Depth-Dose and LET Distributions of Antiproton Beams in Various Target Materials

DEFF Research Database (Denmark)

Herrmann, Rochus; Olsen, Sune; Petersen, Jørgen B.B.

the annihilation process. Materials We have investigated the impact of substituting the target material on  the depth-dose distribution of pristine and  spread out antiproton beams using the FLUKA Monte Carlo transport program. Classical ICRP targets are compared to water phantoms. In addition, track average...... unrestricted LET is calculated for all configurations. Finally, we investigate which concentrations of gadolinium and boron are needed in a water target in order to observe a significant change in the antiproton depth-dose distribution.  Results Results indicate, that there is no significant change...... in the depth-dose distribution and average LET when substituting the materials. Adding boron and gadolinium up to concentrations of 1 per 1000 atoms to a water phantom, did not change the depth-dose profile nor the average LET. Conclusions  According to our FLUKA calculations, antiproton neutron capture...

Application of combined TLD and CR-39 PNTD method for measurement of total dose and dose equivalent on ISS

International Nuclear Information System (INIS)

Benton, E.R.; Deme, S.; Apathy, I.

2006-01-01

To date, no single passive detector has been found that measures dose equivalent from ionizing radiation exposure in low-Earth orbit. We have developed the I.S.S. Passive Dosimetry System (P.D.S.), utilizing a combination of TLD in the form of the self-contained Pille TLD system and stacks of CR-39 plastic nuclear track detector (P.N.T.D.) oriented in three mutually orthogonal directions, to measure total dose and dose equivalent aboard the International Space Station (I.S.S.). The Pille TLD system, consisting on an on board reader and a large number of Ca 2 SO 4 :Dy TLD cells, is used to measure absorbed dose. The Pille TLD cells are read out and annealed by the I.S.S. crew on orbit, such that dose information for any time period or condition, e.g. for E.V.A. or following a solar particle event, is immediately available. Near-tissue equivalent CR-39 P.N.T.D. provides Let spectrum, dose, and dose equivalent from charged particles of LET ∞ H 2 O ≥ 10 keV/μm, including the secondaries produced in interactions with high-energy neutrons. Dose information from CR-39 P.N.T.D. is used to correct the absorbed dose component ≥ 10 keV/μm measured in TLD to obtain total dose. Dose equivalent from CR-39 P.N.T.D. is combined with the dose component <10 keV/μm measured in TLD to obtain total dose equivalent. Dose rates ranging from 165 to 250 μGy/day and dose equivalent rates ranging from 340 to 450 μSv/day were measured aboard I.S.S. during the Expedition 2 mission in 2001. Results from the P.D.S. are consistent with those from other passive detectors tested as part of the ground-based I.C.C.H.I.B.A.N. intercomparison of space radiation dosimeters. (authors)

Hit-size effectiveness theory applied to high doses of low LET radiation for pink mutations in Tradescantia

International Nuclear Information System (INIS)

Varma, M.N.; Bond, V.P.; Matthews, G.

1985-01-01

A hit-size effectiveness function which represents the probability of inducing a pink mutation in Tradescantia as a function of lineal energy density has been obtained (1) using observed pink mutation data for seven different radiation qualities and their respective single event microdosimetric spectra. In obtaining this function only the linear portions of dose-response curves were used. A significant improvement of the concepts embodied in the proposed hit-size effectiveness theory would be the demonstration of its applicability at high doses (where multiple hits are produced) and high dose rates (at which no significant biological repair takes place). In this article details are given on preliminary calculations of the pink mutation frequency in Tradescantia at 1, 5, 10, 20, and 60 rads for 250 kVp x rays, using the multi-hit spectra and the hit-size effectiveness function obtained on the basis of single hit microdosimetric spectra as outline in (1). A comparison of the calculated and observed pink mutation frequencies indicate excellent agreement and suggests the possibility of obtaining the hit-size effectiveness function from high dose biological-effect data obtained using low-LET radiations. 6 refs., 3 figs., 3 tabs

The inactivation of papain by high LET radiations

International Nuclear Information System (INIS)

Bisby, R.H.; Cundall, R.B.; Sims, H.E.; Burns, W.G.

1984-01-01

The effect of varying LET over a wide range (0.2-1570 eV/nm) on the radiation-induced inactivation of the enzyme papain in dilute aqueous solution has been investigated. Measurements of total, reparable and non-reparable inactivation G values in oxygen, nitrous oxide and argon saturated solutions have allowed the contributions to inactivation from radicals and hydrogen peroxide to be evaluated. At high LET the results demonstrate an increasing component due to reaction of the superoxide radical, formed from oxygen produced in the track as a primary radiolysis product. This effect was not observed in our previous study with ribonuclease due to the insensitivity of ribonuclease to inactivation by superoxide and hydrogen peroxide. The results obtained with papain clearly demonstrate a maximum in G(H 2 O 2 ) at an LET of equivalent to 140 eV/nm. Generation of O 2 within the track as a primary radiolysis product at high LET now appears to be confirmed as an important mechanism leading to reduction in the oxygen enhancement ratio for cellular systems exposed to high LET radiations (Baverstock and Burns 1981). (author)

Dose rate effects of low-LET ionizing radiation on fish cells

Energy Technology Data Exchange (ETDEWEB)

Vo, Nguyen T.K. [McMaster University, Radiation Sciences Program, School of Graduate and Postdoctoral Studies, Hamilton, ON (Canada); Seymour, Colin B.; Mothersill, Carmel E. [McMaster University, Radiation Sciences Program, School of Graduate and Postdoctoral Studies, Hamilton, ON (Canada); McMaster University, Department of Biology, Hamilton, ON (Canada)

2017-11-15

Radiobiological responses of a highly clonogenic fish cell line, eelB, to low-LET ionizing radiation and effects of dose rates were studied. In acute exposure to 0.1-12 Gy of gamma rays, eelB's cell survival curve displayed a linear-quadratic (LQ) relationship. In the LQ model, α, β, and α/β ratio were 0.0024, 0.037, and 0.065, respectively; for the first time that these values were reported for fish cells. In the multi-target model, n, D{sub o}, and D{sub q} values were determined to be 4.42, 2.16, and 3.21 Gy, respectively, and were the smallest among fish cell lines being examined to date. The mitochondrial potential response to gamma radiation in eelB cells was at least biphasic: mitochondria hyperpolarized 2 h and then depolarized 5 h post-irradiation. Upon receiving gamma rays with a total dose of 5 Gy, dose rates (ranging between 83 and 1366 mGy/min) had different effects on the clonogenic survival but not the mitochondrial potential. The clonogenic survival was significantly higher at the lowest dose rate of 83 mGy/min than at the other higher dose rates. Upon continuous irradiation with beta particles from tritium at 0.5, 5, 50, and 500 mGy/day for 7 days, mitochondria significantly depolarized at the three higher dose rates. Clearly, dose rates had differential effects on the clonogenic survival of and mitochondrial membrane potential in fish cells. (orig.)

A composite microdose Adaptive Response (AR) and Bystander Effect (BE) model-application to low LET and high LET AR and BE data.

Science.gov (United States)

Leonard, Bobby E

2008-08-01

It has been suggested that Adaptive Response (AR) may reduce risk of adverse health effects due to ionizing radiation. But very low dose Bystander Effects (BE) may impose dominant deleterious human risks. These conflicting behaviors have stimulated controversy regarding the Linear No-Threshold human risk model. A dose and dose rate-dependent microdose model, to examine AR behavior, was developed in prior work. In the prior work a number of in vitro and in vivo dose response data were examined with the model. Recent new data show AR behavior with some evidence of very low dose BE. The purpose of this work is to supplement the microdose model to encompass the Brenner and colleagues BaD (Bystander and Direct Damage) model and apply this composite model to obtain new knowledge regarding AR and BE and illustrate the use of the model to plan radio-biology experiments. The biophysical composite AR and BE Microdose Model quantifies the accumulation of hits (Poisson distributed, microdose specific energy depositions) to cell nucleus volumes. This new composite AR and BE model provides predictions of dose response at very low dose BE levels, higher dose AR levels and even higher dose Direct (linear-quadratic) Damage radiation levels. We find good fits of the model to both BE data from the Columbia University microbeam facility and combined AR and BE data for low Linear Energy Transfer (LET) and high LET data. A Bystander Factor of about 27,000 and an AR protection factor of 0.61 are obtained for the low LET in vivo mouse spleen exposures. A Bystander Factor of 317 and an AR protection factor of 0.53 are obtained for high LET radon alpha particles in human lymphocytes. In both cases the AR is activated at most by one or two radiation induced charged particle traversals through the cell nucleus. The results of the model analysis is consistent with a premise that both Bystander damage and Adaptive Response radioprotection can occur in the same cell type, derived from the same

Track structure analysis illustrating the prominent role of low-energy electrons in radiobiological effects of low-LET radiations

International Nuclear Information System (INIS)

Nikjoo, H.; Goodhead, D.T.

1991-01-01

Monte Carlo track structure methods have been used to illustrate the importance of low-energy electrons produced by low-LET radiations. It is shown that these low-energy secondary electrons contribute substantially to the dose in all low-LET irradiations and are particularly efficient at producing highly localized clusters of atomic damage which may be responsible for a major part of the biological effectiveness of low-LET radiations. The data generated by Monte Carlo track structure techniques and by earlier semi-analytical methods based on the LET concept have been compared in terms of cumulative and differential fractions of total dose absorbed as a function of electron energy. The data show that low-energy secondary electrons account for up to nearly 50% of the total dose imparted to a medium when irradiated with electrons or photons. (author)

Use of BEIR V and UNSCEAR 1988 in radiation risk assessment: Lifetime total cancer mortality risk estimates at low doses and low dose rates for low-LET radiation

International Nuclear Information System (INIS)

1992-12-01

In November 1986, the Department of Defense (DoD) asked the Committee on Interagency Radiation Research and Policy Coordination (CIRRPC) to develop a coordinated Federal position on risk assessment for low levels of ionizing radiation. Since Federal risk assessment activities are based primarily on the scientific data and analyses in authoritative review documents prepared by groups like the National Academy of Sciences' Committee on the Biological Effects of Ionizing Radiation (BEIR), the National Council on Radiation Protection and Measurements (NCRP) and the United Nations' Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), DoD proposed that the CIRRPC Science Panel undertake the task of providing coordinated interagency positions on the use of information in the reports of such groups. The practice has been for individual Federal agencies to interpret and decide independently how to use the information provided in such reports. As a result of its deliberations, the Subpanel recommends two nominal risk estimates for lifetime total cancer mortality following whole-body exposure to low levels of low-LET ionizing radiation, one for the general population and one for the working-age population (see Section II). The recommended risk estimates reflect the general agreement of information in BEIR V and UNSCEAR 1988 for total cancer mortality. The Subpanel's risk estimates and associated statements are intended to meet the needs of the Federal agencies for: (a) values that are current; (b) values that are relevant to the low-dose and low dose-rate ionizing radiation exposures principally encountered in carrying out Federal responsibilities; (c) a statement of the change in the estimates of lifetime total cancer mortality relative to estimates in previous authoritative review documents; and (d) a practical statement on the scientific uncertainty associated with applying the lifetime total cancer mortality values at very low doses

Alteration of cellular and subcellular electrophysiological parameters in mammalian cells by high- and low-LET irradiation at low dose-levels. Part of a coordinated programme on cell membrane probes as biological indicators in radiation accidents

International Nuclear Information System (INIS)

Pohl-Rueling, J.

1980-12-01

The transmembrane resting potential (MRP) was chosen as a highly sensitive indicator for cellular reactions. The MRP was studied for its suitability as biological indicator of the level of accidental radiation exposure. The development of methodology and installation of a low-cost test chamber, and dose-response studies of MRP-changes of human cells after irradiation with low- and high-LET radiation were considered. Cultured human embryonic lung fibroblasts and human lung biopsy samples were used, with a Co-60 source for low-LET irradiation at dose rates of 2 rad and 20 rad/min, respectively. For high-LET irradiation an Am-241 source was used. The onset of radiation induced effects on cell membranes was prompt but of short duration. In general, full recovery followed within hours of irradiation, at least under the particular experimental conditions. MRP changes in irradiated cells proved a highly sensitive parameter for assessing radiation effects on cell membranes. It appears premature to draw conclusions on the suitability of the method as a biological indicator of radiation damage from accidental exposure, in view of the short duration and prompt reversibility of the effects, and an incomplete understanding of the radiation-induced reactions involved at different LET's and at different doses and dose-rates

Microdosimetry of high LET therapeutic beams

International Nuclear Information System (INIS)

Ito, Akira

1980-01-01

Experimental microdosimetry of high LET therapeutic beams were presented. The cyclotron produced fast neutron beams at IMS, TAMVEC and NRL, a reactor fast neutron at YAYOI, a proctor beam at Harvard and a pion beam at TRIUMF are included. Measurements were performed with a conventional tissue equivalent spherical proportional counter with a logarithmic amplifier which made the recording and analysis quite simple. All the energy deposition spectra were analysed in the conventional manner and anti y F, anti y D as well as anti y D* were calculated. The spectra and their mean lineal energies showed wide variations, depending on the particle type, energy, position in phantom. Fractional contribution of elemental particles ( electron, muon, pion, proton, alpha and so on) to the total dose were analysed. For fast neutron beams, the y spectra stayed almost constant at any depth along the central axis in the phantom. The y spectra of proton beam changed slightly along the depth. On the other side, the y spectra of pion beam change drastically in the phantom between plateau and dose peak region. A novel technique of time-of-flight microdosimetry was employed, which made it possible to separate the fractional contribution of contaminant electrons and muons out of pions. Finally, a map of the radiation quality for all the beams is presented and its significances are discussed. (author)

Protein-directed modulation of high-LET hyperthermic radiosensitization

International Nuclear Information System (INIS)

Chang, P.Y.

1991-01-01

A pair of Chinese Hamster Ovary cell lines, the wild-type CHO-SC1, and its temperature-sensitive mutant (CHO-tsH1) was used to examine the importance of protein synthesis in the development of thermotolerance. The classical biphasic thermotolerant survival response to hyperthermia was observed in the SC1 cells after continuous heating at 41.5C to 42.5C, while tsH1 showed no thermotolerance. In separate experiments, each cell line was triggered and challenged at 45C. The heat doses were separated with graded incubaton periods at 35C or 40C for thermotolerance development. SC1 cells expressed thermoresistance, with the synthesis of heat shock proteins, under both incubation conditions. tsH1 cells expressed thermotolerance similar to that seen in the SC1 cells when incubated at 35C, but the survival response with the non-permissive 40C incubation was much reduced in the absence of protein synthesis. The combined effects of heavy-ion radiation and hyperthermia were examined using the same cell system. A mild heat dose of 41.5C was used in conjunction with Neon particle radiation of various high LET values. The cell killing effects were highly dependent on the sequence of application of heat and Neon radiation. Heat applied immediately after Neon irradiation was more cytotoxic to SC1 cells than when heat was applied prior to the irradiation. The ability of cells to synthesize new proteins plays a key role in this sequence-dependent thermal radiosensitization. In the absence of protein synthesis in the tsH1 cells, the high-LET thermal enhancement for cell-killing was unchanged regardless of the sequence. In the presence of protein synthetic activity in the SC1 cells, the thermal enhancement of radiation-induced cell killing was LET-dependent

Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

Energy Technology Data Exchange (ETDEWEB)

Vadhavkar, Nikhil [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Pham, Christopher [University of Texas, Houston, TX (United States). MD Anderson Cancer Center; Georgescu, Walter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Deschamps, Thomas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Heuskin, Anne-Catherine [Univ. of Namur (Belgium). Namur Research inst. for Life Sciences (NARILIS), Research Center for the Physics of Matter and Radiation (PMR); Tang, Jonathan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Costes, Sylvain V. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

2014-09-01

In contrast to the classic view of static DNA double-strand breaks (DSBs) being repaired at the site of damage, we hypothesize that DSBs move and merge with each other over large distances (m). As X-ray dose increases, the probability of having DSB clusters increases as does the probability of misrepair and cell death. Experimental work characterizing the X-ray dose dependence of radiation-induced foci (RIF) in nonmalignant human mammary epithelial cells (MCF10A) is used here to validate a DSB clustering model. We then use the principles of the local effect model (LEM) to predict the yield of DSBs at the submicron level. Two mechanisms for DSB clustering, namely random coalescence of DSBs versus active movement of DSBs into repair domains are compared and tested. Simulations that best predicted both RIF dose dependence and cell survival after X-ray irradiation favored the repair domain hypothesis, suggesting the nucleus is divided into an array of regularly spaced repair domains of ~;;1.55 m sides. Applying the same approach to high-linear energy transfer (LET) ion tracks, we are able to predict experimental RIF/m along tracks with an overall relative error of 12percent, for LET ranging between 30 350 keV/m and for three different ions. Finally, cell death was predicted by assuming an exponential dependence on the total number of DSBs and of all possible combinations of paired DSBs within each simulated RIF. Relative biological effectiveness (RBE) predictions for cell survival of MCF10A exposed to high-LET showed an LET dependence that matches previous experimental results for similar cell types. Overall, this work suggests that microdosimetric properties of ion tracks at the submicron level are sufficient to explain both RIF data and survival curves for any LET, similarly to the LEM assumption. Conversely, high-LET death mechanism does not have to infer linear-quadratic dose formalism as done in the LEM. In addition, the size of repair domains derived in our model

Gemcitabine radiosensitizes multiple myeloma cells to low let, but not high let, irradiation

International Nuclear Information System (INIS)

Supiot, Stephane; Thillays, Francois; Rio, Emmanuel; Gouard, Sebastien; Morgenstern, Alfred; Bruchertseifer, Frank; Mahe, Marc-Andre; Chatal, Jean-Francois; Davodeau, Francois; Cherel, Michel

2007-01-01

The radiosensitizing properties of gemcitabine in relation to low Linear Energy Transfer (LET) particles (Cobalt 60) and high-LET particles (alpha-RIT 213 Bi-radiolabeled CHX-DTPA-B-B4) were analyzed. Three multiple myeloma cell lines (LP1, RPMI 8226, U266) were irradiated with or without 10 nM gemcitabine 24 h prior to radiation. Gemcitabine led to radiosensitization of LP1 and U266 cells with low-LET (Radiation Enhancement Ratio: 1.55 and 1.49, respectively) but did not radiosensitize any cell line when combined with high-LET

High-LET particle exposure of Skylab astronauts

International Nuclear Information System (INIS)

Benton, E.V.; Peterson, D.D.; Bailey, J.V.; Parnell, T.

1977-01-01

High-LET particle radiation was registered in nuclear track recording plastic dosimeters worn on the wrists of Skylab astronauts and located in a heavily shielded film vault. The mission-average planar flux of high-LET particles with LET >= 100 keV/micron . tissue has been determined to be 2.7 +- 0.6 particles/cm 2 . day . 2π sr and 0.34 +- 0.4 particles/cm 2 . day . 2π sr, respectively, for the nine astronauts and for the film vault. Comparison of results representative of a wide range of shielding depths reveals that the magnitude and slope of the integral LET spectrum of high-LET particles inside spacecraft are proportional to the amount of shielding. (author)

Applications of high-throughput clonogenic survival assays in high-LET particle microbeams

Directory of Open Access Journals (Sweden)

Antonios eGeorgantzoglou

2016-01-01

Full Text Available Charged particle therapy is increasingly becoming a valuable tool in cancer treatment, mainly due to the favorable interaction of particle radiation with matter. Its application is still limited due, in part, to lack of data regarding the radiosensitivity of certain cell lines to this radiation type, especially to high-LET particles. From the earliest days of radiation biology, the clonogenic survival assay has been used to provide radiation response data. This method produces reliable data but it is not optimized for high-throughput microbeam studies with high-LET radiation where high levels of cell killing lead to a very low probability of maintaining cells’ clonogenic potential. A new method, therefore, is proposed in this paper, which could potentially allow these experiments to be conducted in a high-throughput fashion. Cells are seeded in special polypropylene dishes and bright-field illumination provides cell visualization. Digital images are obtained and cell detection is applied based on corner detection, generating individual cell targets as x-y points. These points in the dish are then irradiated individually by a micron field size high-LET microbeam. Post-irradiation, time-lapse imaging follows cells’ response. All irradiated cells are tracked by linking trajectories in all time-frames, based on finding their nearest position. Cell divisions are detected based on cell appearance and individual cell temporary corner density. The number of divisions anticipated is low due to the high probability of cell killing from high-LET irradiation. Survival curves are produced based on cell’s capacity to divide at least 4-5 times. The process is repeated for a range of doses of radiation. Validation shows the efficiency of the proposed cell detection and tracking method in finding cell divisions.

