic leukemia (CLL), were ascertained among the cohort members. A significant linear dose-response relationship was seen for leukemias other than CLL (P < 0.001), but not for CLL. The estimated excess relative risk per Gy is 4.9 (95% confidence interval (CI): 1.6; 14.3) for leukemias other than CLL and less than 0 (95% upper bound 1.4) for CLL. PMID:20012750

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

    PubMed

    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. PMID:27218294

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

    PubMed

    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. The Effects of ELDRS at Ultra-Low Dose Rates

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi; Holcombe, Bruce; Little, Bradley; Salzman, James; Chaumont, Geraldine; Duperray, Herve; Ouellet, Al

    2011-01-01

    We present results on the effects on ELDRS at dose rates of 10, 5, 1, and 0.5 mrad(Si)/s for a variety of radiation hardened and commercial devices. We observed low dose rate enhancement below 10 mrad(Si)/s in several different parts. The magnitudes of the dose rate effects vary. The TL750L, a commercial voltage regulator, showed dose rate dependence in the functional failures, with initial failures occurring after 10 krad(Si) for the parts irradiated at 0.5 mrad(Si)/s. The RH1021 showed an increase in low dose rate enhancement by 2x at 5 mrad(Si)/s relative to 8 mrad(Si)/s and high dose rate, and parametric failure after 100 krad(Si). Additionally the ELDRS-free devices, such as the LM158 and LM117, showed evidence of dose rate sensitivity in parametric degradations. Several other parts also displayed dose rate enhancement, with relatively lower degradations up to approx.15 to 20 krad(Si). The magnitudes of the dose rate enhancement will likely increase in significance at higher total dose levels.

  19. Telomere Length in Aged Mayak PA Nuclear Workers Chronically Exposed to Internal Alpha and External Gamma Radiation.

    PubMed

    Scherthan, Harry; Sotnik, Natalia; Peper, Michel; Schrock, Gerrit; Azizova, Tamara; Abend, Michael

    2016-06-01

    Telomeres consist of GC-rich DNA repeats and the "shelterin" protein complex that together protect chromosome ends from fusion and degradation. Telomeres shorten with age due to incomplete end replication and upon exposure to environmental and intrinsic stressors. Exposure to ionizing radiation is known to modulate telomere length. However, the response of telomere length in humans chronically exposed to radiation is poorly understood. Here, we studied relative telomere length (RTL) by IQ-FISH to leukocyte nuclei in a group of 100 workers from the plutonium production facility at the Mayak Production Association (PA) who were chronically exposed to alpha-emitting ((239)Pu) radiation and/or gamma (photon) radiation, and 51 local residents serving as controls, with a similar mean age of about 80 years. We applied generalized linear statistical models adjusted for age at biosampling and the second exposure type on a linear scale and observed an age-dependent telomere length reduction. In those individuals with the lowest exposure, a significant reduction of about 20% RTL was observed, both for external gamma radiation (≤1 Gy) and internal alpha radiation (≤0.05-0.1 Gy to the red bone marrow). In highly exposed individuals (>0.1 Gy alpha, 1-1.5 Gy gamma), the RTL was similar to control. Stratification by gender revealed a significant (∼30%) telomere reduction in low-dose-exposed males, which was absent in females. While the gender differences in RTL may reflect different working conditions, lifestyle and/or telomere biology, absence of a dose response in the highly exposed individuals may reflect selection against cells with short telomeres or induction of telomere-protective effects. Our observations suggest that chronic systemic exposure to radiation leads to variable dose-dependent effects on telomere length. PMID:27340887

  20. Telomere Length in Aged Mayak PA Nuclear Workers Chronically Exposed to Internal Alpha and External Gamma Radiation.

    PubMed

    Scherthan, Harry; Sotnik, Natalia; Peper, Michel; Schrock, Gerrit; Azizova, Tamara; Abend, Michael

    2016-06-01

    Telomeres consist of GC-rich DNA repeats and the "shelterin" protein complex that together protect chromosome ends from fusion and degradation. Telomeres shorten with age due to incomplete end replication and upon exposure to environmental and intrinsic stressors. Exposure to ionizing radiation is known to modulate telomere length. However, the response of telomere length in humans chronically exposed to radiation is poorly understood. Here, we studied relative telomere length (RTL) by IQ-FISH to leukocyte nuclei in a group of 100 workers from the plutonium production facility at the Mayak Production Association (PA) who were chronically exposed to alpha-emitting ((239)Pu) radiation and/or gamma (photon) radiation, and 51 local residents serving as controls, with a similar mean age of about 80 years. We applied generalized linear statistical models adjusted for age at biosampling and the second exposure type on a linear scale and observed an age-dependent telomere length reduction. In those individuals with the lowest exposure, a significant reduction of about 20% RTL was observed, both for external gamma radiation (≤1 Gy) and internal alpha radiation (≤0.05-0.1 Gy to the red bone marrow). In highly exposed individuals (>0.1 Gy alpha, 1-1.5 Gy gamma), the RTL was similar to control. Stratification by gender revealed a significant (∼30%) telomere reduction in low-dose-exposed males, which was absent in females. While the gender differences in RTL may reflect different working conditions, lifestyle and/or telomere biology, absence of a dose response in the highly exposed individuals may reflect selection against cells with short telomeres or induction of telomere-protective effects. Our observations suggest that chronic systemic exposure to radiation leads to variable dose-dependent effects on telomere length.