Applications of High-Throughput Clonogenic Survival Assays in High-LET Particle Microbeams.

Science.gov (United States)

Georgantzoglou, Antonios; Merchant, Michael J; Jeynes, Jonathan C G; Mayhead, Natalie; Punia, Natasha; Butler, Rachel E; Jena, Rajesh

2015-01-01

Charged particle therapy is increasingly becoming a valuable tool in cancer treatment, mainly due to the favorable interaction of particle radiation with matter. Its application is still limited due, in part, to lack of data regarding the radiosensitivity of certain cell lines to this radiation type, especially to high-linear energy transfer (LET) particles. From the earliest days of radiation biology, the clonogenic survival assay has been used to provide radiation response data. This method produces reliable data but it is not optimized for high-throughput microbeam studies with high-LET radiation where high levels of cell killing lead to a very low probability of maintaining cells' clonogenic potential. A new method, therefore, is proposed in this paper, which could potentially allow these experiments to be conducted in a high-throughput fashion. Cells are seeded in special polypropylene dishes and bright-field illumination provides cell visualization. Digital images are obtained and cell detection is applied based on corner detection, generating individual cell targets as x-y points. These points in the dish are then irradiated individually by a micron field size high-LET microbeam. Post-irradiation, time-lapse imaging follows cells' response. All irradiated cells are tracked by linking trajectories in all time-frames, based on finding their nearest position. Cell divisions are detected based on cell appearance and individual cell temporary corner density. The number of divisions anticipated is low due to the high probability of cell killing from high-LET irradiation. Survival curves are produced based on cell's capacity to divide at least four to five times. The process is repeated for a range of doses of radiation. Validation shows the efficiency of the proposed cell detection and tracking method in finding cell divisions.

Adaptive response to high LET radiations

International Nuclear Information System (INIS)

Dam, Annamaria; Bogdandi, E. Noemi; Polonyi, Istvan; Sardy, M. Marta; Balashazy, Imre; Palfalvy, Jozsef

2001-01-01

The biological consequences of exposure to ionizing radiation include gene mutation, chromosome aberrations, cellular transformation and cell death. These effects are attributed to the DNA damaging effects of the irradiation resulting in irreversible changes during DNA replication or during the processing of the DNA damage by enzymatic repair processes. These repair processes could initiate some adaptive mechanisms in the cell, which could lead to radioadaptive response (RAR). Adaptive responses have typically been detected by exposing cells to a low radiation dose (1-50 mGy) and then challenging the cells with a higher dose of radiation (2-4 Gy) and comparing the outcome to that seen with the challenge dose only. For adaptive response to be seen the challenge dose must be delivered within 24 hour of the inducing dose. Radio-adaptation is extensively studied for low LET radiation. Nevertheless, few data are available for high LET radiation at very low doses and dose rate. Our study was aimed to investigate the radioadaptive response to low-dose neutron irradiation by detection of the genotoxic damage i.e.: hprt-mutant colonies induced. Altered protein synthesis was also studied to identify stress proteins may responsible for radio-adaptation. New alpha particle irradiator system was also built up to study the biological effects of low dose alpha irradiation. The experiments were carried out on monolayers of human melanoma and CHO (Chines Hamster Ovary) cells irradiated by neutrons produced in the biological irradiation channel of the Research Reactor of Budapest Neutron Center. Cells were exposed to 0.5-50 mGy neutron doses with dose rates of 1.59-10 mGy/min. The challenge doses of 2-4 Gy gamma rays were administrated within 1-48 hours after priming treatment. The induced mutants at hprt locus were selected by adding 6-thioguanine and allow to grow for 10 days for expression of the phenotype. The protein synthesis was studied by PAGE, the molecular mass of specific

Chemical protection from high LET radiation

International Nuclear Information System (INIS)

Ando, Koichi; Koike, Sachiko; Matsushita, Satoru; Kanai, Tatsuaki; Ohara, Hiroshi

1992-01-01

Radioprotection by WR151327 from high LET fast neutrons was investigated and compared with that from low LET radiation. Radiation damage in bone marrow, intestine, skin and leg length were all protected by a pretreatment with 400 mg/kg WR151327. Most prominent protection was observed for bone marrow, which gave a Dose Modifying Factor (DMF) of 2.2 against γ rays. Identical protection was observed between early and late radiation damage. WR151327 protected fast neutrons less efficiently than γ rays; 40% for bone marrow and 80% for skin leg. Pathological findings indicated that hyperplastic change in both dermis and epidermis associated with late skin shrinkage. Laser doppler flow-metry showed a good relationship between reduction of blood flow and late skin shrinkage. Irradiation of skin by heavy particle Carbon-12 indicated that skin shrinkage was modified by unirradiated surrounding normal tissues, which proposed a significant role of 'Volume Effect' in radiation damage. Tumor tissues were less protected by WR151327 than normal tissues. Dependence of radioprotection by WR151327 on tissue oxygen concentration is a probable reason to explain the difference between normal and tumor tissues. (author)

TH-CD-209-06: LET-Based Adjustment of IMPT Plans Using Prioritized Optimization

Energy Technology Data Exchange (ETDEWEB)

Unkelbach, J; Giantsoudi, D; Paganetti, H [Massachusetts General Hospital, Boston, MA (United States); Botas, P [Massachusetts General Hospital, Boston, MA (United States); Heidelberg University, Heidelberg, DE (Germany); Qin, N; Jia, X [The University of Texas Southwestern Medical Ctr, Dallas, TX (United States)

2016-06-15

Purpose: In-vitro experiments suggest an increase in proton relative biological effectiveness (RBE) towards the end of range. However, proton treatment planning and dose reporting for clinical outcome assessment has been based on physical dose and constant RBE. Therefore, treatment planning for intensity-modulated proton therapy (IMPT) is unlikely to transition radically to pure RBE-based planning. We suggest a hybrid approach where treatment plans are initially created based on physical dose constraints and prescriptions, and are subsequently altered to avoid high linear energy transfer (LET) in critical structures while limiting the degradation of the physical dose distribution. Methods: To allow fast optimization based on dose and LET we extended a GPU-based Monte-Carlo code towards providing dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dose objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of physical dose and LET (LETxD). To first approximation, LETxD represents a measure of the additional biological dose that is caused by high LET. Regarding optimization techniques, LETxD has the advantage of being a linear function of the pencil beam intensities. Results: The method is applicable to treatments where serial critical structures with maximum dose constraint are located in or near the target. We studied intra-cranial tumors (high-grade meningiomas, base-of-skull chordomas) where the target (CTV) overlaps with the brainstem and optic structures. Often, high LETxD in critical structures can be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based re-optimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose

A critique of Katz's 'High LET constraint on low LET survival'

International Nuclear Information System (INIS)

Burch, P.R.J.; Chesters, M.S.

1979-01-01

Katz's interpretation of the connexion between RBE and LET is contrasted with a version published previously by Burch. The implications of Katz's model for dose-response relations apply only at ultra-high absorbed doses in Burch's model. In the latter, the shoulder on type-C survival curves for mammalian cells is explained in terms of Haynes' repair model. Under certain conditions the repair model becomes mathematically equivalent to the α-β model; under some other conditions it becomes equivalent to the 'two-component' model. The formulation of a new repair hypothesis, based on the idea of an inducible repair mechanism, is also set out. It is argued that Katz's supralinearity index' is appropriate to the induction of (rare) mutations but inappropriate to cell survival, for which an alternative index is proposed. Certain plausible hypotheses of radiobiological action conflict with Katz's 'logical constraint' which, it is contended, is neither logical nor valid. In conclusion, although experimental findings for some radiobiological systems conform to Katz's 'constraint', the frequently observed violations should not necessarily be regarded as artefacts. (author)

Neoplastic cell transformation by high-LET radiation - Molecular mechanisms

Science.gov (United States)

Yang, Tracy Chui-Hsu; Craise, Laurie M.; Tobias, Cornelius A.; Mei, Man-Tong

1989-01-01

Quantitative data were collected on dose-response curves of cultured mouse-embryo cells (C3H10T1/2) irradiated with heavy ions of various charges and energies. Results suggests that two breaks formed on DNA within 80 A may cause cell transformation and that two DNA breaks formed within 20 A may be lethal. From results of experiments with restriction enzymes which produce DNA damages at specific sites, it was found that DNA double strand breaks are important primary lesions for radiogenic cell transformation and that blunt-ended double-strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship for high-LET radiation is similar to that for HGPRT locus mutation, chromosomal deletion, and cell transformation, indicating that common lesions may be involved in these radiation effects.

Responses of epithelial cells to low and very low doses of low let radiation

International Nuclear Information System (INIS)

Mothersill, Carmel; Seymour, Colin

2003-01-01

Recent advances in our knowledge of the biological effects of low doses of ionizing radiation have shown unexpected phenomena. These vary in the endpoint used to detect them and in the dose range examined but all occur as high-frequency events in cell populations. They include: 1. a 'bystander effect' which can be demonstrated at low doses as a transferable.factor(s) causing radiobiological effects in unexposed cells, 2. an assortment of delayed effects' occurring in progeny of cells exposed to low doses, 3. Low-dose Hypersensitivity (HRS) and Increased radioresistance (IRR) which can collectively be demonstrated as a change in the dose-effect relationship, occurring around 0.5-1 Gy of low LET radiation and 4. adaptive responses where cells exposed to very low doses followed by higher doses, exhibit an induced relatively resistant response to the second dose. In all cases, the effect of very low doses is greater than would be predicted by extrapolation of high dose data and is inconsistent with conventional DNA break/repair-based radiobiology. In practical risk assessment terms, the relative importance of the effects are high at low doses where they dominate the response, and small at high doses. This paper reviews these assorted phenomena and in particular seeks to explore whether related or distinct mechanisms underlie these various effects Understanding the mechanistic basis of these phenomena may suggest new approaches to controlling death or survival sectoring at low radiation doses. The key question is whether these low dose phenomena necessitate a new approach to risk assessment. (author)

Production and excision of thymine damage in the DNA of mammalian cells exposed to high-LET radiations

International Nuclear Information System (INIS)

Mattern, M.R.; Welch, G.P.

1979-01-01

HeLa S3 and Chinese hamster ovary cells were irradiated with high doses of carbon ions having linear energy transfers (LETs) of 170 and 780 keV/μm. The DNA was analyzed for 5,6-dihydroxydihydrothymine (t'-type) radiation products both before and after postirradiation incubation at 37 0 C. In HeLa cells, 2.1 x 10 -5 ring-damaged thymines were produced per kilorad per 10 6 daltons after irradiation with high-LET carbon ions - approximately one-fifth the efficiency of t' formation in HeLa cells exposed to low-LET x rays. t' products were also formed less efficiently in Chinese hamster ovary cells exposed to carbon ions than in those exposed to x rays. In both cell lines, up to 80% of the t' formed initially was excised selectively from the DNA during 60 min of postirradiation incubation at 37 0 C. Product excision was accompanied by small amounts of DNA degradation (less than 1%). Radiation with LET of 170 keV/μm - nearly the most effective LET for cell killing and the generation of unrejoined DNA strand breaks - produced ring-damaged thymines that were removed selectively from the DNA. This result is consistent with the conclusion that t'-type products do not contribute substantially to lethality after high-LET irradiation, although the alternative possibilities remain that t' is not excised as efficiently after biological doses, or that a particular subclass of t' or defective postexcision events contribute to cell killing

Characterization of Radiation Hardened Bipolar Linear Devices for High Total Dose Missions

Science.gov (United States)

McClure, Steven S.; Harris, Richard D.; Rax, Bernard G.; Thorbourn, Dennis O.

2012-01-01

Radiation hardened linear devices are characterized for performance in combined total dose and displacement damage environments for a mission scenario with a high radiation level. Performance at low and high dose rate for both biased and unbiased conditions is compared and the impact to hardness assurance methodology is discussed.

Mutagenic adaptive response to high-LET radiation in human lymphoblastoid cells exposed to X-rays.

Science.gov (United States)

Varès, Guillaume; Wang, Bing; Tanaka, Kaoru; Kakimoto, Ayana; Eguchi-Kasai, Kyomi; Nenoi, Mitsuru

2011-01-10

The ability of cells to adapt low-dose or low-dose rate radiation is well known. High-LET radiation has unique characteristics, and the data concerning low doses effects and high-LET radiation remain fragmented. In this study, we assessed in vitro the ability of low doses of X-rays to induce an adaptive response (AR) to a subsequent challenging dose of heavy-ion radiation. Lymphoblastoid cells (TK6, AHH-1, NH32) were exposed to priming 0.02-0.1Gy X-rays, followed 6h later by challenging 1Gy heavy-ion radiation (carbon-ion: 20 and 40keV/μm, neon-ion: 150keV/μm). Pre-exposure of p53-competent cells resulted in decreased mutation frequencies at hypoxanthine-guanine phosphoribosyl transferase locus and different H2AX phosphorylation kinetics, as compared to cells exposed to challenging radiation alone. This phenomenon did not seem to be linked with cell cycle effects or radiation-induced apoptosis. Taken together, our results suggested the existence of an AR to mutagenic effects of heavy-ion radiation in lymphoblastoid cells and the involvement of double-strand break repair mechanisms. Copyright © 2010 Elsevier B.V. All rights reserved.

PARP-1 is a key player in controlling apoptosis induced by high LET carbon ion beam and low LET gamma radiation in HeLa cells

International Nuclear Information System (INIS)

Ghorai, Atanu; Ghosh, Utpal; Bhattacharyya, Nitai P.; Sarma, Asitikantha

2014-01-01

PARP-1 inhibitors have long been used as chemo-sensitizer or radio-sensitizer and specific PARP-1 inhibitors are also in clinical trial for the treatment of various cancers. PARP-1 is not only involved in DNA repair but also plays very complex role in induction of apoptosis in postirradiation condition. Our objective is to investigate role of PARP-1 in apoptosis triggered by high LET carbon ion beam (CIB) and low LET gamma. We have treated HeLa and PARP-1 knock down HeLa (Hsil) cells with various doses of CIB and gamma. We measured DNA damage by comet assay and various apoptotic parameters such as nuclear fragmentation, activation of caspase-3,8,9, AIF translocation etc. We observed higher DNA breaks and also higher apoptosis in HsiI cells compared with HeLa cells. Both CIB and gamma treatment results G2/M arrest but unlike gamma CIB makes S-phase delay, implicating that gamma and CIB triggers different pathway after DNA damage. Cell death by CIB or by gamma increased up on knocking down of PARP-1 but increase is higher for high LET CIB compared with low LET gamma. Furthermore, expression level of PARP-1 controls the intensity of overall apoptosis in cells in post-irradiation condition. So, combination of PARP-1 inhibition with high LET CIB could be a promising tool to combat cancer. (author)

Gene-expression profiling of Saccharomyces cerevisiae irradiated by high-LET radiations

Data.gov (United States)

National Aeronautics and Space Administration — Ionizing radiations are categorized by linear energy transfer (LET) into low-LET and high-LET. High-LET is considered to have a higher relative biological...

Neutron dose equivalent next to the target shield of a neutron therapy facility using an LET counter

International Nuclear Information System (INIS)

Stinchcomb, T.G.; Kuchnir, F.T.

1981-01-01

The use of a spherical tissue-equivalent proportional counter for measurements of the lineal energy (y) and derivations of the linear energy transfer (LET) for fast neutrons has the advantage of giving distributions of dose and dose equivalent as functions of either LET or y. A measurement next to the target shielding of the neutron therapy facility at the University of Chicago Hospitals and Clinics (UCHC) is described, and the data processing is outlined. The distributions are presented and compared to those from measurements in the neutron beam. The average quality factors are presented

Measurement and protection of the oxidative damage induced by high-LET carbon-ion irradiation in salmon sperm DNA solution

International Nuclear Information System (INIS)

Moritake, T.; Nose, T.; Tsuboi, K.; Anzai, K.; Ikota, N.; Ozawa, T.; Ando, K.

2003-01-01

The aims of this study are to quantify the yield of hydroxyl radicals (OH) , and to evaluate the oxidative damage on DNA after high-linear energy transfer (LET) carbon-ion beams and x-rays. For this purpose, the relationship between the radiolytic yield of OH in aqueous solution and 8-hydroxydeoxyguanosine (8-OHdG) level in DNA solution were assessed after radiation. In addition, the anti-oxidative effect of 3-methyl-1-phenyl-2-pyrazonline-5-one (edaravone) on DNA was evaluated. Culture medium containing 200 mM 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was irradiated with doses of 0 to 20 Gy with an LET of 20 to 90 keV/μm, and the yields of OH were measured using an electron spin resonance (ESR) spectrometer. Salmon sperm DNA solution at a concentration of 1.0 mg/ml was irradiated with 10 Gy of x-rays or 290 MeV/nucleon carbon-ion beams with an LET range of 20-80 keV/μm. 8-OHdG levels in the DNA solution were measured by HPLC with an electrochemical detector (ECD) after each irradiation. Edaravone was added to the DNA solution in final concentrations of 10 μM to 1 mM and 8-OHdG levels were measured by the same method after irradiation. The yield of OH by carbon-ion radiolysis increased in proportion to the absorbed dose over the range of 0 to 20 Gy, and the yield of OH decreased as LET increased logarithmically from 20 to 90 keV/μm. The level of 8-OHdG increased dose-dependently after x-ray irradiation, and it was significantly suppressed by edaravone. Furthermore, the yield of 8-OHdG and the protection efficiency by edaravone decreased as LET value increased. These unique findings provide further understanding of the indirect effect of high-LET radiation, and chemical protection of oxidative damage on DNA is important for clinical application of high-LET radiation

Measurement and protection of the oxidative damage induced by high-LET carbon-ion irradiation in salmon sperm DNA solution

Energy Technology Data Exchange (ETDEWEB)

Moritake, T; Nose, T [University of Tsukuba, (Japan); Tsuboi, K [Institute of Clinical Medical Center, (Japan); Anzai, K; Ikota, N [National Institute of Radiological Sciences, (Japan); Ozawa, T [Redox Regulation Research Group, (Japan); Ando, K [Research Center of Charged Particle Therapy, (Japan). National Institution

2003-07-01

The aims of this study are to quantify the yield of hydroxyl radicals (OH) , and to evaluate the oxidative damage on DNA after high-linear energy transfer (LET) carbon-ion beams and x-rays. For this purpose, the relationship between the radiolytic yield of OH in aqueous solution and 8-hydroxydeoxyguanosine (8-OHdG) level in DNA solution were assessed after radiation. In addition, the anti-oxidative effect of 3-methyl-1-phenyl-2-pyrazonline-5-one (edaravone) on DNA was evaluated. Culture medium containing 200 mM 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was irradiated with doses of 0 to 20 Gy with an LET of 20 to 90 keV/{mu}m, and the yields of OH were measured using an electron spin resonance (ESR) spectrometer. Salmon sperm DNA solution at a concentration of 1.0 mg/ml was irradiated with 10 Gy of x-rays or 290 MeV/nucleon carbon-ion beams with an LET range of 20-80 keV/{mu}m. 8-OHdG levels in the DNA solution were measured by HPLC with an electrochemical detector (ECD) after each irradiation. Edaravone was added to the DNA solution in final concentrations of 10 {mu}M to 1 mM and 8-OHdG levels were measured by the same method after irradiation. The yield of OH by carbon-ion radiolysis increased in proportion to the absorbed dose over the range of 0 to 20 Gy, and the yield of OH decreased as LET increased logarithmically from 20 to 90 keV/{mu}m. The level of 8-OHdG increased dose-dependently after x-ray irradiation, and it was significantly suppressed by edaravone. Furthermore, the yield of 8-OHdG and the protection efficiency by edaravone decreased as LET value increased. These unique findings provide further understanding of the indirect effect of high-LET radiation, and chemical protection of oxidative damage on DNA is important for clinical application of high-LET radiation.

Effects of estrogen and gender on cataractogenesis induced by high-LET radiation

International Nuclear Information System (INIS)

Henderson, M.A.; Rusek, A.; Valluri, S.; Garrett, J.; Lopez, J.; Caperell-Grant, A.; Mendonca, M.; Bigsby, R.; Dynlacht, J.

2010-01-01

Planning for long-duration manned lunar and interplanetary missions requires an understanding of radiation-induced cataractogenesis. Previously, it was demonstrated that low-linear energy transfer (LET) irradiation with 10 Gy of 60 Co γ rays resulted in an increased incidence of cataracts in male rats compared to female rats. This gender difference was not due to differences in estrogen, since male rats treated with the major secreted estrogen 17-β-estradiol (E2) showed an identical increase compared to untreated males. We now compare the incidence and rate of progression of cataracts induced by high-LET radiation in male and female Sprague-Dawley rats. Rats received a single dose of 1 Gy of 600 MeV 56 Fe ions. Lens opacification was measured at 2-4 week intervals with a slit lamp. The incidence and rate of progression of radiation-induced cataracts was significantly increased in the animals in which estrogen was available from endogenous or exogenous sources. Male rats with E2 capsules implanted had significantly higher rates of progression compared to male rats with empty capsules implanted (P = 0.025) but not compared to the intact female rats. These results contrast with data obtained after low-LET irradiation and suggest the possibility that the different types of damage caused by high- and low-LET radiation may be influenced differentially by steroid sex hormones.

Tri-P-LETS: Changing the Face of High School Computer Science

Science.gov (United States)

Sherrell, Linda; Malasri, Kriangsiri; Mills, David; Thomas, Allen; Greer, James

2012-01-01

From 2004-2007, the University of Memphis carried out the NSF-funded Tri-P-LETS (Three P Learning Environment for Teachers and Students) project to improve local high-school computer science curricula. The project reached a total of 58 classrooms in eleven high schools emphasizing problem solving skills, programming concepts as opposed to syntax,…

Biomarkers specific to densely-ionising (high LET) radiations

International Nuclear Information System (INIS)

Brenner, D.J.; Okladnikova, N.; Hande, P.; Burak, L.; Geard, C.R.; Azizova, T.

2001-01-01

There have been several suggestions of biomarkers that are specific to high LET radiation. Such a biomarker could significantly increase the power of epidemiological studies of individuals exposed to densely-ionising radiations such as alpha particles (e.g. radon, plutonium workers, individuals exposed to depleted uranium) or neutrons (e.g. radiation workers, airline personnel). We discuss here a potentially powerful high LET biomarker (the H value) which is the ratio of induced inter-chromosomal aberrations to intra-arm aberrations. Both theoretical and experimental studies have suggested that this ratio should differ by a factor of about three between high LET radiation and any other likely clastogen, and will yield more discrimination than the previously suggested F value (ratio of inter-chromosomal aberrations to intra-chromosomal inter-arm aberrations). Evidence of the long-term stability of such chromosomal biomarkers has also been generated. Because these stable intra-arm and inter-chromosomal aberrations are (1) frequent and (2) measurable at long times after exposure, this H value appears to be a practical biomarker of high LET exposure, and several in vitro studies have confirmed the approach for unstable aberrations. The approach is currently being tested in a population of Russian radiation workers exposed several decades ago to high- or low LET radiation. (author)

Total skin high-dose-rate electron therapy dosimetry using TG-51

International Nuclear Information System (INIS)

Gossman, Michael S.; Sharma, Subhash C.

2004-01-01

An approach to dosimetry for total skin electron therapy (TSET) is discussed using the currently accepted TG-51 high-energy calibration protocol. The methodology incorporates water phantom data for absolute calibration and plastic phantom data for efficient reference dosimetry. The scheme is simplified to include the high-dose-rate mode conversion and provides support for its use, as it becomes more available on newer linear accelerators. Using a 6-field, modified Stanford technique, one may follow the process for accurate determination of absorbed dose

Distributions of Low- and High-LET Radiation-Induced Breaks in Chromosomes are Associated with Inter- and Intrachromosome Exchanges

Science.gov (United States)

Hada, Megumi; Zhang, Ye; Feiveson, Alan; Cucinotta, Francis A.; Wu, Honglu

2010-01-01

To study the breakpoint along the length of the chromosome induced by low- and high-LET radiations, we exposed human epithelial cells in vitro to Cs-137 rays at both low and high dose rates, secondary neutrons at a low dose rate, and 600 MeV/u Fe ions at a high dose rate. The location of the breaks was identified using the multicolor banding in situ hybridization (mBAND) that paints Chromosome 3 in 23 different colored bands. The breakpoint distributions were found to be similar between rays of low and high dose rates and between the two high-LET radiation types. Detailed analysis of the chromosome break ends involved in inter- and intrachromosome exchanges revealed that only the break ends participating in interchromosome exchanges contributed to the hot spots found for low-LET. For break ends participating in intrachromosome exchanges, the distributions for all four radiation scenarios were similar with clusters of breaks found in three regions. Analysis of the locations of the two break ends in Chromosome 3 that joined to form an intrachromosome exchange demonstrated that two breaks with a greater genomic separation may be more likely to rejoin than two closer breaks, indicating that chromatin folding can play an important role in the rejoining of chromosome breaks. Our study demonstrated that the gene-rich regions do not necessarily contain more breaks. The breakpoint distribution depends more on the likelihood that a break will join with another break in the same chromosome or in a different chromosome.

LET and dose rate effect on radiation-induced copolymerization of maleimide with styrene in 2-propanol solution

Energy Technology Data Exchange (ETDEWEB)

Nakagawa, Seiko, E-mail: Nakagawa.Seiko@iri-tokyo.jp [Tokyo Metropolitan Industrial Technology Research Institute, 2-4-10 Aoumi, Koto-ku, Tokyo 135-0064 (Japan); Taguchi, Mitsumasa; Kimura, Atsushi [Environmental Radiation Processing Group, Environment and Industrial Materials Research Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)

2011-11-15

N{sub 2}-saturated 2-propanol solutions containing styrene and maleimide were irradiated by electron, proton, He and C-ion beams. The styrene-maleimide copolymer was produced by radical polymerization induced during irradiation. The effects of the radical distribution, which depends on the LET or dose rate, on the molecular weight and the polymer yield were discussed. - Highlights: > Maleimide with styrene in N{sub 2}-saturated 2-propanol was irradiated by electron and heavy ions. > LET and dose rate effects of radical polymerization induced by irradiation were studied. > Results have shown the relation between radical distribution and efficiency of polymerization.

Safety aspects of preoperative high-dose glucocorticoid in primary total knee replacement

DEFF Research Database (Denmark)

Jørgensen, C C; Pitter, F T; Kehlet, H

2017-01-01

Background: Preoperative single high-dose glucocorticoid may have early outcome benefits in total hip arthroplasty (THA) and knee arthroplasty (TKA), but long-term safety aspects have not been evaluated. Methods: From October 2013, the departments reporting to the prospective Lundbeck Foundation....... Conclusions: In this detailed prospective cohort study, preoperative high-dose glucocorticoid administration was not associated with LOS >4 days, readmissions or infectious complications in TKA patients without contraindications....

Precise let-7 expression levels balance organ regeneration against tumor suppression

Science.gov (United States)

Wu, Linwei; Nguyen, Liem H; Zhou, Kejin; de Soysa, T Yvanka; Li, Lin; Miller, Jason B; Tian, Jianmin; Locker, Joseph; Zhang, Shuyuan; Shinoda, Gen; Seligson, Marc T; Zeitels, Lauren R; Acharya, Asha; Wang, Sam C; Mendell, Joshua T; He, Xiaoshun; Nishino, Jinsuke; Morrison, Sean J; Siegwart, Daniel J; Daley, George Q; Shyh-Chang, Ng; Zhu, Hao

2015-01-01

The in vivo roles for even the most intensely studied microRNAs remain poorly defined. Here, analysis of mouse models revealed that let-7, a large and ancient microRNA family, performs tumor suppressive roles at the expense of regeneration. Too little or too much let-7 resulted in compromised protection against cancer or tissue damage, respectively. Modest let-7 overexpression abrogated MYC-driven liver cancer by antagonizing multiple let-7 sensitive oncogenes. However, the same level of overexpression blocked liver regeneration, while let-7 deletion enhanced it, demonstrating that distinct let-7 levels can mediate desirable phenotypes. let-7 dependent regeneration phenotypes resulted from influences on the insulin-PI3K-mTOR pathway. We found that chronic high-dose let-7 overexpression caused liver damage and degeneration, paradoxically leading to tumorigenesis. These dose-dependent roles for let-7 in tissue repair and tumorigenesis rationalize the tight regulation of this microRNA in development, and have important implications for let-7 based therapeutics. DOI: http://dx.doi.org/10.7554/eLife.09431.001 PMID:26445246

RBE-LET relationships of high-LET radiations in drosophila mutations

International Nuclear Information System (INIS)

Yoshikawa, Isao; Takatsuji, Toshihiro; Nagano, Masaaki; Takada, Jun; Endo, Satoru; Hoshi, Masaharu

1999-01-01

The relative biological effectiveness (RBE) of 252 Cf neutrons and synchrotron-generated high-energy charged particles for mutation induction was evaluated as a function of linear energy transfer (LET), using the loss of heterozygosity for wing-hair mutations and the reversion of the mutant white-ivory eye-color in Drosophila melanogaster. Loss of heterozygosity for wing-hair mutations results predominantly from mitotic crossing over induced in wing anlage cells of larvae, while the reverse mutation of eye-color is due to an intragenic structural change (2.96 kb-DNA excision) in the white locus on the X-chromosome. The measurements were performed in a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-color clone can be detected simultaneously in the same individual. Larvae were irradiated at the age of 3 days post oviposition with 252 Cf neutrons, carbon beam or neon beam. For the neutron irradiation, the RBE values for wing-hair mutations were larger than that for eye-color mutation by about 7 fold. The RBE of carbon ions for producing the wing-hair mutations increased with increase in LET. The estimated RBE values were found to be in the range 2 to 6.5 for the wing-hair. For neon beam irradiation, the RBE values for wing-hair mutations peak near 150 keV/μm and decrease with further increase in LET. On the other hand, the RBE values for the induction of the eye-color mutation are nearly unity in 252 Cf neutrons and both ions throughout the LET range irradiated. We discuss the relationships between the initial DNA damage and LET in considering the mechanism of somatic mutation induction. (author)

Special photographic emulsions for high LET dosimetry

International Nuclear Information System (INIS)

Katz, R.

1978-12-01

The purpose of these investigations into photographic emulsion dosimetry is to attempt to use the photographic emulsion to mimic the response of human tissues to high LET radiations. The program therefore requires that a systematic understanding of the response of mammalian cells to ionizing radiations be achieved. We have been concerned with differences in RBE and in radiation response to both high and LET radiations, and in the interrelationship between observations with these different radiations

A Review: Some biological effects of high LET radiations

Science.gov (United States)

Wiley, A., Jr.

1972-01-01

There are qualitative and quantitative differences in the biological damage observed after exposure to high LET radiation as compared to that caused by low LET radiations. This review is concerned with these differences, which are ultimately reflected at the biochemical, cellular and even whole animal levels. In general, high LET radiations seem to produce biochemical damage which is more severe and possibly less repairable. Experimental data for those effects are presented in terms of biochemical RBE's with consideration of both early and late manifestations. An LET independent process by which significant biochemical damage may result from protons, neutrons and negative pion mesons is discussed.

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

Energy Technology Data Exchange (ETDEWEB)

Scott, Bobby, R., Ph.D.

2003-06-27

radiation). Such phantom risks also may arise from risk assessments conducted for combined exposure to low- and high-LET radiations when based on the LNT or other models that exclude RR < 1. Our results for high-LET radiation are consistent with the LNT hypothesis but only where there is no additional low-LET contribution (e.g., gamma rays) to the total dose. For high-LET neutron sources, gamma rays arise (especially in vivo) for large mammals such as humans from neutron interactions with tissue. The gamma rays might provide some protection from low-dose-related stochastic effects via inducing the protective bystander apoptosis effect that is considered to contribute to tissue cleansing via removal of problematic cells.

Fractionated dose skews differentiation of Glial progenitor cells into immature oligodendrocytes and astrocytes, with lower mature oligodendrocytes formation, as compared to singe low dose of low and high LET radiation

International Nuclear Information System (INIS)

Sanchez, Zina; Pena, Louis; Naidu, Mamta

2010-01-01

In the proposed study, the effect of fractionated, low dose versus single low dose of low LET X-rays and charged particles on induction of base excision repair enzyme Apurinic Endonuclease-1 (Ape1) are determined, which is known to inhibit cell differentiation, and found that at lower doses of 10,25 and 50 cGy there was a very significant induction of Apel which correlated to number of fractions, whereas at 100 cGy this induction was significantly lower. Also, there was a clear correlation between increase in fractions and higher immature OL and astrocyte formation

Proton dose distribution measurements using a MOSFET detector with a simple dose‐weighted correction method for LET effects

Science.gov (United States)

Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-01-01

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth‐dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high‐bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L‐shaped bolus. The dose reproducibility, angular dependence and depth‐dose response were evaluated using a 190 MeV proton beam. Depth‐output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose‐weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L‐shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors. PACS number: 87.56.‐v

Mutagenic effect of radiations of various LET on Salmonella cells

International Nuclear Information System (INIS)

Kozubek, S.; Krasavin, E.A.; Amirtaev, K.G.; Tokarova, B.; Basha, S.G.

1989-01-01

Regularities of mutagenic effect of heavy charged particles of helium, deuterium ions and protons on various strains of Salmonella typhimurium were studied. Linear dose dependences of mutation frequency in the range of low doses were revealed. A conclusion was made that mutation process at low dose irradiation is determined in various teststrains of Salmonella typhimurium by certain premutation injuries. Quite a different picture is observed in mutation process in case of high dose irradiation where effect of inducible SOS-repair is distinctly manifested. Not only spectra of primary DNA injuries but probability of their fixation into mutation can change with the increase of LET. If fixation probability doesn't change with LET increase for replicative mutagenesis which make basis contribution to linear component of dose dependence of mutation frequency the probability of fixation is increased for reparative mutagenesis. It accounts for increase of values of relative genetic efficiency with LET increase. 7 refs.; 6 figs.; 1 tab

Dependence of total dose response of bipolar linear microcircuits on applied dose rate

International Nuclear Information System (INIS)

McClure, S.; Will, W.; Perry, G.; Pease, R.L.

1994-01-01

The effect of dose rate on the total dose radiation hardness of three commercial bipolar linear microcircuits is investigated. Total dose tests of linear bipolar microcircuits show larger degradation at 0.167 rad/s than at 90 rad/s even after the high dose rate test is followed by a room temperature plus a 100 C anneal. No systematic correlation could be found for degradation at low dose rate versus high dose rate and anneal. Comparison of the low dose rate with the high dose rate anneal data indicates that MIL-STD-883, method 1019.4 is not a worst-case test method when applied to bipolar microcircuits for low dose rate space applications

Numerical simulation of a TLD pulsed laser-heating scheme for determination of shallow dose and deep dose in low-LET radiation fields

International Nuclear Information System (INIS)

Kearfott, K.J.; Han, S.; Wagner, E.C.; Samei, E.; Wang, C.-K.C.

2000-01-01

A new method is described to determine the depth-dose distribution in low-LET radiation fields using a thick thermoluminescent dosimeter (TLD) with a pulsed laser-heating scheme to obtain TL glow output. The computational simulation entails heat conduction and glow curve production processes. An iterative algorithm is used to obtain the dose distribution in the detector. The simulation results indicate that the method can predict the shallow and deep dose in various radiation fields with relative errors less than 20%

WE-H-BRA-05: Investigation of LET Spectral Dependence of the Biological Effects of Therapeutic Protons

Energy Technology Data Exchange (ETDEWEB)

Guan, F; Bronk, L; Kerr, M; Wang, X; Li, Y; Peeler, C; Sahoo, N; Patel, D; Mirkovic, D; Titt, U; Grosshans, D; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: To investigate the dependence of biologic effect (BE) of therapeutic protons on LET spectra by comparing BEs with equal dose-averaged LET (LETd) derived from different LET spectra using high-throughput in vitro clonogenic survival assays. Methods: We used Geant4 to design the relevant experimental setups and perform the dose, LETd, and LET spectra calculations for spot-scanning protons. The clonogenic assay was performed using the H460 lung cancer cell line cultured in 96-well plates. In the first experimental setup (S1), cells were irradiated using 127.4 MeV protons with a 93.22 mm Lucite buildup resulting in a LETd value of 3.4 keV/µm in the cell layer. In the second experimental setup (S2), cells were irradiated by a combination of 127.4 MeV and 136.4 MeV protons with a 96.61 mm Lucite buildup. The LETd values in the cell layer were 11.4 keV/µm and 1.5 keV/µm respectively, but an average LETd of 3.4 keV/µm was obtained by adjusting the relative fluence of each beam. Ten discrete dose levels with 0.5 Gy increments were delivered. Results: In the two setups, the energies or LET spectra were different but resulted in identical LETd values. We quantified the dose contributions from high-LET (≥10 keV/µm, threshold determined by previous experiments) events in the LET spectra separately for these two setups as 3.2% and 10.5%. The biologic effects at each identical dose level yielded statistically significant different survival curves (extra sum-of-squares F-test, P<0.0001). The second setup with a higher contribution from high-LET events exhibited the higher biologic effect with a dose enhancement factor of 1.17±0.03 at 0.10 surviving fraction. Conclusion: The dose-averaged LET may not be an accurate indicator of the biological effects of protons. Detailed LET spectra may need to be considered explicitly to accurately quantify the biologic effects of protons. Funding Support: U19 CA021239-35, R21 CA187484-01 and MDACC-IRG.

Dose measurements and LET-determination in space station MIR during the Russian long term flight RLF

International Nuclear Information System (INIS)

Vana, N.; Schoener, N.; Fugger, M.; Akatov, Y.; Shurshakov, V.

1996-01-01

For determination of the absorbed dose and the dose equivalent in complex mixed radiation fields, new methods were developed in the frame of the Austrian-Soviet space mission AUSTROMIR in October 1991. The method utilizes the changes of peak height ratios in thermoluminescence glowcurves. Peak height ratios depend on the linear energy transfer (LET) of absorbed radiation. This effect was calibrated in different radiation fields (alpha-, beta-, gamma-, neutron fields and heavy charged particle beams). The method was approached for dose measurements during several space programs (DOSIMIR, BION-10, PHOTONS). During the Russian long term flight RLF six dosemeter packets were exposed in three different periods. Two positions with different shielding (the working area and the cabin of the board engineer) were chosen for the exposition of the dosemeters during each period in order to measure the variation of absorbed dose as well as the variation of average LET of absorbed radiation within the habitable part of space station MIR. These results will be compared with the results during two former periods of measurements on space station MIR (AUSTROMIR/DOSIMIR) and results obtained inside of biosatellite BION-10 and during the space shuttle mission STS-60. (author)

Imaging Features that Discriminate between Foci Induced by High-and Low-LET Radiation in Human Fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Costes, Sylvain V.; Boissiere, Arnaud; Ravani, Shraddha; Romano,Raquel; Parvin, Bahram; Barcellos-Hoff, Mary Helen

2006-10-08

In this study, we investigated the formation ofradiation-induced foci in normal human fibroblasts exposed to X rays or130 keV/mum nitrogen ions using antibodies to phosphorylated proteinkinase ataxia telangiectasia mutated (ATMp) and histone H2AX(gamma-H2AX). High-content automatic image analysis was used to quantifythe immunofluorescence of radiation-induced foci. The size ofradiation-induced foci increased for both proteins over a 2-h periodafter nitrogen-ion irradiation, while the size of radiation-induced focidid not change after exposure to low-LET radiation. The number ofradiation-induced ATMp foci showed a more rapid rise and greaterfrequency after X-ray exposure and was resolved more rapidly such thatthe frequency of radiation-induced foci decreased by 90 percent comparedto 60 percent after exposure to high-LET radiation 2 h after 30 cGy. Incontrast, the kinetics of radiation-induced gamma-H2AX focus formationwas similar for high- and low-LET radiation in that it reached a plateauearly and remained constant for up to 2 h. High-resolution 3D images ofradiation-induced gamma-H2AX foci and dosimetry computation suggest thatmultiple double-strand breaks from nitrogen ions are encompassed withinlarge nuclear domains of 4.4 Mbp. Our work shows that the size andfrequency of radiation-induced foci vary as a function of radiationquality, dose, time and protein target. Thus, even though double-strandbreaks and radiation-induced foci are correlated, the dynamic nature ofboth contradicts their accepted equivalence for low doses of differentradiation qualities.

In vitro RBE-LET dependence for multiple particle types

DEFF Research Database (Denmark)

Sørensen, Brita Singers; Overgaard, Jens; Bassler, Niels

2011-01-01

Background. In vitro RBE values for various high LET radiation types have been determined for many different cell types. Occasionally it is criticized that RBE for a given endpoint cannot be single-value dependent on LET alone, but also on particle species, due to the different dose deposition...... profiles on microscopic scale. Hence LET is not sufficient as a predictor of RBE, and this is one of the motivations for development of radiobiological models which explicitly depend on the detailed particle energy spectrum of the applied radiation field. The aim of the present study is to summarize...... the available data in the literature regarding the dependency of RBE on LET for different particles. Method. As RBE is highly dependent on cell type and endpoint, we discriminated the RBE-LET relationship for the three investigated cell lines and at the same endpoint (10% survival in colony formation). Data...

Cancer and low dose responses in vivo: implications for radiation protection

International Nuclear Information System (INIS)

Mitchel, R.E.J.

2006-01-01

Full text: Radiation protection practices assume that cancer risk is linearly proportional to total dose, without a threshold, both for people with normal cancer risk and for people who may be genetically cancer prone. Mice heterozygous for the Tp 53 gene are cancer prone, and their increased risk from high doses was not different from Tp 53 normal mice. However, in either Tp 53 normal or heterozygous mice, a single low dose of low LET radiation given at low dose rate protected against both spontaneous and radiation-induced cancer by increasing tumor latency. Increased tumor latency without a cancer frequency change implies that low doses in vivo primarily slow the process of genomic instability, consistent with the elevated capacity for correct DSB rejoining seen in low dose exposed cells. The in vivo animal data indicates that, for low doses and low dose rates in both normal and cancer prone adult mice, risk does not increase linearly with dose, and dose thresholds for increased risk exist. Below those dose thresholds (which are influenced by Tp 53 function) overall risk is reduced below that of unexposed control mice, indicating that Dose Rate Effectiveness Factors (DREF) may approach infinity, rather than the current assumption of 2. However, as dose decreases, different tissues appear to have different thresholds at which detriment turns to protection, indicating that individual tissue weighting factors (Wt) are also not constant, but vary from positive values to zero with decreasing dose. Measurements of Relative Biological Effect between high and low LET radiations are used to establish radiation weighting factors (Wr) used in radiation protection, and these are also assumed to be constant with dose. However, since the risk from an exposure to low LET radiation is not constant with dose, it would seem unlikely that radiation-weighting factors for high LET radiation are actually constant at low dose and dose rate

High LET radiation and mechanism of DNA damage repair

International Nuclear Information System (INIS)

Furusawa, Yoshiya

2004-01-01

Clarifying the mechanism of repair from radiation damage gives most important information on radiation effects on cells. Approximately 10% of biological experiments groups in Heavy Ion Medical Accelerator in Chiba (HIMAC) cooperative research group has performed the subject. They gave a lot of new findings on the mechanism, and solved some open questions. The reason to show the peak of relative biological effectiveness RBE at around 100-200 keV/μm causes miss-repair of DNA damage. Sub-lethal damage generated by high linear energy transfer (LET) radiation can be repaired fully. Potentially lethal damages by high-LET radiation also repaired, but the efficiency decreased with the LET, and so on. (author)

Calculated LET-Spectrum of Antiprotons

DEFF Research Database (Denmark)

Bassler, Niels

-LET components resulting from the annihilation. Though, the calculations of dose-averaged LET in the entry region may suggest that the RBE of antiprotons in the plateau region could significantly differ from unity. Materials and Methods Monte Carlo simulations using FLUKA were performed for calculating...

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

International Nuclear Information System (INIS)

Lee, S.K.

1998-01-01

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

The concept of average LET values determination

International Nuclear Information System (INIS)

Makarewicz, M.

1981-01-01

The concept of average LET (linear energy transfer) values determination, i.e. ordinary moments of LET in absorbed dose distribution vs. LET of ionizing radiation of any kind and any spectrum (even the unknown ones) has been presented. The method is based on measurement of ionization current with several values of voltage supplying an ionization chamber operating in conditions of columnar recombination of ions or ion recombination in clusters while the chamber is placed in the radiation field at the point of interest. By fitting a suitable algebraic expression to the measured current values one can obtain coefficients of the expression which can be interpreted as values of LET moments. One of the advantages of the method is its experimental and computational simplicity. It has been shown that for numerical estimation of certain effects dependent on LET of radiation it is not necessary to know the dose distribution but only a number of parameters of the distribution, i.e. the LET moments. (author)

Imaging Features that Discriminate between Foci Induced by High- and Low-LET Radiation in Human Fibroblasts

International Nuclear Information System (INIS)

Costes, Sylvain V.; Boissiere, Arnaud; Ravani, Shraddha; Romano, Raquel; Parvin, Bahram; Barcellos-Hoff, Mary Helen

2006-01-01

In this study, we investigated the formation of radiation-induced foci in normal human fibroblasts exposed to X rays or 130 keV/mum nitrogen ions using antibodies to phosphorylated protein kinase ataxia telangiectasia mutated (ATMp) and histone H2AX(gamma-H2AX). High-content automatic image analysis was used to quantify the immunofluorescence of radiation-induced foci. The size of radiation-induced foci increased for both proteins over a 2-h period after nitrogen-ion irradiation, while the size of radiation-induced foci did not change after exposure to low-LET radiation. The number of radiation-induced ATMp foci showed a more rapid rise and greater frequency after X-ray exposure and was resolved more rapidly such that the frequency of radiation-induced foci decreased by 90 percent compared to 60 percent after exposure to high-LET radiation 2 h after 30 cGy. In contrast, the kinetics of radiation-induced gamma-H2AX focus formation was similar for high- and low-LET radiation in that it reached a plateau early and remained constant for up to 2 h. High-resolution 3D images of radiation-induced gamma-H2AX foci and dosimetry computation suggest that multiple double-strand breaks from nitrogen ions are encompassed within large nuclear domains of 4.4 Mbp. Our work shows that the size and frequency of radiation-induced foci vary as a function of radiation quality, dose, time and protein target. Thus, even though double-strand breaks and radiation-induced foci are correlated, the dynamic nature of both contradicts their accepted equivalence for low doses of different radiation qualities

LET calibration for CR-39 detectors in different oxygen environments

International Nuclear Information System (INIS)

Zhou, D.; Semones, E.; Weyland, M.; Benton, E.R.

2007-01-01

High LET (linear energy transfer) radiation is the main contributor to the radiation field in low Earth orbit (LEO) in terms of dose equivalent. CR-39 plastic nuclear track detectors (PNTDs) can measure the LET spectrum and charge spectrum for the complicated radiation field in space. Previous research indicated that the sensitivity of CR-39 is different for CR-39 PNTDs working in different oxygen environments. LET calibration for CR-39 detectors in different oxygen environments is needed. Almost all the previous LET calibration work was carried out for CR-39 detectors in good-oxygen condition, LET calibration work for CR-39 in poor-oxygen condition has not been conducted until our work. Systematic LET calibrations were carried out by JSC-SRAG (Space Radiation Analysis Group) for CR-39 detectors working in different oxygen environments and abundant results of LET calibrations were obtained. This paper introduces the method for CR-39 LET calibration, presents and discusses the calibration results and some applications

Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC1638N/+ mice

Science.gov (United States)

Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Fornace, Albert J.; Datta, Kamal

2017-05-01

Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses in excess of permissible limits with implications for colorectal carcinogenesis. Exposure to IR in outer space occurs at low doses and dose rates, and energetic heavy ions due to their high linear energy transfer (high-LET) characteristics remain a major concern for CRC risk in astronauts. Previously, we have demonstrated that intestinal tumorigenesis in a mouse model (APC1638N/+) of human colorectal cancer was significantly higher after exposure to high dose rate energetic heavy ions relative to low-LET γ radiation. The purpose of the current study was to compare intestinal tumorigenesis in APC1638N/+ mice after exposure to energetic heavy ions at high (50 cGy/min) and relatively low (0.33 cGy/min) dose rate. Male and female mice (6-8 weeks old) were exposed to either 10 or 50 cGy of 28Si (energy: 300 MeV/n; LET: 70 keV/μm) or 56Fe (energy: 1000 MeV/n; LET: 148 keV/μm) ions at NASA Space Radiation Laboratory in Brookhaven National Laboratory. Mice (n = 20 mice/group) were euthanized and intestinal and colon tumor frequency and size were counted 150 days after radiation exposure. Intestinal tumorigenesis in male mice exposed to 56Fe was similar for high and low dose rate exposures. Although male mice showed a decreasing trend at low dose rate relative to high dose rate exposures, the differences in tumor frequency between the two types of exposures were not statistically significant after 28Si radiation. In female mice, intestinal tumor frequency was similar for both radiation type and dose rates tested. In both male and female mice intestinal tumor size was not different after high and low dose rate radiation exposures. Colon tumor frequency in male and female mice after high and low dose rate energetic heavy ions was also not significantly different. In conclusion, intestinal and colonic tumor

WRAITH, Internal and External Doses from Atmospheric Release of Isotopes

International Nuclear Information System (INIS)

1984-01-01

1 - Description of problem or function: WRAITH calculates the atmospheric transport of radioactive material to each of a number of downwind receptor points and the external and internal doses to a reference man at each of the receptor points. 2 - Method of solution: The movement of the released material through the atmosphere is calculated using a bivariate straight-line Gaussian distribution model with Pasquill values for standard deviations. The quantity of material in the released cloud is modified during its transit time to account for radioactive decay and daughter production. External doses due to exposure to the cloud can be calculated using a semi-infinite cloud approximation or a 'finite plume' three-dimensional point-kernel numerical integration technique. Internal doses due to acute inhalation are calculated using the ICRP Task Group Model and a four-segmented gastro- intestinal tract model. Translocation of the material between body compartments and retention in the body compartments are calculated using multiple exponential retention functions. Internal doses to each organ are calculated as sums of cross-organ doses with each target organ irradiated by radioactive material in a number of source organs. All doses are calculated in rads with separate values determined for high-LET and low-LET radiation. 3 - Restrictions on the complexity of the problem: - Doses to only three target organs (total body, red bone marrow, and the lungs) are considered and acute inhalation is the only pathway for material to enter the body. The dose response model is not valid for high-LET radiation other than alphas. The high-LET calculation ignores the contributions of neutrons, spontaneous fission fragments, and alpha recoil nuclei

Estimation of lung tissue doses following exposure to low-LET radiation in the Canadian study of cancer following multiple fluoroscopies

International Nuclear Information System (INIS)

Howe, G.R.; Yaffe, M.

1992-02-01

Lung tissue doses from exposure to external low-LET radiation have been estimated for each year between 1930 and 1960 for 92,707 tuberculosis patients first treated in Canadian institutions between 1930 and 1952. Many of these patients received multiple chest fluoroscopies together with treatment by artificial pneumothorax, and thus accumulated doses up to 15.7 grays. The estimated doses have been used in a statistical analysis of lung cancer mortality between 1950 and 1987 occurring among 64,698 patients known to be alive at the start of 1950, and followed by linkage to the Canadian national mortality data base. There were substantial variations in the total cumulative lung tissue dose received by the cohort, with 2,490 individuals having doses in excess of 1.7 grays. A total of 1,156 lung cancer deaths was observed in the cohort, and these have been used to estimate relative risks. The most appropriate risk model appears to be a simple linear relative risk function, with an excess relative risk coefficient of 0.089 for an absorbed dose of 1 gray. This contrasts with estimates of relative risk based on the atomic bomb survivors study, for which the excess relative risk coefficient for males 20 years after the first exposure is estimated to be 0.64. The difference is statistically significant. It is postulated that fractionation and dose rate effectiveness factors may account for some of the discrepancy. (Modified author abstract) (14 refs., 20 tabs.)

Some thoughts on tolerance, dose, and fractionation in boron neutron capture therapy

International Nuclear Information System (INIS)

Gahbauer, R.; Goodman, J.; Blue, T.

1988-01-01

Unique to boron neutron capture therapy, the tolerance very strongly depends on the boron concentration in normal brain, skin and blood. If one first considers the ideal situation of a 2 KeV beam and a compound clearing from normal tissues and blood, the tolerance dose to epithermal beams relates to the maximum tolerated capture gamma dose and capture high LET dose, H (n,gamma)D and N(n,p) 14 C. The authors can relate this gamma and high LET dose to known clinical experience. Assuming gamma and high LET dose ratios as given by Fairchild and Bond, one may first choose a clearly safe high LET whole brain dose and calculate the unavoidably resulting gamma dose. To a first approximation 500 cGy of high LET dose results in 3,000 cGy gamma dose. One can speculate that this approximates the tolerance of whole brain to the 2 KeV beam with no contributing boron dose if the radiation is fractionated. It would clearly be beyond tolerance in a single fraction where most therapists would be uncomfortable to deliver even one third of the above doses

Biological fingerprint of high LET radiation. Brenner hypothesis

International Nuclear Information System (INIS)

Kodama, Yoshiaki; Awa, Akio; Nakamura, Nori

1997-01-01

Hypothesis by Brenner et al. (1994) that in chromosome aberrations in human peripheral lymphocytes induced by radiation exposure, F value (dicentrics/rings) differs dependently on the LET and can be a biomarker of high LET radiation like neutron and α-ray was reviewed and evaluated as follows. Radiation and chromosome aberrations; in this section, unstable aberrations like dicentric and rings (r) and stable ones like translocation and pericentric inversions were described. F value. Brenner hypothesis. Bauchinger's refutation. F value determined by FISH method; here, FISH is fluorescence in situ hybridization. F value in studies by author's Radiation Effect Research Facility. Frequency of chromosome aberration in A-bomb survivors and ESR (ESR: electron spin resonance). The cause for fluctuation of F values. The Brenner hypothesis could not be supported by studies by author's facility, suggesting that the rate of inter-chromosomal and intra-chromosomal exchange abnormalities can not be distinguishable by the radiation LET. This might be derived from the difference in detection technology of r rather than in LET. (K.H.)

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

International Nuclear Information System (INIS)

Spitz, Douglas R.

2009-01-01

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; O 2 - and H 2 O 2 ) as well as demonstrating increased sensitivity to low dose/low LET radiation (10 cGy) in cultured mammalian cells. Aim No.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 No.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

Gene conversion in yeast as a function of linear energy transfer (LET) for low-LET radiation

International Nuclear Information System (INIS)

Unrau, P.; Morrison, D.P.; Johnson, J.R.

1992-05-01

The relative biological effectiveness (RBE) for low-LET radiation is known to depend on such factors as LET and dose rate. Microdosimetric calculations indicate that the biological target size could also be an important parameter, and calculations predict that the RBE for effects produced by hits in target sizes below about 100 nm should be unity for all low LET radiation. We have measured that RBE for gene conversion in yeast (a small target) for five different low LET photon sources, and the results were consistent with an RBE of unity, which agrees with microdosimetric predictions. 4 refs

Low Dose Suppression of Neoplastic Transformation in Vitro

Energy Technology Data Exchange (ETDEWEB)

John Leslie Redpath

2012-05-01

This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

Apoptosis induced by high- and low-LET radiations

International Nuclear Information System (INIS)

Hendry, J.H.; Potten, C.S.; Merritt, A.

1995-01-01

Cell death after irradiation occurs by apoptosis in certain cell populations in tissues. The phenomenon also occurs after high linear energy transfer (LET) irradiation, and the relative biological effectiveness (RBE) is 3 to 4 (with respect to low-LET radiation and apoptosis in intestinal crypts) for neutrons with energies of 14 MeV and up to 600 MeV. It is thought that p53 plays a role in the phenomenon, as radiation-induced apoptosis is not observed in p53-null animals. (orig.)

Exploration of 'over kill effect' of high-LET Ar- and Fe-ions by evaluating the fraction of non-hit cell and interphase death

International Nuclear Information System (INIS)

Mehnati, P.; Sasaki, Hiroshi; Morimoto, Shigeko; Yatagai, Fumio; Hanaoka, Fumio; Furusawa, Yoshiya; Kanai, Tatsuaki; Kobayashi, Yasuhiko; Wada, Seiichi

2005-01-01

The reason why relative biological effectiveness (RBE) for cell killing fell to less than unity (1.0) with very high-linear energy transfer (LET) heavy-ions ( 40 Ar: 1,640 keV/μm; 56 Fe: 780, 1,200, 2,000 keV/μm) was explored by evaluating the fraction of non-hit cell (time-lapse observation) and cells undergoing interphase death (calculation based on our previous data). Chinese hamster ovary (CHO) cells were exposed to 4 Gy (30% survival dose) of Ar (1,640 keV/μm) or Fe-ions (2,000 keV/μm). About 20% of all cells were judged to be non-hit, and about 10% cells survived radiation damage. About 70% cells died after dividing at least once (reproductive death) or without dividing (interphase death). RBE for reproductive (RBE[R]) and interphase (RBE[I]) death showed a similar LET dependence with maximum around 200 keV/μm. In this LET region, at 30% survival level, about 10% non-survivors underwent interphase death. The corresponding value for very high-LET Fe-ions (2,000 keV/μm) was not particularly high (-15%), whereas that for X-rays was less than 3%. However, reproductive death (67%) predominated over interphase death (33%) even in regard to rather severely damaged cells (1% survival level) after exposure to Fe-ions (2,000 keV/μm). These indicate that interphase death is a type of cell death characteristic for the cells exposed to high-LET radiation and is not caused by 'cellular over kill effect'. Both NHF37 (non-hit fraction at 37% survival) and inactivation cross-section for reproductive death (σ[R]) began to increase when LET exceeded 100 keV/μm. The exclusion of non-hit fraction in the calculation of surviving fraction partially prevented the fall of RBE[R] when LET exceeded 200 keV/μm. On the other hand, the mean number of lethal damage per unit dose (NLD/Gy) showed the same LET-dependent pattern as RBE[R]. These suggest that the increase in non-hit fraction and σ[R] with an increasing LET is caused by enhanced clustering of ionization and DNA damage

Radiation-Induced Epigenetic Alterations after Low and High LET Irradiations

Energy Technology Data Exchange (ETDEWEB)

Aypar, Umut; Morgan, William F.; Baulch, Janet E.

2011-02-01

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding the delayed, non-targeted effects of radiation including radiationinduced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET x-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. MiRNA shown to be altered in expression level after x-ray irradiation are involved in chromatin remodeling and DNA methylation. Different and higher incidence of epigenetic changes were observed after exposure to low LET x-rays than high LET Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This study also shows that the irradiated cells acquire epigenetic changes even though they are chromosomally stable suggesting that epigenetic aberrations may arise in the cell without initiating RIGI.

Repair of skin damage during fractionated irradiation with gamma rays and low-LET carbon ions

International Nuclear Information System (INIS)

Ando, Koichi; Koike, Sachiko; Uzawa, Akiko; Takai, Nobuhiko; Fukawa, Takeshi; Furusawa, Yoshiya; Aoki, Mizuho; Hirayama, Ryoichi

2006-01-01

In clinical use of carbon-ion beams, a deep-seated tumor is irradiated with a Spread-Out Bragg peak (SOBP) with a high-linear energy transfer (LET) feature, whereas surface skin is irradiated with an entrance plateau, the LET of which is lower than that of the peak. The repair kinetics of murine skin damage caused by an entrance plateau of carbon ions was compared with that caused by photons using a scheme of daily fractionated doses followed by a top-up dose. Right hind legs received local irradiations with either 20 keV/μm carbon ions or γ rays. The skin reaction of the irradiated legs was scored every other day up to Day 35 using a scoring scale that consisted of 10 steps, ranging from 0.5 to 5.0. An isoeffect dose to produce a skin reaction score of 3.0 was used to obtain a total dose and a top-up dose for each fractionation. Dependence on a preceding dose and on the time interval of a top-up dose was examined using γ rays. For fractionated γ rays, the total dose linearly increased while the top-up dose linearly decreased with an increase in the number of fractions. The magnitude of damage repair depended on the size of dose per fraction, and was larger for 5.2 Gy than 12.5 Gy. The total dose of carbon ions with 5.2 Gy per fraction did not change till 2 fractions, but abruptly increased at the 3rd fraction. Factors such as rapid repopulation, induced repair and cell cycle synchronization are possible explanations for the abrupt increase. As an abrupt increase/decrease of normal tissue damage could be caused by changing the number of fractions in carbon-ion radiotherapy, we conclude that, unlike photon therapy, skin damage should be carefully studied when the number of fractions is changed in new clinical trials. (author)

Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial

DEFF Research Database (Denmark)

Lunn, Troels; Kristensen, Billy Bjarne; Andersen, Lasse

2011-01-01

Total knee arthroplasty (TKA) is associated with severe pain and inflammation despite an extensive multimodal analgesic approach, but the effect of high-dose glucocorticoid administration has not been studied.......Total knee arthroplasty (TKA) is associated with severe pain and inflammation despite an extensive multimodal analgesic approach, but the effect of high-dose glucocorticoid administration has not been studied....

Genotoxic Effects of Low- and High-LET Radiation on Human Epithelial Cells Grown in 2-D Versus 3-D Culture

Science.gov (United States)

Patel, Z. S.; Cucinotta, F. A.; Huff, J. L.

2011-01-01

Risk estimation for radiation-induced cancer relies heavily on human epidemiology data obtained from terrestrial irradiation incidents from sources such as medical and occupational exposures as well as from the atomic bomb survivors. No such data exists for exposures to the types and doses of high-LET radiation that will be encountered during space travel; therefore, risk assessment for space radiation requires the use of data derived from cell culture and animal models. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. This work compares the genotoxic effects of radiation on normal human epithelial cells grown in standard 2-D monolayer culture compared to 3-D organotypic co-culture conditions. These 3-D organotypic models mimic the morphological features, differentiation markers, and growth characteristics of fully-differentiated normal human tissue and are reproducible using defined components. Cultures were irradiated with 2 Gy low-LET gamma rays or varying doses of high-LET particle radiation and genotoxic damage was measured using a modified cytokinesis block micronucleus assay. Our results revealed a 2-fold increase in residual damage in 2 Gy gamma irradiated cells grown under organotypic culture conditions compared to monolayer culture. Irradiation with high-LET particle radiation gave similar results, while background levels of damage were comparable under both scenarios. These observations may be related to the phenomenon of "multicellular resistance" where cancer cells grown as 3-D spheroids or in vivo exhibit an increased resistance to killing by chemotherapeutic agents compared to the same cells grown in 2-D culture. A variety of factors are likely involved in mediating this process, including increased cell-cell communication, microenvironment influences, and changes in cell cycle kinetics that may promote survival of damaged cells in 3-D culture that would

mBAND analysis for high- and low-LET radiation-induced chromosome aberrations: A review

Energy Technology Data Exchange (ETDEWEB)

Hada, Megumi, E-mail: megumi.hada-1@nasa.gov [NASA Johnson Space Center, Houston, TX 77058 (United States); Universities Space Research Association, Houston, TX 77058 (United States); Wu Honglu; Cucinotta, Francis A. [NASA Johnson Space Center, Houston, TX 77058 (United States)

2011-06-03

During long-term space travel or cancer therapy, humans are exposed to high linear energy transfer (LET) energetic heavy ions. High-LET radiation is much more effective than low-LET radiation in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, and cytogenetic damage can be utilized as a biomarker for radiation insults. Epidemiological data, mainly from survivors of the atomic bomb detonations in Japan, have enabled risk estimation from low-LET radiation exposures. The identification of a cytogenetic signature that distinguishes high- from low-LET exposure remains a long-term goal in radiobiology. Recently developed fluorescence in situ hybridization (FISH)-painting methodologies have revealed unique endpoints related to radiation quality. Heavy-ions induce a high fraction of complex-type exchanges, and possibly unique chromosome rearrangements. This review will concentrate on recent data obtained with multicolor banding in situ hybridization (mBAND) methods in mammalian cells exposed to low- and high-LET radiations. Chromosome analysis with mBAND technique allows detection of both inter- and intrachromosomal exchanges, and also distribution of the breakpoints of aberrations.

Radiation-induced epigenetic alterations after low and high LET irradiations

International Nuclear Information System (INIS)

Aypar, Umut; Morgan, William F.; Baulch, Janet E.

2011-01-01

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise in the

Radiation-induced epigenetic alterations after low and high LET irradiations

Energy Technology Data Exchange (ETDEWEB)

Aypar, Umut, E-mail: uaypa001@umaryland.edu [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Morgan, William F. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Baulch, Janet E. [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

2011-02-10

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NF{kappa}B), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise

Comparison of CREME (cosmic-ray effects on microelectronics) model LET (linear energy transfer) spaceflight dosimetry data

Energy Technology Data Exchange (ETDEWEB)

Letaw, J.R.; Adams, J.H.

1986-07-15

The galactic cosmic radiation (GCR) component of space radiation is the dominant cause of single-event phenomena in microelectronic circuits when Earth's magnetic shielding is low. Spaceflights outside the magnetosphere and in high inclination orbits are examples of such circumstances. In high-inclination orbits, low-energy (high LET) particles are transmitted through the field only at extreme latitudes, but can dominate the orbit-averaged dose. GCR is an important part of the radiation dose to astronauts under the same conditions. As a test of the CREME environmental model and particle transport codes used to estimate single event upsets, we have compiled existing measurements of HZE doses were compiled where GCR is expected to be important: Apollo 16 and 17, Skylab, Apollo Soyuz Test Project, and Kosmos 782. The LET spectra, due to direct ionization from GCR, for each of these missions has been estimated. The resulting comparisons with data validate the CREME model predictions of high-LET galactic cosmic-ray fluxes to within a factor of two. Some systematic differences between the model and data are identified.

Dosimetric applications of cellular electrophysiological changes under high- and low-LET irradiation in health physics

International Nuclear Information System (INIS)

Steinhausler, F.; Hofmann, W.; Eckl, P.; Pohl-Ruling, J.

1980-01-01

The first step of interaction of radiation with any biological target occurs at the cellular level, especially at the cell membrane. This results in a Linear Energy Transfer (LET)-dependent deposition of energy at membrane substructures, where the supramolecular arrangement of components represents highly sensitive targets for ionizing radiation, e.g. the natural membrane lipid component. As part of a current research project on the influence of low level effects of ionizing radiation on biophysical cellular parameters, changes of electrical properties of irradiated cell membranes were studied for their suitability as biological dosimeters. Normal human embryonic lung cells (Flow 2002) and transformed human lung cells (WI-38/SV13) were exposed to ionizing radiation with LET ranging from 10 to over 100 keV/μm. With the use of micromanipulators, glass-micro-electrodes in a special headstage were used to determine intracellular electrical activity at different time intervals after irradiation of the cells. Population density of the irradiated cell colonies was varied in order to determine the influence of contact inhibition and intercellular communication on the observable radiation induced effect. Dose- and dose rate-dependent variation of cellular membrane resting potential and membrane resistance are discussed for both normal and malignant human cells. (author)

Methods of assessing total doses integrated across pathways

International Nuclear Information System (INIS)

Grzechnik, M.; Camplin, W.; Clyne, F.; Allott, R.; Webbe-Wood, D.

2006-01-01

Calculated doses for comparison with limits resulting from discharges into the environment should be summed across all relevant pathways and food groups to ensure adequate protection. Current methodology for assessments used in the radioactivity in Food and the Environment (R.I.F.E.) reports separate doses from pathways related to liquid discharges of radioactivity to the environment from those due to gaseous releases. Surveys of local inhabitant food consumption and occupancy rates are conducted in the vicinity of nuclear sites. Information has been recorded in an integrated way, such that the data for each individual is recorded for all pathways of interest. These can include consumption of foods, such as fish, crustaceans, molluscs, fruit and vegetables, milk and meats. Occupancy times over beach sediments and time spent in close proximity to the site is also recorded for inclusion of external and inhalation radiation dose pathways. The integrated habits survey data may be combined with monitored environmental radionuclide concentrations to calculate total dose. The criteria for successful adoption of a method for this calculation were: Reproducibility can others easily use the approach and reassess doses? Rigour and realism how good is the match with reality?Transparency a measure of the ease with which others can understand how the calculations are performed and what they mean. Homogeneity is the group receiving the dose relatively homogeneous with respect to age, diet and those aspects that affect the dose received? Five methods of total dose calculation were compared and ranked according to their suitability. Each method was labelled (A to E) and given a short, relevant name for identification. The methods are described below; A) Individual doses to individuals are calculated and critical group selection is dependent on dose received. B) Individual Plus As in A, but consumption and occupancy rates for high dose is used to derive rates for application in

Calculated LET spectrum from antiproton beams stopping in water

CERN Document Server

Bassler, Niels

2009-01-01

Antiprotons have been proposed as a potential modality for radiotherapy because the annihilation at the end of range leads to roughly a doubling of physical dose in the Bragg peak region. So far it has been anticipated that the radiobiology of antiproton beams is similar to that of protons in the entry region of the beam, but very different in the annihilation region, due to the expected high-LET components resulting from the annihilation. On closer inspection we find that calculations of dose averaged LET in the entry region may suggest that the RBE of antiprotons in the plateau region could significantly differ from unity, which seems to warrant closer inspection of the radiobiology in this region. Materials and Methods. Monte Carlo simulations using FLUKA were performed for calculating the entire particle spectrum of a beam of 126 MeV antiprotons hitting a water phantom. Results and Discussion. In the plateau region of the simulated antiproton beam we observe a dose-averaged unrestrict...

Internal high linear energy transfer (LET) targeted radiotherapy for cancer

International Nuclear Information System (INIS)

Allen, Barry J

2006-01-01

High linear energy transfer (LET) radiation for internal targeted therapy has been a long time coming on to the medical therapy scene. While fundamental principles were established many decades ago, the clinical implementation has been slow. Localized neutron capture therapy, and more recently systemic targeted alpha therapy, are at the clinical trial stage. What are the attributes of these therapies that have led a band of scientists and clinicians to dedicate so much of their careers? High LET means high energy density, causing double strand breaks in DNA, and short-range radiation, sparing adjacent normal tissues. This targeted approach complements conventional radiotherapy and chemotherapy. Such therapies fail on several fronts. Foremost is the complete lack of progress for the control of primary GBM, the holy grail for cancer therapies. Next is the inability to regress metastatic cancer on a systemic basis. This has been the task of chemotherapy, but palliation is the major application. Finally, there is the inability to inhibit the development of lethal metastatic cancer after successful treatment of the primary cancer. This review charts, from an Australian perspective, the developing role of local and systemic high LET, internal radiation therapy. (review)

Mutagenic action of radiation with different LET on Bacillus subtilis cells

International Nuclear Information System (INIS)

edinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" data-affiliation=" (Obedinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" >Borejko, A.V.; edinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" data-affiliation=" (Obedinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" >Krasavin, E.A.

1997-01-01

The induction of the his - -> his + mutants in vegetative and spores of Bacillus subtilis wild type cells irradiated with γ-rays and helium ions (LET = 20-80 keV/μm) has been investigated. It was shown that the dose dependence of the mutation induction in vegetative cells is described by a linear-quadratic function of dose in case of both γ-rays and helium ions. RBE (LET) dependencies on the lethal and mutagenic effect of radiation have a local maximum. The maximum of RBE (LET) dependence on the mutagenic assay is shifted at the low region of LET in comparison with the lethal effect of irradiation. (author)

Secondary radiation dose during high-energy total body irradiation

Energy Technology Data Exchange (ETDEWEB)

Janiszewska, M.; Raczkowski, M. [Lower Silesian Oncology Center, Medical Physics Department, Wroclaw (Poland); Polaczek-Grelik, K. [University of Silesia, Medical Physics Department, Katowice (Poland); Szafron, B.; Konefal, A.; Zipper, W. [University of Silesia, Department of Nuclear Physics and Its Applications, Katowice (Poland)

2014-05-15

The goal of this work was to assess the additional dose from secondary neutrons and γ-rays generated during total body irradiation (TBI) using a medical linac X-ray beam. Nuclear reactions that occur in the accelerator construction during emission of high-energy beams in teleradiotherapy are the source of secondary radiation. Induced activity is dependent on the half-lives of the generated radionuclides, whereas neutron flux accompanies the treatment process only. The TBI procedure using a 18 MV beam (Clinac 2100) was considered. Lateral and anterior-posterior/posterior-anterior fractions were investigated during delivery of 2 Gy of therapeutic dose. Neutron and photon flux densities were measured using neutron activation analysis (NAA) and semiconductor spectrometry. The secondary dose was estimated applying the fluence-to-dose conversion coefficients. The main contribution to the secondary dose is associated with fast neutrons. The main sources of γ-radiation are the following: {sup 56}Mn in the stainless steel and {sup 187}W of the collimation system as well as positron emitters, activated via (n,γ) and (γ,n) processes, respectively. In addition to 12 Gy of therapeutic dose, the patient could receive 57.43 mSv in the studied conditions, including 4.63 μSv from activated radionuclides. Neutron dose is mainly influenced by the time of beam emission. However, it is moderated by long source-surface distances (SSD) and application of plexiglass plates covering the patient body during treatment. Secondary radiation gives the whole body a dose, which should be taken into consideration especially when one fraction of irradiation does not cover the whole body at once. (orig.) [German] Die zusaetzliche Dosis durch sekundaere Neutronen- und γ-Strahlung waehrend der Ganzkoerperbestrahlung mit Roentgenstrahlung aus medizinischen Linearbeschleunigern wurde abgeschaetzt. Bei der Emission hochenergetischer Strahlen zur Teletherapie finden hauptsaechlich im Beschleuniger

High LET radiation enhances apoptosis in mutated p53 cancer cells through Caspase-9 activation

International Nuclear Information System (INIS)

Yamakawa, Nobuhiro; Takahashi, Akihisa; Mori, Eiichiro; Imai, Yuichiro; Ohnishi, Ken; Kirita, Tadaaki; Ohnishi, Takeo; Furusawa, Yoshiya

2008-01-01

Although mutations in the p53 gene can lead to resistance to radiotherapy, chemotherapy and thermotherapy, high linear energy transfer (LET) radiation induces apoptosis regardless of p53 gene status in cancer cells. The aim of this study was to clarify the mechanisms involved in high LET radiation-induced apoptosis. Human gingival cancer cells (Ca9-22 cells) containing a mutated p53 (mp53) gene were irradiated with X-rays, C-ion (13-100 KeV/μm), or Fe-ion beams (200 KeV/μm). Cellular sensitivities were determined using colony forming assays. Apoptosis was detected and quantified with Hoechst 33342 staining. The activity of Caspase-3 was analyzed with Western blotting and flow cytometry. Cells irradiated with high LET radiation showed a high sensitivity with a high frequency of apoptosis induction. The relative biological effectiveness (RBE) values for the surviving fraction and apoptosis induction increased in a LET-dependent manner. Both RBE curves reached a peak at 100 KeV/μm, and then decreased at values over 100 KeV/μm. When cells were irradiated with high LET radiation, Caspase-3 was cleaved and activated, leading to poly (ADP-ribose) polymerase (PARP) cleavage. In addition, Caspase-9 inhibitor suppressed Caspase-3 activation and apoptosis induction resulting from high LET radiation to a greater extent than Caspase-8 inhibitor. These results suggest that high LET radiation enhances apoptosis by activation of Caspase-3 through Caspase-9, even in the presence of mp53. (author)

Application of a Pelletron accelerator to study total dose radiation effects on 50 GHz SiGe HBTs

Energy Technology Data Exchange (ETDEWEB)

Praveen, K.C.; Pushpa, N.; Naik, P.S. [Department of Studies in Physics, University of Mysore, Manasagangotri, Mysore 570 006 (India); Cressler, John D. [School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA (United States); Tripathi, Ambuj [Inter University Accelerator Centre (IUAC), New Delhi 110 067 (India); Gnana Prakash, A.P., E-mail: gnanaprakash@physics.uni-mysore.ac.in [Department of Studies in Physics, University of Mysore, Manasagangotri, Mysore 570 006 (India)

2012-02-15

Highlights: Black-Right-Pointing-Pointer Total dose effects of 50 MeV Li3+ ion on 50 GHz SiGe HBTs is investigated. Black-Right-Pointing-Pointer Ion irradiated results were compared with Co-60 gamma results. Black-Right-Pointing-Pointer 50 MeV Li ions create more damage in E-B spacer oxide when compared to Co-60 gamma radiation. Black-Right-Pointing-Pointer Co-60 gamma radiation create more damage in STI oxide when compared to 50 MeV Li ions. Black-Right-Pointing-Pointer Worst case total dose radiation effects can be studied using Pelletron accelerator facilities. - Abstract: We have investigated the effects of 50 MeV lithium ion irradiation on the DC electrical characteristics of first-generation silicon-germanium heterojunction bipolar transistors (50 GHz SiGe HBTs) in the dose range of 600 krad to 100 Mrad. The results of 50 MeV Li{sup 3+} ion irradiation on the SiGe HBTs are compared with 63 MeV proton and Co-60 gamma irradiation results in the same dose range in order to understand the damage induced by different LET species. The radiation response of emitter-base (EB) spacer oxide and shallow trench isolation (STI) oxide to different irradiation types are discussed in this paper. We have also focused on the efficacy in the application of a Pelletron accelerator to study total dose irradiation studies in SiGe HBTs.

Mutagenic action of radiation with different LET on Bacillus subtilis cells

International Nuclear Information System (INIS)

Borejko, A.V.; Krasavin, E.A.

1996-01-01

The induction of the his - →his + mutants in vegetative and spores of Bacillus subtilis wild type cells irradiated with γ-rays and helium ions (LET=20-80 keV/μm has been investigated. It was shown that the dose dependence of the mutation induction in vegetative cells is described by a linear-quadratic function of dose in case of both γ-rays and helium ions. RBE (LET) dependence on the mutagenic assay is shifted at the low region of LET. (author). 11 refs., 4 figs

The Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage: Track Structure Effects and Cytogenetic Signatures of High-LET Exposure

Science.gov (United States)

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

2012-01-01

Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to 195 keV/micrometers. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons. All energies of protons have a much higher percentage of complex-type chromosome exchanges than gamma rays, signifying a cytogenetic signature for proton exposures.

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

International Nuclear Information System (INIS)

Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

1981-01-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors

High LET Radiation Amplifies Centrosome Overduplication Through a Pathway of γ-Tubulin Monoubiquitination

Energy Technology Data Exchange (ETDEWEB)

Shimada, Mikio [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto (Japan); Hirayama, Ryoichi [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Komatsu, Kenshi, E-mail: komatsu@house.rbc.kyoto-u.ac.jp [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto (Japan)

2013-06-01

Purpose: Radiation induces centrosome overduplication, leading to mitotic catastrophe and tumorigenesis. Because mitotic catastrophe is one of the major tumor cell killing factors in high linear energy transfer (LET) radiation therapy and long-term survivors from such treatment have a potential risk of secondary tumors, we investigated LET dependence of radiation-induced centrosome overduplication and the underlying mechanism. Methods and Materials: Carbon and iron ion beams (13-200 keV/μm) and γ-rays (0.5 keV/μm) were used as radiation sources. To count centrosomes after IR exposure, human U2OS and mouse NIH3T3 cells were immunostained with antibodies of γ-tubulin and centrin 2. Similarly, Nbs1-, Brca1-, Ku70-, and DNA-PKcs-deficient mouse cells and their counterpart wild-type cells were used for measurement of centrosome overduplication. Results: The number of excess centrosome-containing cells at interphase and the resulting multipolar spindle at mitosis were amplified with increased LET, reaching a maximum level of 100 keV/μm, followed by sharp decrease in frequency. Interestingly, Ku70 and DNA-PKcs deficiencies marginally affected the induction of centrosome overduplication, whereas the cell killings were significantly enhanced. This was in contrast to observation that high LET radiation significantly enhanced frequencies of centrosome overduplication in Nbs1- and Brca1-deficient cells. Because NBS1/BRCA1 is implicated in monoubiquitination of γ-tubulin, we subsequently tested whether it is affected by high LET radiation. As a result, monoubiquitination of γ-tubulin was abolished in 48 to 72 hours after exposure to high LET radiation, although γ-ray exposure slightly decreased it 48 hours postirradiation and was restored to a normal level at 72 hours. Conclusions: High LET radiation significantly reduces NBS1/BRCA1-mediated monoubiquitination of γ-tubulin and amplifies centrosome overduplication with a peak at 100 keV/μm. In contrast, Ku70 and DNA

Dose rate and dose fractionation studies in total body irradiation of dogs

International Nuclear Information System (INIS)

Kolb, H.J.; Netzel, B.; Schaffer, E.; Kolb, H.

1979-01-01

Total body irradiation (TBI) with 800-900 rads and allogeneic bone marrow transplantation according to the regimen designated by the Seattle group has induced remissions in patients with otherwise refractory acute leukemias. Relapse of leukemia after bone marrow transplantation remains the major problem, when the Seattle set up of two opposing 60 Co-sources and a low dose rate is used in TBI. Studies in dogs with TBI at various dose rates confirmed observations in mice that gastrointestinal toxicity is unlike toxicity against hemopoietic stem cells and possibly also leukemic stem cells depending on the dose rate. However, following very high single doses (2400 R) and marrow infusion acute gastrointestinal toxicity was not prevented by the lowest dose rate studied (0.5 R/min). Fractionated TBI with fractions of 600 R in addition to 1200 R (1000 rads) permitted the application of total doses up to 300 R followed by marrow infusion without irreversible toxicity. 26 dogs given 2400-3000 R have been observed for presently up to 2 years with regard to delayed radiation toxicity. This toxicity was mild in dogs given single doses at a low dose rate or fractionated TBI. Fractionated TBI is presently evaluated with allogeneic transplants in the dog before being applied to leukemic patients

Injury to the central nervous system after high LET radiation

International Nuclear Information System (INIS)

Laramore, G.E.

1991-01-01

To date, clinical experiments with high LET irradiation have used fast neutrons, π-mesons, and heavy ions. The data for all of these modalities will be reviewed here, but by far the greatest body of information is for fast neutrons. Boron neutron capture therapy work for brain tumors, and interesting area in its own right, will not be discussed. In the paper, the author considered separately the brain and the spinal cord in terms of radiation effects. Most of the information on the brain comes from the treatment of high-grade gliomas and so the effects of the tumor and its surrounding edema must be folded in. There is, however, some information relating to the treatment of tumors lying adjacent to the brain. The spinal cord data come primarily from the treatment of head and neck tumors and intrathoracic tumors. Because the majority of these tumors were quite advanced, they often caused the patient's early death, and many patients may not have survived long enough to show the effects of radiation damage even if doses were given that exceeded cord tolerance

Cosmic radiation dose in the aircraft

International Nuclear Information System (INIS)

Vukovic, B.; Radolic, V.; Varga, M.; Planinic, J.; Vekic, B.

2006-01-01

When primary particles from space, mainly protons, enter the atmosphere, they produce interactions with air nuclei, and cosmic-ray showers are induced. The radiation field at aircraft altitude is complex, with different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard A 320 and ATR 42 aircraft was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter; the neutron dose was measured with the neutron dosimeter consisted of LR-115 track detector and boron foil BN-1 or 10B converter. The estimated occupational effective dose for the aircraft crew (A320) working 500 h per year was 1.64 mSv. Another experiment was performed at the flights Zagreb - Paris - Buenos Aires and reversely, when one measured cosmic radiation dose; for 26.7 h of flight, the MINI 6100 dosimeter gave an average dose rate of 2.3 μSv/h and the TLD dosimeter registered the total dose of 75 μSv or the average dose rate of 2.7 μSv/h; the neutron dosimeter gave the dose rate of 2.4 μSv/h. In the same month, February 2005, a traveling to the Japan (24 hours-flight: Zagreb - Frankfurt - Tokyo and reversely) and the TLD-100 measurement showed the average dose rate of 2.4 μSv/h; the neutron dosimeter gave the dose rate of 2.5 μSv/h. Comparing dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level, we could conclude the neutron component curried about 50% of the total dose, that was near other known data. (author)

Risk assessment for cancer induction after low- and high-LET therapeutic irradiation

International Nuclear Information System (INIS)

Engels, H.; Menzel, H.G.; Pihet, P.; Wambersie, A.

1999-01-01

The risk of induction of a second primary cancer after a therapeutic irradiation with conventional photon beams is well recognized and documented. However, in general, it is totally overwhelmed by the benefit of the treatment. The same is true to a large extent for the combinations of radiation and drug therapy. After fast neutron therapy, the risk of induction of a second cancer is greater than after photon therapy. Neutron RBE increases with decreasing dose and there is a wide evidence that neutron RBE is greater for cancer induction (and for other late effects relevant in radiation protection) than for cell killing. Animal data on RBE for tumor induction are reviewed, as well as other biological effects such as life shortening, malignant cell transformation in vitro, chromosome aberrations, genetic effects. These effects can be related, directly or indirectly, to cancer induction to the extent that they express a 'genomic' lesions. Almost no reliable human epidemiological data are available so far. For fission neutrons a RBE for cancer induction of about 20 relative to photons seems to be a reasonable assumption. For fast neutrons, due to the difference in energy spectrum, a RBE of 10 can be assumed. After proton beam therapy (low-LET radiation), the risk of secondary cancer induction, relative to photons, can be divided by a factor of 3, due to the reduction of integral dose (as an average). The RBE of heavy-ions for cancer induction can be assumed to be similar to fission neutrons, i.e. about 20 relative to photons. However, after heavy-ion beam therapy, the risk should be divided by 3, as after proton therapy, due to the excellent physical selectivity of the irradiation. Therefore, a risk 5 to 10 times higher than photons could be assumed. This range is probably a pessimistic estimate for carbon ions since most of the normal tissues, at the level of the initial plateau, are irradiated with low-LET radiation. (orig.)

High Total Ionizing Dose and Temperature Effects on Micro- and Nano-electronic Devices

International Nuclear Information System (INIS)

Gaillardin, M.; Martinez, M.; Paillet, P.; Leray, J.L.; Marcandella, C.; Duhamel, O.; Raine, M.; Richard, N.; Girard, S.; Ouerdane, Y.; Boukenter, A.; Goiffon, V.; Magnan, P.; Andrieu, F.; Barraud, S.; Faynot, O.

2013-06-01

This paper investigates the vulnerability of several micro- and nano-electronic technologies to a mixed harsh environment including high total ionizing dose at MGy levels and high temperature. Such operating conditions have been revealed recently for several applications like new security systems in existing or future nuclear power plants, fusion experiments, or deep space missions. In this work, the competing effects already reported in literature of ionizing radiations and temperature are characterized in elementary devices made of MOS transistors from several technologies. First, devices are irradiated using a radiation laboratory X-ray source up to MGy dose levels at room temperature. Devices are grounded during irradiation to simulate a circuit which waits for a wake up signal, representing most of the lifetime of an integrated circuit operating in a harsh environment. Devices are then annealed at several temperatures to discuss the post-irradiation behavior and to determine whether an elevated temperature is an issue or not for circuit function in mixed harsh environments. (authors)

Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

Science.gov (United States)

Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for γ-radiation. When total doses of 96 or 247 cGy of neutrons or γ rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and γ-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or γ rays, a significant age- and radiation-related deficiency

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

Science.gov (United States)

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.

Experimental and calculated LET distributions in the Cosmos-2044 biosatellite orbit

International Nuclear Information System (INIS)

Dudkin, V.E.; Karpov, O.N.; Potapov, Yu.V.; Benton, E.V.; Frank, A.L.; Watts, J.W. Jr.

1992-01-01

During the flight of the Cosmos-2044 biosatellite, joint U.S.S.R.-U.S.A. investigations of different characteristics of cosmic radiation (CR) in the near-Earth environment were carried out. The U.S. dielectric track detectors CR-39 and Soviet BYa- and BR-type nuclear photo-emulsions were used as detectors. The present work shows some results of experimental measurements of linear energy transfer (LET) spectra of CR particles obtained with the use of these detectors, which were placed both inside and outside the satellite. The LET spectra measurement with plastic detectors is composed of two parts: the measurement of galactic cosmic rays (GCR) particles, and of short-range particles. The contributions of these components to the total LET distribution at various thicknesses of the shielding were analyzed and the results of these studies are presented. Calculated LET spectra in the Cosmos-2044 orbit were compared with experimental data. On the basis of experimental and calculated values of the LET spectra, absorbed and equivalent CR doses were calculated. In the shielding range of 1-1.5 g cm -2 , outside the spacecraft, the photo-emulsions yielded 10.3 mrad d -1 and 27.5 mrem d -1 (LET ≥ 2 MeV cm -1 ) while the CR-39 yielded averages of 1.43 mrad d -1 and 13.4 mrem d -1 (LET ≥ 40 MeV cm -1 ). Inside the spacecraft (≥10 g cm -2 ) the photo-emulsions yielded 8.9 mrad d -1 and 14.5 mrem d -1 . (author)

In vitro cellular transformation induced by charged particles of defined LET

International Nuclear Information System (INIS)

Hei, T.K.; Hall, E.J.; Komatsu, K.; Goldhagen, P.

1985-01-01

Cytotoxicity and neoplastic transformation were scored in the C/sub 3/H 10T1/2 cell system following irradiation with protons, deuterons and helium-3 ions of defined LET in the track segment mode. The charged particles were accelerated at the Radiological Research Accelerator Facility at the Nevis Laboratories of Columbia University and provided a range of LET values from 10 to 175 keV/μm. Exponential phase cultures of C3H 10T1/2 cells, growing on a thin mylar surface were irradiated with charged particles of various LET values and subsequently replated onto commercial plastic petri dishes. The cultures were incubated for six weeks at which time they were fixed, stained and type II and III scored as transformants. Over the range of LET values studied thus far, it was found that as the LET of the charged particles increased, the shoulder of the survival curves decreased and approached an exponential function of dose at LET values of 100 keV/μm and above. The transformation incidence, likewise, showed a direct correlation with LET over the dose ranges examined

Total dose effects on ATLAS-SCT front-end electronics

CERN Document Server

Ullán, M; Dubbs, T; Grillo, A A; Spencer, E; Seiden, A; Spieler, H; Gilchriese, M G D; Lozano, M

2002-01-01

Low dose rate effects (LDRE) in bipolar technologies complicate the hardness assurance testing for high energy physics applications. The damage produced in the ICs in the real experiment can be underestimated if fast irradiations are carried out, while experiments done at the real dose rate are usually unpractical due to the still high total doses involved. In this work the sensitivity to LDRE of two bipolar technologies proposed for the ATLAS-SCT experiment at CERN is evaluated, finding one of them free of those effects. (12 refs).

Cytotoxic and mutagenic effects of high let charged particles on human skin fibroblasts

International Nuclear Information System (INIS)

Tsuboi, Koji.; Park, M.S.; Chen, D.J.; Yang, T.C.

1992-01-01

Cytotoxic and mutagenic effects of high LET charged particles were quantitatively measured using primary cultures of human skin fibroblasts. The span of LETs selected were from 25 keV/μm(330 MeV/u) to 920 keV/μm (600 MeV/u). Mutations were scored at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus using 6-thioguanine (6-TG) for selection. Exposure to these high LET charged particles resulted in exponential survival curves whereas mutant induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/μm. The inactivation cross-section (σ i ) and the action cross-section for mutant induction (σ m ) ranged from 2.2 to 92.0 μm 2 and 0.09 to 5.56 x 10 -3 μm 2 respectively, the maximum values were obtained by 56 Fe with an LET of 200 keV/μm. The mutagenicity (σ m /σ i ) ranged from 2.05 to 7.99 x 10 -5 with the maximum value at 150 keV/μm. Furthermore, the results of multiplex polymerase chain reaction (PCR) of some of the mutants induced by charged particles indicate that higher LET beams are more likely to cause larger deletions in the hprt locus. (author)

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

Energy Technology Data Exchange (ETDEWEB)

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

WE-E-BRE-07: High-Throughput Mapping of Proton Biologic Effect

Energy Technology Data Exchange (ETDEWEB)

Bronk, L; Guan, F; Kerr, M; Dinh, J; Titt, U; Mirkovic, D; Lin, S; Mohan, R; Grosshans, D [UT MD Anderson Cancer Center, Houston, TX (United States)

2014-06-15

Purpose: To systematically relate the relative biological effectives (RBE) of proton therapy to beam linear energy transfer (LET) and dose. Methods: Using a custom irradiation apparatus previously characterized by our group, H460 NSCLCs were irradiated using a clinical 80MeV spot scanning proton beam. Utilizing this system allowed for high-throughput clonogenic assays performed in 96-well tissue culture plates as opposed to the traditional 6-well technique. Each column in the 96-well plate received a set LET-dose combination. By altering the total number of dose repaintings, numerous dose-LET configurations were examined to effectively generate surviving fraction (SF) data over the entire Bragg peak. The clonogenic assay was performed post-irradiation using an INCell Analyzer for colony quantification. SF data were fit to the linear-quadratic model for analysis. Results: Irradiation with increasing LETs resulted in decreased cell survival largely independent of dose. A significant correlation between LET and SF was identified by two-way ANOVA and the extra sum-of-squares F test. This trend was obscured at the lower LET values in the plateau region of the Bragg peak; however, it was clear for LET values at and beyond the Bragg peak. Data fits revealed the SF at a dose of 2Gy (SF2) to be 0.48 for the lowest tested LET (1.55keV/um), 0.47 at the end of the plateau region (4.74keV/um) and 0.33 for protons at the Bragg peak (10.35keV/um). Beyond the Bragg peak we measured SF2s of 0.16 for 15.01keV/um, 0.02 for 16.79keV/um, and 0.004 for 18.06keV/um. Conclusion: We have shown that our methodology enables high-content automated screening for proton irradiations over a range of LETs. The observed decrease in cellular SF in high LET regions confirms an increased RBE of the radiation and suggests further evaluation of proton RBE values is necessary to optimize clinical outcomes. Rosalie B. Hite Graduate Fellowship in Cancer Research, NIH Program Project Grant P01CA021239.

Design criteria for a hemispherical detector for LET measurements

International Nuclear Information System (INIS)

Schell, M.C.; DeLuca, P.M. Jr.; Pearson, D.W.; Attix, F.H.

1980-01-01

A detector for the direct measurement of the Linear Energy Transfer (LET) in cylindrical geometry was developed by Brandan and DeLuca. The detector successfully measured the LET of protons and a fraction of the heavy charged particles generated in cylindrical A150 plastic and graphite walls by 14.8 MeV neutrons. In this report, we present design tests for the hemispherical LET detector which will measure the LET of charged particles in spherical geometry and allow comparison with calculated LET spectra. The hemispherical LET detector will also provide a data base for radiobiological predictions with the Track Structure Model by Katz. A comparison of predictions of radiobiological effects by the Theory of Dual Radiation Action and the Track Structure Model by Edwards and the authors indicate that the Track Structure Model predicts cell survival as a function of dose more accurately and hence an additional motivation for the present construction of the hemispherical LET detector

Combined chemo/radiotherapy of cancer: present state and prospects for use with high-LET radiotherapy

International Nuclear Information System (INIS)

Phillips, T.L.

1979-01-01

Cytotoxic chemotherapy added to low-LET radiotherapy has improved survival and in some cases local control. In some instances the combination has yielded increased normal tissue damage. Similar results can be expected, as confirmed by intestinal crypt cell experiments, with high-LET. Less interaction than with low-LET appears to occur with agents blocking sublethal damage repair or causing synchronization. (author)

Generalized concept of the LET-RBE relationship of radiation-induced chromosome aberration and cell death

International Nuclear Information System (INIS)

Takatsuji, Toshihiro; Yoshikawa, Isao; Sasaki, Masao S.

1999-01-01

The frequency of chromosome aberrations per traversal of a nucleus by a charged particle at the low dose limit increases proportionally to the square of the linear energy transfer (LET), peaks at about 100 keV/μm and then decreases with further increase of LET. This has long been interpreted as an excessive energy deposition over the necessary energy required to produce a biologically effective event. Here, we present an alternative interpretation. Cell traversed by a charged particle has certain probability to receive lethal damage leading to direct death. Such events may increase with an increase of LET and the number of charged particles traversing the cell. Assuming that the lethal damage is distributed according to a Poisson distribution, the probability that a cell has no such damage is expressed by e -cLx , where c is a constant, L is LET, and x is the number of charged particles traversing the cell. From these assumptions, the frequency of chromosome aberration in surviving cells can be described by Y=αSD+βS 2 D 2 with the empirical relation Y=αD+βD 2 in the low LET region, where S=e -cL , α is a value proportional to LET, β is a constant, and D is the absorbed dose. This model readily explains the empirically established relationship between LET and relative biological effectiveness (RBE). The model can also be applied to clonogenic survival. If cells can survive and they have neither unstable chromosome aberrations nor other lethal damage, the LET-RBE relationship for clonogenic survival forms a humped curve. The relationship between LET and inactivation cross-section becomes proportional to the square of LET in the low LET region when the frequency of a directly lethal events is sufficiently smaller than unity, and the inactivation cross-section saturates to the cell nucleus cross-sectional area with an increase in LET in the high LET region. (author)

Evaluation of normal tissue responses to high-LET radiations

International Nuclear Information System (INIS)

Halnan, K.E.

1979-01-01

Clinical results presented have been analysed to evaluate normal tissue responses to high-LET radiations. Damage to brain, spinal cord, gut, skin, connective tissue and bone has occurred. A high RBE is probable for brain and possible for spinal cord and gut but other reasons for damage are also discussed. A net gain seems likely. Random controlled trials are advocated. (author)

The dependence of relative biological effectiveness from LET

International Nuclear Information System (INIS)

Savich, A.V.

1985-01-01

A dependence of radiation-chemical yields of DNA injuries on the LET value is found for two transformations - one and two-strand breaks of it. It is shown that the yield of one-strand breaks decreases with the increase of LET value, and the quantity of two-strand breaks at first increases reaching the maximum value within the LET range from 100 up to 150 eV/nm and then decreases. The considered semiempiric theories of the RBE dependences on LET permits using the experimentally determined parameters characterizing radiosensitivity, to estimate the efficiency of the effect of ionizing radiation on cells at different doses, types of radiation and levels of saturation with oxygen. The stage of the cell cycle is also taken into account

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

Energy Technology Data Exchange (ETDEWEB)

Neubeck, Claere von [German Cancer Consortium DKTK partner site Dresden, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden (Germany); German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Geniza, Matthew J. [Molecular and Cellular Biology Program, Oregon State University, Corvallis OR 97331 (United States); Kauer, Paula M.; Robinson, R. Joe; Chrisler, William B. [Health Impacts and Exposure Science, Pacific Northwest National Laboratory, Richland WA 99352 (United States); Sowa, Marianne B., E-mail: marianne.sowa@pnnl.gov [Health Impacts and Exposure Science, Pacific Northwest National Laboratory, Richland WA 99352 (United States)

2015-05-15

Highlights: • Low doses of high LET radiation influence skin homeostasis. • Effects on proliferation and differentiation profiles are LET dependent. • Skin barrier function is not compromised following low dose exposure. - Abstract: 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.

VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation

International Nuclear Information System (INIS)

Fujisawa, Hiroshi; Nakajima, Nakako Izumi; Sunada, Shigeaki; Lee, Younghyun; Hirakawa, Hirokazu; Yajima, Hirohiko; Fujimori, Akira; Uesaka, Mitsuru; Okayasu, Ryuichi

2015-01-01

High linear energy transfer (LET) radiation such as carbon ion particles is successfully used for treatment of solid tumors. The reason why high LET radiation accomplishes greater tumor-killing than X-rays is still not completely understood. One factor would be the clustered or complex-type DNA damages. We previously reported that complex DNA double-strand breaks produced by high LET radiation enhanced DNA end resection, and this could lead to higher kinase activity of ATR protein recruited to RPA-coated single-stranded DNA. Although the effect of ATR inhibition on cells exposed to low LET gamma-rays has recently been reported, little is known regarding the effect of ATR inhibitor on cells treated with high LET radiation. The purpose of this study is to investigate the effects of the ATR inhibitor VE-821 in human tumor and normal cells irradiated with high LET carbon ions. HeLa, U2OS, and 1BR-hTERT (normal) cells were pre-treated with 1 μM VE-821 for 1 hour and irradiated with either high LET carbon ions or X-rays. Cell survival, cell cycle distribution, cell growth, and micronuclei formation were evaluated. VE-821 caused abrogation of G2/M checkpoint and forced irradiated cells to divide into daughter cells. We also found that carbon ions caused a higher number of multiple micronuclei than X-rays, leading to decreased cell survival in tumor cells when treated with VE-821, while the survival of irradiated normal cells were not significantly affected by this inhibitor. ATR inhibitor would be an effective tumor radiosensitizer with carbon ion irradiation. The online version of this article (doi:10.1186/s13014-015-0464-y) contains supplementary material, which is available to authorized users

LET-effects in DNA

International Nuclear Information System (INIS)

Kraft, G.; Taucher-Scholz, G.; Heilmann, J.

1995-01-01

The use of heavy particles in radiobiological experiments provides a fundamental tool to study the influence of different ionization densities and to prove the physical basis of models and theories. The knowledge of the interaction of high LET radiation (LET: linear energy transfer [keV/microm]) with biological matter is of great importance for the application of neutrons, protons and heavier ions in radiotherapy. It is also essential in radioprotection to estimate the risk in case of exposure to high LET radiation. In this contribution, an introductory view on the physical properties of ions is given and the cellular response to high LET radiation is summarized. Then the measurements of strand break induction of DNA in solution and in intracellular DNA are reported and compared to cell survival. The possibility of changes in the quality of the lesions is discussed and finally the present status of model calculations in comparison to the experiments is given

Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness

Science.gov (United States)

Schmid, T. E.; Greubel, C.; Hable, V.; Zlobinskaya, O.; Michalski, D.; Girst, S.; Siebenwirth, C.; Schmid, E.; Molls, M.; Multhoff, G.; Dollinger, G.

2012-10-01

This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm-1) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBEMN = 1.48 ± 0.07) and dicentrics (RBED = 1.92 ± 0.15), in human-hamster hybrid (AL) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm2 matrix compared to quasi homogeneous in a 1 × 1 µm2 matrix applied protons (RBEMN = 1.28 ± 0.07; RBED = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a 12C ion with 55 MeV total energy (4.48 MeV u-1). The enhancements are about half of that obtained for 12C ions (RBEMN = 2.20 ± 0.06 and RBED = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles.

High-LET particle dosimetry in the ASTP-Biostack III: Zea mays experiment

International Nuclear Information System (INIS)

Peterson, D.D.; Benton, E.V.; Tran, M.; Yang, T.; Freeling, M.; Craise, L.; Tobias, C.A.

1977-01-01

High-LET particle hits in embryos of Zea mays (corn) seeds, flown as part of the ASTP-Biostack III, were determined via plastic nuclear track detectors. Based on etched particle-tracks measurements, 41 embryos were hit in seed layer 1 which contained 80 seeds, and 49 hits occurred in layer 2 which contained 79 seeds. The mean LET value and range of atomic numbers of recorded hits is, respectively, 210 +- 57 keV/μm and 9 approximately less than Z approximately less than 26. Detailed analysis of one particular seed showing marked growth anomalies revealed two hits in the central region of the embryo. These two hits had LET values in the region of 100 to 150 keV/μm, and Z less than approximately 20. (author)

High energy ion irradiation effects on polymer materials. LET dependence of G value of scission of polymethylmethacrylate (PMMA)

Energy Technology Data Exchange (ETDEWEB)

Kudoh, H; Sasuga, T; Seguchi, T [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

1997-03-01

Linear energy transfer (LET) dependence on the probability of main chain scission of polymethylmethacrylate (PMMA) was investigated. The probability was obtained from decreases in molecular weight measured by the gel permeation chromatography (GPC), and LET was evaluated by TRIM code. The scission probability as a function of LET was almost constant in the low LET, and decreased in the high LET ion irradiation. The mechanism was interpreted from the model of spur-overlapping along an ion`s path. (author)

High LET Radiation Can Enhance TGF(Beta) Induced EMT and Cross-Talk with ATM Pathways

Science.gov (United States)

Wang, Minli; Hada, Megumi; Huff, Janice; Pluth, Janice M.; Anderson, Janniffer; ONeill, Peter; Cucinotta, Francis A.

2010-01-01

The TGF(Beta) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation in mammary epithelial cells. We investigated possible interactions between the TGF(Beta) and ATM pathways following simulated space radiation using hTERT immortalized human esophageal epithelial cells (EPC-hTERT), mink lung epithelial cells (Mv1lu), and several human fibroblast cell lines. TGF(Beta) is a key modulator of the Epithelial-Mesenchymal Transition (EMT), important in cancer progression and metastasis. The implication of EMT by radiation also has several lines of developing evidence, however is poorly understood. The identification of TGF(Beta) induced EMT can be shown in changes to morphology, related gene over expression or down regulation, which can be detected by RT-PCR, and immunostaining and western blotting. In this study, we have observed morphologic and molecular alternations consistent with EMT after Mv1lu cells were treated with TGF(Beta) High LET radiation enhanced TGF(Beta) mediated EMT with a dose as low as 0.1Gy. In order to consider the TGF(Beta) interaction with ATM we used a potent ATM inhibitor Ku55933 and investigated gene expression changes and Smad signaling kinetics. Ku559933 was observed to reverse TGF(Beta) induced EMT, while this was not observed in dual treated cells (radiation+TGF(Beta)). In EPC-hTERT cells, TGF(Beta) alone was not able to induce EMT after 3 days of application. A combined treatment with high LET, however, significantly caused the alteration of EMT markers. To study the function of p53 in the process of EMT, we knocked down P53 through RNA interference. Morphology changes associated with EMT were observed in epithelial cells with silenced p53. Our study indicates: high LET radiation can enhance TGF(Beta) induced EMT; while ATM is triggering the process of TGF(Beta)-induced EMT, p53 might be an essential repressor for EMT phenotypes.

Cosmic radiation dose in aircraft - a neutron track etch detector

Energy Technology Data Exchange (ETDEWEB)

Vukovic, B.; Radolic, V.; Miklavcic, I.; Poje, M.; Varga, M. [Department of Physics, University of Osijek, 31000 Osijek, P.O. Box 125, Gajev trg 6 (Croatia); Planinic, J. [Department of Physics, University of Osijek, 31000 Osijek, P.O. Box 125, Gajev trg 6 (Croatia)], E-mail: planinic@ffos.hr

2007-12-15

Cosmic radiation bombards us at high altitude by ionizing particles. The radiation environment is a complex mixture of charged particles of solar and galactic origin, as well as of secondary particles produced in interaction of the galactic cosmic particles with the nuclei of atmosphere of the Earth. The radiation field at aircraft altitude consists of different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard ATR 42 and A 320 aircrafts (flight level of 8 and 11 km, respectively) was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter. The estimated occupational effective dose for the aircraft crew (A 320) working 500 h per year was 1.64 mSv. Other experiments, or dose rate measurements with the neutron dosimeter, consisting of LR-115 track detector and boron foil BN-1 or 10B converter, were performed on five intercontinental flights. Comparison of the dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level showed that the neutron component carried about 50% of the total dose. The dose rate measurements on the flights from the Middle Europe to the South and Middle America, then to Korea and Japan, showed that the flights over or near the equator region carried less dose rate; this was in accordance with the known geomagnetic latitude effect.

Cosmic radiation dose in aircraft - a neutron track etch detector

International Nuclear Information System (INIS)

Vukovic, B.; Radolic, V.; Miklavcic, I.; Poje, M.; Varga, M.; Planinic, J.

2007-01-01

Cosmic radiation bombards us at high altitude by ionizing particles. The radiation environment is a complex mixture of charged particles of solar and galactic origin, as well as of secondary particles produced in interaction of the galactic cosmic particles with the nuclei of atmosphere of the Earth. The radiation field at aircraft altitude consists of different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard ATR 42 and A 320 aircrafts (flight level of 8 and 11 km, respectively) was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter. The estimated occupational effective dose for the aircraft crew (A 320) working 500 h per year was 1.64 mSv. Other experiments, or dose rate measurements with the neutron dosimeter, consisting of LR-115 track detector and boron foil BN-1 or 10B converter, were performed on five intercontinental flights. Comparison of the dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level showed that the neutron component carried about 50% of the total dose. The dose rate measurements on the flights from the Middle Europe to the South and Middle America, then to Korea and Japan, showed that the flights over or near the equator region carried less dose rate; this was in accordance with the known geomagnetic latitude effect

Problems Associated with the Use of the Radiochromic Dye Film as a Radiation Dose Meter

DEFF Research Database (Denmark)

Hansen, Johnny; Wille, Mads; Olsen, Kjeld J.

1984-01-01

of coloration. The dose response has been found to depend strongly on: the time span between irradiation and measurement; the irradiation temperature; and the dose rate at doses above 50 kGy for low-LET radiation. Irradiation in vacuum (right-pointing angle bracket1 Pa) and in air produced the same dose......A thorough investigation has been made of the problems involved in using a dye film dose meter for precision dosimetry at high doses, using both low- and high-LET radiation. The study includes: time course of coloration following irradiation at various dose levels; dose response after irradiation...

Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 10: Towards LET detection: A study on the effects of scintillator doping

Energy Technology Data Exchange (ETDEWEB)

Nusrat, Humza; Pang, Geordi; Ahmad, Syed; Keller, Brian; Sarfehnia, Arman [Ryerson University, Sunnybrook Health Sciences Centre (Canada)

2016-08-15

Purpose: In radiotherapy, the amount of radiation delivered is determined by optimizing the amount of absorbed dose to the tumor. Dose does not always correlate well with the actual biological effects of radiation. This work seeks to validate the LET-dependence of doped plastic scintillators for use in a radiation beam quality (LET) detector. Methods: The LET spectrum ([Φ]) can be resolved knowing the measured signals of uniquely LET-dependent detectors, [S], and the response of each LET-dependent detector to specific LETs ([R]), through the relation [Φ]=[S][R]{sup −1}. Plastic scintillator response is intrinsically LET dependent and can be varied via doping. Initial prototype consists of plastic scintillator and glass taper coupled to an optical fiber; components are housed in black acrylic, reducing effect of ambient light. In order to determine [R], the light response matrix, GEANT4.10.1 Monte Carlo (MC) was used. To validate MC, measurements were done using high energy electrons (9,12,15MeV) and orthovoltage x-rays (100,250kV); scintillator signal was normalized to dose measured simultaneously. Results: Stopping power was varied by changing particle type/energy; measurements indicated that as stopping power increased from 1.9 to 6.6MeV/cm, detector response increased by 263% (+/−29.2%) for 5%Pb-doped scintillator (155% in MC); 52% (+/−7.8%) increase observed when undoped scintillator was used (49% in MC). 5%Pb-doped discrepancy (100kV x-rays) is being investigated. Conclusions: This work validates that doping effects LET/energy response of scintillators; an effect that can be utilized for construction of an LET detector.

A preliminary study on action mechanisms of surviving expression in cell apoptosis induced by high-LET radiation

International Nuclear Information System (INIS)

Jin Xiaodong; Li Qiang; Gong Li; Wu Qingfeng; Li Ping; Dai Zhongying; Liu Xinguo; Tao Jiajun

2010-01-01

It has been proven that over-expression of surviving in cancerous cell lines is related to the radioresistance of cells to high-LET radiation in previous work. In this study, action mechanisms of surviving gene in apoptosis induced by high-LET radiation were investigated. We found that inhibiting surviving by siRNA had no notable influence on Bcl-2 and Bax expressions induced by carbon ions. Surviving depressed cell apoptosis through the inhibition of the activities of caspase-3 and -9 possibly in cell apoptosis induced by high-LET radiation. (authors)

Enrichment increases hippocampal neurogenesis independent of blood monocyte-derived microglia presence following high-dose total body irradiation.

Science.gov (United States)

Ruitenberg, Marc J; Wells, Julia; Bartlett, Perry F; Harvey, Alan R; Vukovic, Jana

2017-06-01

Birth of new neurons in the hippocampus persists in the brain of adult mammals and critically underpins optimal learning and memory. The process of adult neurogenesis is significantly reduced following brain irradiation and this correlates with impaired cognitive function. In this study, we aimed to compare the long-term effects of two environmental paradigms (i.e. enriched environment and exercise) on adult neurogenesis following high-dose (10Gy) total body irradiation. When housed in standard (sedentary) conditions, irradiated mice revealed a long-lasting (up to 4 months) deficit in neurogenesis in the granule cell layer of the dentate gyrus, the region that harbors the neurogenic niche. This depressive effect of total body irradiation on adult neurogenesis was partially alleviated by exposure to enriched environment but not voluntary exercise, where mice were single-housed with unlimited access to a running wheel. Exposure to voluntary exercise, but not enriched environment, did lead to significant increases in microglia density in the granule cell layer of the hippocampus; our study shows that these changes result from local microglia proliferation rather than recruitment and infiltration of circulating Cx 3 cr1 +/gfp blood monocytes that subsequently differentiate into microglia-like cells. In summary, latent neural precursor cells remain present in the neurogenic niche of the adult hippocampus up to 8 weeks following high-dose total body irradiation. Environmental enrichment can partially restore the adult neurogenic process in this part of the brain following high-dose irradiation, and this was found to be independent of blood monocyte-derived microglia presence. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Linear dose response curves in fungi and tradescantia

International Nuclear Information System (INIS)

Unrau, P.

1999-07-01

heterozygosity (LOH) events occur because Clone 02 repairs both DSB and LCD by recombination. Clone 02 has a linear dose response for high LET radiation. Starting from the same initial yieId frequency, wild-types have a sublinear response. The sublinear response reflects a smoothly decreasing probability that 'pinks' are generated as a function of increasing high LET dose for wild-type but not Clone 02. This smoothly decreasing response would be expected for LOH in 'wild-type' humans. It reflects an increasing proportion of DNA damage being repaired by non-recombinational pathways and/or an increasing probability of cell death with increasing dose. Clone 02 at low doses and low dose rates of low LET radiation has a linear dose response, reflecting a 1/16 probability of a lesion leading to LOH, relative to high LET lesions. This differential is held to reflect: microdosimetric differences in energy deposition and, therefore, DNA damage by low and high LET radiations; the effects of lesion clustering after high LET on the probability of generating the end wild-types. While no observations have been made at very low doses and dose rates in wild-types, there is no reason to suppose that the low LET linear non-threshold dose response of Clone 02 is abnormal. The importance of the LOH somatic genetic end-point is that it reflects cancer risk in humans. The linear non-threshold low dose low LET response curves reflects either the probability that recombinational Holliday junctions are occasionally cleaved in a rare orientation to generate LOH, or the probability that low LET lesions include a small proportion of clustered events similar to high LET ionization or both. Calculations of the Poisson probability that two or more low LET lesions will be induced in the same target suggest that dose rate effects depend upon the coincidence of DNA lesions in the same target, and that the probability of LOH depends upon lesion and repair factors. But the slope of LOH in Clone 02 and all other

Linear dose response curves in fungi and tradescantia

Energy Technology Data Exchange (ETDEWEB)

Unrau, P. [Atomic Energy of Canada Ltd., Chalk River, Ontario (Canada)

1999-07-15

;pink' loss of heterozygosity (LOH) events occur because Clone 02 repairs both DSB and LCD by recombination. Clone 02 has a linear dose response for high LET radiation. Starting from the same initial yieId frequency, wild-types have a sublinear response. The sublinear response reflects a smoothly decreasing probability that 'pinks' are generated as a function of increasing high LET dose for wild-type but not Clone 02. This smoothly decreasing response would be expected for LOH in 'wild-type' humans. It reflects an increasing proportion of DNA damage being repaired by non-recombinational pathways and/or an increasing probability of cell death with increasing dose. Clone 02 at low doses and low dose rates of low LET radiation has a linear dose response, reflecting a 1/16 probability of a lesion leading to LOH, relative to high LET lesions. This differential is held to reflect: microdosimetric differences in energy deposition and, therefore, DNA damage by low and high LET radiations; the effects of lesion clustering after high LET on the probability of generating the end wild-types. While no observations have been made at very low doses and dose rates in wild-types, there is no reason to suppose that the low LET linear non-threshold dose response of Clone 02 is abnormal. The importance of the LOH somatic genetic end-point is that it reflects cancer risk in humans. The linear non-threshold low dose low LET response curves reflects either the probability that recombinational Holliday junctions are occasionally cleaved in a rare orientation to generate LOH, or the probability that low LET lesions include a small proportion of clustered events similar to high LET ionization or both. Calculations of the Poisson probability that two or more low LET lesions will be induced in the same target suggest that dose rate effects depend upon the coincidence of DNA lesions in the same target, and that the probability of LOH depends upon lesion and repair factors. But the

Primary processes in radiation chemistry. LET (Linear Energy Transfer) effect in water radiolysis

International Nuclear Information System (INIS)

Trupin-Wasselin, V.

2000-01-01

The effect of ionizing radiations on aqueous solutions leads to water ionization and then to the formation of radical species and molecular products (e - aq , H . , OH . , H 2 O 2 , H 2 ). It has been shown that the stopping power, characterized by the LET value (Linear Energy Transfer) becomes different when the nature of the ionizing radiations is different. Few data are nowadays available for high LET radiations such as protons and high energy heavy ions. These particles have been used to better understand the primary processes in radiation chemistry. The yield of a chemical dosimeter (the Fricke dosimeter) and those of the hydrogen peroxide have been determined for different LET. The effect of the dose rate on the Fricke dosimeter yield and on the H 2 O 2 yield has been studied too. When the dose rate increases, an increase of the molecular products yield is observed. At very high dose rate, this yield decreases on account of the attack of the molecular products by radicals. The H 2 O 2 yield in alkaline medium decreases when the pH reaches 12. This decrease can be explained by a slowing down of the H 2 O 2 formation velocity in alkaline medium. Superoxide radical has also been studied in this work. A new detection method: the time-resolved chemiluminescence has been perfected for this radical. This technique is more sensitive than the absorption spectroscopy. Experiments with heavy ions have allowed to determine the O 2 .- yield directly in the irradiation cell. The experimental results have been compared with those obtained with a Monte Carlo simulation code. (O.M.)

The future of high-let radiation in cancer therapy. Justification of the heavy-ion therapy programmes

International Nuclear Information System (INIS)

Wambersie, A.

1989-01-01

The introduction of new types of ionizing radiations to control the primary tumour is a promising approach in radiation therapy. High-LET (linear energy transfer) radiations produce different biological effects compared to conventional X-rays, leading to a potential therapeutic advantage over low-LET (e.g., protons or helium ions) beams, which only are aimed at improving the physical selectivity. Introduced historically to reduce the OER (oxygen enhancement ratio), there is evidence for a reduction in radiosensitivity differences, which implies an advantage or disadvantage depending on the tumour characteristics and the normal tissues at risk, which in turn raises the problem of patient selection. From clinical data, fast neutrons were found to be superior to photons in the treatments of salivary gland tumours, prostatic adenocarcinomas, and some carcinomas. Heavy ions combine the advantages of a high physical selectivity and the potential advantage of high-LET for some tumour types. Clinical indications for the use of heavy-ion beams are therefore those tumours that reside in problematic sites but are of a type for which high-LET radiations were already shown to be useful. This review discusses the improvement of the physical selectivity with proton and helium ion beams; the differential effect and the potential advantage of neutrons and high-LET radiations (including both the radiological considerations and the clinical data); and presents the rationale for heavy-ion therapy. 38 refs, 7 figs, 10 tabs

Influence of high- and low-LET radiation on the cardiac differentiation of mouse embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Helm, Alexander

2013-07-19

The in utero exposure to ionising radiation poses a risk for the radiosensitive developing embryo. Effects of low-LET radiation on different developmental stages of the embryo are relatively well known due to experimental studies and epidemiological data. Data for effects on the very early stage of the embryonic development, particularly the effects of high-LET radiation instead are rather limited. However, unanticipated exposures of the early embryo to ionising radiation may occur through diagnostic or therapeutic applications or through radiation accidents. Additionally, protons and carbon ions are increasingly used in radiotherapy. Thus, a risk estimation of high-LET exposure especially to the early embryo is of a certain importance. To address this topic, pluripotent mouse embryonic stem cells resembling the blastocyst stage were irradiated with high-LET carbon ions or low-LET X-rays and subsequently differentiated to mimic the early embryonic development. The occurrence of spontaneously contracting cardiomyocytes was used as a marker to asses the radiation effects on the differentiation. Among others, cell inactivation, cell death and gene expression were analysed. A delay in the cardiac differentiation after radiation exposure was found. The results point to radiation-induced cell killing as the main effector of the developmental delay. Carbon ions were found to be more effective than X-rays.

Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness

International Nuclear Information System (INIS)

Schmid, T E; Zlobinskaya, O; Michalski, D; Molls, M; Multhoff, G; Greubel, C; Hable, V; Girst, S; Siebenwirth, C; Dollinger, G; Schmid, E

2012-01-01

This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm −1 ) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBE MN = 1.48 ± 0.07) and dicentrics (RBE D = 1.92 ± 0.15), in human–hamster hybrid (A L ) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm 2 matrix compared to quasi homogeneous in a 1 × 1 µm 2 matrix applied protons (RBE MN = 1.28 ± 0.07; RBE D = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a 12 C ion with 55 MeV total energy (4.48 MeV u −1 ). The enhancements are about half of that obtained for 12 C ions (RBE MN = 2.20 ± 0.06 and RBE D = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles. (paper)

Correct statistical evaluation for total dose in rural settlement

International Nuclear Information System (INIS)

Vlasova, N.G.; Skryabin, A.M.

2001-01-01

Statistical evaluation of dose reduced to the determination of an average value and its error. If an average value of a total dose in general can be determined by simple summarizing of the averages of its external and internal components, the evaluation of an error can be received only from its distribution. Herewith, considering that both components of the dose are interdependent, to summarize their distributions, as a last ones of a random independent variables, is incorrect. It follows that an evaluation of the parameters of the total dose distribution, including an error, in general, cannot be received empirically, particularly, at the lack or absence of the data on one of the components of the last one, that constantly is happens in practice. If the evaluation of an average for total dose was defined somehow, as the best, as an average of a distribution of the values of individual total doses, as summarizing the individual external and internal doses by the random type, that an error of evaluation had not been produced. The methodical approach to evaluation of the total dose distribution at the lack of dosimetric information was designed. The essence of it is original way of an interpolation of an external dose distribution, using data on an internal dose

Analysis of complex-type chromosome exchanges in astronauts' lymphocytes after space flight as a biomarker of high-LET exposure

International Nuclear Information System (INIS)

George, K.; Wu, H.; Willingham, V.; Cucinotta, F.A.

2002-01-01

High-linear energy transfer (LET) radiation is moreefficient in producing complex-type chromosome exchanges than sparsely ionizing radiation, and this can potentially be used as a biomarker of radiation quality. To investigate if complex chromosome exchanges are induced by the high-LET component of space radiation exposure, damage was assessed in astronauts' blood lymphocytes before and after longduration missions of 3-4 months. The frequency of simple translocations increased significantly for most of the crewmembers studied. However, there were few complex exchanges detected and only one crewmember had a significant increase after flight. It has been suggested that the yield of complex chromosome damage could be underestimated when analyzing metaphase cellscollected at one time point after irradiation, andanalysis of chemically-induced premature chromosomecondensation (PCC) may be more accurate since problems with complicated cell-cycle delays are avoided.However, in this case the yields of chromosome damage were similar for metaphase and PCC analysis of astronauts' lymphocytes. It appears that the use of complex-type exchanges as biomarkerof radiation quality in vivo after low-dose chronicexposure in mixed radiation fields is hampered by statistical uncertainties. (author)

Dosimetry and LET spectrometry in C 290 MeV/n and Ne 400 MeV/n HIMAC ion beam by different TLD's, TED based LET spectrometers, and Si energy-deposition spectrometer

International Nuclear Information System (INIS)

Spurny, F.; Brabcova, K.; Jadrnickova, I.; Uchihori, Y.; Kitamura, H.; Yasuda, N.; Molokanov, A. G.

2009-01-01

The sets of track etched detectors based (TED) spectrometer's of the linear energy transfer (LET) have been, together with two types of thermoluminescent detectors (TLD)and MDU- Liulin energy deposition spectrometer exposed in the C 290 MeV/n and Ne 400 MeV/n ion beams at the HlMAC installation at NIRS, Chiba, Japan. The experiment has been performed in the frame of NPI project 20P241 agreed by HlMAC P AC at the beginning of 2008 year. Up to now, moxstle only results obtained in C-ion beam have been treated and analyzed. Sets of TED spectrometer's and TLD detectors have been exposed in 19 depths in the C-ion beam with expected LET values of primary particles from 13 keV/μm in water, through the Bragg peak area up to two depth behind the Bragg peak. The contribution of fragments to total number of events, and to the energy absorbed in Si has been determined, when possible separately for different fragments. In all cases also total contribution of fragments (and other secondary particles) to the total number of energy deposition events and to the absorbed dose has been estimated. LET and energy deposition spectra obtained will be compared together , a good agreement of data has bee stated. Some of results have been also compared with those obtained by calculation by means of PHITS code. (authors)

Effects of low doses; Effet des faibles doses

Energy Technology Data Exchange (ETDEWEB)

Le Guen, B. [Electricite de France (EDF-LAM-SCAST), 93 - Saint-Denis (France)

2001-07-01

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

Water radiolysis in extreme conditions of temperature and LET. Scavenging of HO. by Br- ions

International Nuclear Information System (INIS)

Saffre, Dimitri

2011-01-01

The purpose of this thesis is to contribute to the understanding of the oxidation mechanism of Br - in which the HO . radical is involved. The HO . radiolytic yield is strongly connected with the oxidation yield of Br - , and therefore we have studied the influence of different physical and chemical parameters on this global yield: temperature, LET, dose rate, pH, saturation gas. The solutions have been irradiated with 4 types of ionizing rays: X-rays (from 13 to 18 keV), electrons (from 7 to 10 MeV), C 6+ -ions beam of 975 MeV and He 2+ -ions beam of 70 MeV. The development of an optical autoclave with solution flow, compatible with high LET ionizing rays has allowed us conduct the first experiments at constant high LET and high temperature. This cell has turned out to be compatible with the picosecond pump-probe experiments performed with the ELYSE accelerator. The HO . scavenging yield has been, therefore, estimated at both high LET and high temperature. A better understanding of the Br - oxidation mechanism has been achieved, in acid medium, in particular, by comparing the kinetics results with Monte Carlo Simulations for time scales inferior to the microsecond and with Chemsimul for the stable products (Br 2 .- and Br 3 - formations). (author) [fr

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-11-01

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

Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System

Science.gov (United States)

Alwood, Joshua S.; Tran, Luan H.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Kumar, Akhilesh; Hilton, Diane; Tahimic, Candice G. T.; Globus, Ruth

2017-01-01

Exposure to space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized exposure to ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-week old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 mega electron volts per nucleon) or high-LET (sup 56) Fe ions (600 mega electron volts per nucleon) using either low (5 or 10 centigrays) or high (50 or 200 centigrays) doses at NASAs Space Radiation Lab at Brookhaven National Lab (NSRL/BNL). Tissues were harvested 5 weeks or 1 year after irradiation and bones were analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed for select groups by RT-PCR (Reverse Transcription-Polymerase Chain Reaction) during the proliferative phase or the mineralizing phase, and differentiation was analyzed by imaging mineralized nodules (percentage surface area). Representative genes were selected for expression analyses, including cell proliferation (PCNA, Cdk2, p21, p53), differentiation (Runx2, Alpl, Bglap), oxidative metabolism (Catalase, GPX, MnSOD, CuZnSOD, iNos, Foxo1), DNA-damage repair (Gadd45), or apoptosis (Caspase 3). As expected, a high dose (200 centigrays), but not low doses, of either (sup 56) Fe or protons caused a loss of cancellous bone volume per total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; (sup 56) Fe (200 centigrays) inhibited median nodule area by more than 90 percent at 5 weeks and 1 year post-irradiation, compared to controls. At 5 weeks post

Results of Hematopoietic Stem Cell Transplantation After Treatment With Different High-Dose Total-Body Irradiation Regimens in Five Dutch Centers

International Nuclear Information System (INIS)

Loes van Kempen-Harteveld, M.; Brand, Ronald; Kal, Henk B.; Verdonck, Leo F.; Hofman, Pieter; Schattenberg, Anton V.; Maazen, Richard W. van der; Cornelissen, Jan J.; Eijkenboom, Wil M.H.; Lelie, Johannes P. van der; Oldenburger, Foppe; Barge, Renee M.; Biezen, Anja van; Vossen, Jaak M.J.J.; Noordijk, Evert M.; Struikmans, Henk

2008-01-01

Purpose: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. Methods and Materials: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia and non-Hodgkin's lymphoma. The TBI regimens were normalized by using the biological effective dose (BED) concept. The BED values were divided into three dose groups. Study end points were relapse incidence (RI), non-relapse mortality (NRM), relapse-free survival (RFS), and overall survival (OS). Multivariate analysis was performed, stratified by disease. Results: In the highest TBI dose group, RI was significantly lower and NRM was higher vs. the lower dose groups. However, a significant influence on RFS and OS was not found. Relapses in the eye region were found only after shielding to very low doses. Age was of significant influence on OS, RFS, and NRM in favor of younger patients. The NRM of patients older than 40 years significantly increased, and OS decreased. There was no influence of age on RI. Men had better OS and RFS and lower NRM. Type of transplantation significantly influenced RI and NRM for patients with acute leukemia and non-Hodgkin's lymphoma. There was no influence on RFS and OS. Conclusions: Both RI and NRM were significantly influenced by the size of the BED of single-dose or two-fraction TBI regimens; OS and RFS were not. Age was of highly significant influence on NRM, but there was no influence of age on RI. Hyperfractionated TBI with a high BED might be useful, assuming NRM can be reduced

Theoretic simulation for CMOS device on total dose radiation response

International Nuclear Information System (INIS)

He Baoping; Zhou Heqin; Guo Hongxia; He Chaohui; Zhou Hui; Luo Yinhong; Zhang Fengqi

2006-01-01

Total dose effect is simulated for C4007B, CC4007RH and CC4011 devices at different absorbed dose rate by using linear system theory. When irradiation response and dose are linear, total dose radiation and post-irradiation annealing at room temperature are determined for one random by choosing absorbed dose rate, and total dose effect at other absorbed dose rate can be predicted by using linear system theory. The simulating results agree with the experimental results at different absorbed dose rate. (authors)

Fiber optics in high dose radiation fields

International Nuclear Information System (INIS)

Partin, J.K.

1985-01-01

A review of the behavior of state-of-the-art optical fiber waveguides in high dose (greater than or equal to 10 5 rad), steady state radiation fields is presented. The influence on radiation-induced transmission loss due to experimental parameters such as dose rate, total dose, irradiation history, temperature, wavelength, and light intensity, for future work in high dose environments are given

ELDRS Characterization for a Very High Dose Mission

Science.gov (United States)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

2010-01-01

Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

Effect on pancreatic beta cells and nerve cells by low let x-ray

Energy Technology Data Exchange (ETDEWEB)

Park, Kwang Hun [Dept. of Nuclear Medicine, Kyungbuk National University Hospital, Daegu (Korea, Republic of); Kim, Kgu Hwan [Dept. of Radiological Technology, Daegu health College, Daegu (Korea, Republic of)

2014-03-15

Cultured pancreatic beta cells and nerve cells, it is given normal condition of 10% FBS (fetal bovine serum), 11.1 mM glucose and hyperglycemia condition of 1% FBS, 30 mM glucose. For low LET X-ray irradiated with 0.5 Gy/hr dose-rate(total dose: 0.5 to 5 Gy). Survival rates were measured by MTT assay. When non irradiated, differentiated in the pancreatic beta cells experiment is hyperglycemia conditions survival rate compared to normal conditions survival rate seemed a small reduction. However increasing the total dose of X-ray, the survival rate of normal conditions decreased slightly compared to the survival rate of hyperglycemia conditions, the synergistic effect was drastically reduced. When non irradiated, undifferentiated in the nerve cells experiment is hyperglycemia conditions survival rate compared to normal conditions survival rate seemed a large reduction. As the cumulative dose of X-ray normal conditions and hyperglycemia were all relatively rapid cell death. But the rate of decreased survivals by almost parallel to the reduction proceed and it didn't show synergistic effect.

Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

International Nuclear Information System (INIS)

Healy, W.L.; Lo, T.C.; Covall, D.J.; Pfeifer, B.A.; Wasilewski, S.A.

1990-01-01

Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700 centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy

LET effects on normal and radiosensitive cell lines

International Nuclear Information System (INIS)

Geard, C.R.; Travisano, M.

1986-01-01

Charged particles in the track segment mode were produced by the RARAF Van de Graaff accelerator and used to irradiate two CHO cell lines, a radiosensitive hypermutable line EM9 and its normal parent AA8. Asynchronous cells were irradiated attached to 6 micrometer thick Mylar with protons, deuterons and helium-3 particles at LETs ranging from 10 to 150 keV per micrometer. A 50 kVp x-ray tube integrated into the track segment facility provided a low LET comparison. Following irradiation cells were monitored for clonogenicity, and in a separate series of experiments frequencies of sister chromatid exchanges. Up to 9 experiments were carried out at each LET, with a total of 8 radiations of different LETs being compared. The optimally effective LET for cell survival was between 80 and 120 keV per micrometer, with the 150 keV per micrometer particles indicating energy wastage. The differential between the normal and radiosensitive cell lines was maintained at all LETs

Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation

Energy Technology Data Exchange (ETDEWEB)

Nakagawa, Yosuke [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Takahashi, Akihisa [Advanced Scientific Research Leader Development Unit, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Kajihara, Atsuhisa; Yamakawa, Nobuhiro; Imai, Yuichiro [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ota, Ichiro; Okamoto, Noritomo [Department of Otorhinolaryngology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Mori, Eiichiro [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Noda, Taichi [Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Furusawa, Yoshiya [Heavy-ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kirita, Tadaaki [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ohnishi, Takeo, E-mail: tohnishi@naramed-u.ac.jp [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan)

2012-07-13

Highlights: Black-Right-Pointing-Pointer High-LET radiation induces efficiently apoptosis regardless of p53 gene status. Black-Right-Pointing-Pointer We examined whether high-LET radiation depresses the Akt-survival signals. Black-Right-Pointing-Pointer High-LET radiation depresses of survival signals even in the mp53 cancer cells. Black-Right-Pointing-Pointer High-LET radiation activates Caspase-9 through depression of survival signals. Black-Right-Pointing-Pointer High-LET radiation suppresses cell growth through depression of survival signals. -- Abstract: Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6 h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G{sub 2}/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp

Yields of clustered DNA damage induced by charged-particle radiations of similar kinetic energy per nucleon: LET dependence in different DNA microenvironments

International Nuclear Information System (INIS)

Keszenman, D.J.; Sutherland, B.M.

2010-01-01

To determine the linear energy transfer (LET) dependence of the biological effects of densely ionizing radiation in relation to changes in the ionization density along the track, we measured the yields and spectrum of clustered DNA damages induced by charged particles of different atomic number but similar kinetic energy per nucleon in different DNA microenvironments. Yeast DNA embedded in agarose in solutions of different free radical scavenging capacity was irradiated with 1 GeV protons, 1 GeV/nucleon oxygen ions, 980 MeV/nucleon titanium ions or 968 MeV/nucleon iron ions. The frequencies of double-strand breaks (DSBs), abasic sites and oxypurine clusters were quantified. The total DNA damage yields per absorbed dose induced in non-radioquenching solution decreased with LET, with minor variations in radioquenching conditions being detected. However, the total damage yields per particle fluence increased with LET in both conditions, indicating a higher efficiency per particle to induce clustered DNA damages. The yields of DSBs and non-DSB clusters as well as the damage spectra varied with LET and DNA milieu, suggesting the involvement of more than one mechanism in the formation of the different types of clustered damages.

Effect of high-dose preoperative methylprednisolone on recovery after total hip arthroplasty

DEFF Research Database (Denmark)

Lunn, T H; Andersen, Lasse Østergaard; Kristensen, B B

2013-01-01

(IQR) (95% CI), MP vs placebo]: 23.5 (23.3-23.7) (17.8-43.8) vs 23.5 (23.0-23.8) (20.0-46.8) h, the mean difference (95% CI) being -1.3 (-4.7 to 2.2) h, P=0.65. Overall pain for the first 24 h after surgery was significantly reduced in the MP vs the placebo group (PMP 125 mg i.v. before surgery added......BACKGROUND: /st>High-dose glucocorticoid may reduce postsurgical pain and improve recovery. We hypothesized that 125 mg methylprednisolone (MP) would reduce time to meet functional discharge criteria after total hip arthroplasty (THA). METHODS: /st>Forty-eight patients undergoing unilateral THA...... under spinal anaesthesia were consecutively included in this randomized, double-blind, placebo-controlled trial receiving preoperative i.v. MP or saline. All patients received a standardized, multimodal analgesic regime with paracetamol, celecoxib, and gabapentin. The primary outcome was time to meet...

Molecular nature of mutations induced by high-LET irradiation with argon and carbon ions in Arabidopsis thaliana

International Nuclear Information System (INIS)

Hirano, Tomonari; Kazama, Yusuke; Ohbu, Sumie; Shirakawa, Yuki; Liu Yang; Kambara, Tadashi; Fukunishi, Nobuhisa; Abe, Tomoko

2012-01-01

Linear energy transfer (LET) is an important parameter to be considered in heavy-ion mutagenesis. However, in plants, no quantitative data are available on the molecular nature of the mutations induced with high-LET radiation above 101–124 keV μm −1 . In this study, we irradiated dry seeds of Arabidopsis thaliana with Ar and C ions with an LET of 290 keV μm −1 . We analyzed the DNA alterations caused by the higher-LET radiation. Mutants were identified from the M 2 pools. In total, 14 and 13 mutated genes, including bin2, egy1, gl1, gl2, hy1, hy3–5, ttg1, and var2, were identified in the plants derived from Ar- and C-ions irradiation, respectively. In the mutants from both irradiations, deletion was the most frequent type of mutation; 13 of the 14 mutated genes from the Ar ion-irradiated plants and 11 of the 13 mutated genes from the C ion-irradiated plants harbored deletions. Analysis of junction regions generated by the 2 types of irradiation suggested that alternative non-homologous end-joining was the predominant pathway of repair of break points. Among the deletions, the proportion of large deletions (>100 bp) was about 54% for Ar-ion irradiation and about 64% for C-ion irradiation. Both current results and previously reported data revealed that the proportions of the large deletions induced by 290-keV μm −1 radiations were higher than those of the large deletions induced by lower-LET radiations (6% for 22.5–30.0 keV μm −1 and 27% for 101–124 keV μm −1 ). Therefore, the 290 keV μm −1 heavy-ion beams can effectively induce large deletions and will prove useful as novel mutagens for plant breeding and analysis of gene functions, particularly tandemly arrayed genes.

Molecular nature of mutations induced by high-LET irradiation with argon and carbon ions in Arabidopsis thaliana

Energy Technology Data Exchange (ETDEWEB)

Hirano, Tomonari; Kazama, Yusuke [Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Innovation Center, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Ohbu, Sumie; Shirakawa, Yuki; Liu Yang; Kambara, Tadashi; Fukunishi, Nobuhisa [Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Abe, Tomoko, E-mail: tomoabe@riken.jp [Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Innovation Center, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

2012-07-01

Linear energy transfer (LET) is an important parameter to be considered in heavy-ion mutagenesis. However, in plants, no quantitative data are available on the molecular nature of the mutations induced with high-LET radiation above 101-124 keV {mu}m{sup -1}. In this study, we irradiated dry seeds of Arabidopsis thaliana with Ar and C ions with an LET of 290 keV {mu}m{sup -1}. We analyzed the DNA alterations caused by the higher-LET radiation. Mutants were identified from the M{sub 2} pools. In total, 14 and 13 mutated genes, including bin2, egy1, gl1, gl2, hy1, hy3-5, ttg1, and var2, were identified in the plants derived from Ar- and C-ions irradiation, respectively. In the mutants from both irradiations, deletion was the most frequent type of mutation; 13 of the 14 mutated genes from the Ar ion-irradiated plants and 11 of the 13 mutated genes from the C ion-irradiated plants harbored deletions. Analysis of junction regions generated by the 2 types of irradiation suggested that alternative non-homologous end-joining was the predominant pathway of repair of break points. Among the deletions, the proportion of large deletions (>100 bp) was about 54% for Ar-ion irradiation and about 64% for C-ion irradiation. Both current results and previously reported data revealed that the proportions of the large deletions induced by 290-keV {mu}m{sup -1} radiations were higher than those of the large deletions induced by lower-LET radiations (6% for 22.5-30.0 keV {mu}m{sup -1} and 27% for 101-124 keV {mu}m{sup -1}). Therefore, the 290 keV {mu}m{sup -1} heavy-ion beams can effectively induce large deletions and will prove useful as novel mutagens for plant breeding and analysis of gene functions, particularly tandemly arrayed genes.

Description and verification of an algorithm for obtaining microdosimetric quantities for high-LET radiation using a single TEPC without pulse height analysis.

Science.gov (United States)

Borak, Thomas B; Chapman, Phillip L

2014-10-01

Microdosimetric spectra of single event distributions have been used to provide estimates of quality factors for radiation protection of high-LET radiation. In situations with high-dose rates it becomes difficult to measure, record and store energy deposition from single events. An alternative approach is to store random energy deposition events in a sequence of fixed time intervals that does not require identifying from single events. This can be accomplished with a single detector without pulse height analysis. We show the development of the algorithm using expectation analysis of the statistical estimators for moments of lineal energy: ȳf and ȳD. The method was tested using Monte Carlo simulations based on single event distributions measured with spherical tissue equivalent proportional counters where the event sizes spanned more than two orders of magnitude. The evaluation included testing at various mean numbers of events per interval (i.e., dose rate) and numbers of intervals (i.e., total duration). Results of the expectation analysis and Monte Carlo simulation showed that the algorithm corrects for the excess dispersion due to the random number of events in each time interval when the underlying dose rate is constant. It also converges to the correct value when there is a linear trend in dose rate of the duration of the measurement process. Although this system is not applicable for pulsed radiation fields it proved to be robust when applied to measured distributions with single event spectra (PuBe neutrons, Fe ions at 1,000 MeV/nucleon and a power function distribution of single event sizes) with a coefficient of variation of 25% for estimates of ȳD using