  1. Optical fiber sensor for low dose gamma irradiation monitoring

    NASA Astrophysics Data System (ADS)

    de Andrés, Ana I.; Esteban, Ã.`scar; Embid, Miguel

    2016-05-01

    An optical fiber gamma ray detector is presented in this work. It is based on a Terbium doped Gadolinium Oxysulfide (Gd2O2S:Tb) scintillating powder which cover a chemically etched polymer fiber tip. This etching improves the fluorescence gathering by the optical fiber. The final diameter has been selected to fulfill the trade-off between light gathering and mechanical strength. Powder has been encapsulated inside a microtube where the fiber tip is immersed. The sensor has been irradiated with different air Kerma doses up to 2 Gy/h with a 137Cs source, and the spectral distribution of the fluorescence intensity has been recorded in a commercial grade CCD spectrometer. The obtained signal-to-noise ratio is good enough even for low doses, which has allowed to reduce the integration time in the spectrometer. The presented results show the feasibility for using low cost equipment to detect/measure ionizing radiation as gamma rays are.

  2. Radiobiological evaluation of low dose-rate prostate brachytherapy implants

    NASA Astrophysics Data System (ADS)

    Knaup, Courtney James

    Low dose-rate brachytherapy is a radiation therapy treatment for men with prostate cancer. While this treatment is common, the use of isotopes with varying dosimetric characteristics means that the prescription level and normal organ tolerances vary. Additionally, factors such as prostate edema, seed loss and seed migration may alter the dose distribution within the prostate. The goal of this work is to develop a radiobiological response tool based on spatial dose information which may be used to aid in treatment planning, post-implant evaluation and determination of the effects of prostate edema and seed migration. Aim 1: Evaluation of post-implant prostate edema and its dosimetric and biological effects. Aim 2: Incorporation of biological response to simplify post-implant evaluation. Aim 3: Incorporation of biological response to simplify treatment plan comparison. Aim 4: Radiobiologically based comparison of single and dual-isotope implants. Aim 5: Determine the dosimetric and radiobiological effects of seed disappearance and migration.

  3. Role of heme Oxygenase-1 in low dose Radioadaptive response

    PubMed Central

    Bao, Lingzhi; Ma, Jie; Chen, Guodong; Hou, Jue; Hei, Tom K.; Yu, K.N.; Han, Wei

    2016-01-01

    Radioadaptive response (RAR) is an important phenomenon induced by low dose radiation. However, the molecular mechanism of RAR is obscure. In this study, we focused on the possible role of heme oxygenase 1 (HO-1) in RAR. Consistent with previous studies, priming dose of X-ray radiation (1–10 cGy) induced significant RAR in normal human skin fibroblasts (AG 1522 cells). Transcription and translation of HO-1 was up-regulated more than two fold by a priming dose of radiation (5 cGy). Zinc protoporphyrin Ⅸ, a specific competitive inhibitor of HO-1, efficiently inhibited RAR whereas hemin, an inducer of HO-1, could mimic priming dose of X-rays to induce RAR. Knocking down of HO-1 by transfection of HO-1 siRNA significantly attenuated RAR. Furthermore, the expression of HO-1 gene was modulated by the nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which translocated from cytoplasm to nucleus after priming dose radiation and enhance the antioxidant level of cells. PMID:26966892

  4. Chronic neuroendocrinological sequelae of radiation therapy

    SciTech Connect

    Sklar, C.A.; Constine, L.S.

    1995-03-30

    A variety of neuroendocrine disturbances are observed following treatment with external radiation therapy when the hypothalamic-pituitary axis (HPA) is included in the treatment field. Radiation-induced abnormalities are generally dose dependent and may develop many years after irradiation. Growth hormone deficiency and premature sexual development can occur following doses as low as 18 Gy fractionated radiation and are the most common neuroendocrine problems noted in children. Deficiency of gonadotropins, thyroid stimulating hormone, and adrenocorticotropin are seen primarily in individuals treated with > 40 Gy HPA irradiation. Hyperprolactinemia can be seen following high-dose radiotherapy (>40 Gy), especially among young women. Most neuroendocrine disturbances that develop as a result of HPA irradiation are treatable; patients at risk require long-term endocrine follow-up. 23 refs., 6 figs., 2 tabs.

  5. Low-dose effects of hormones and endocrine disruptors.

    PubMed

    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.

  6. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    EPA Science Inventory

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
    Cancer Responses
    .
    There has been a concerted effort in the field of radiation biology to better understand cellular
    responses that could have an impact on the estin1ation of cancer...

  7. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    SciTech Connect

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

    2015-08-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogoni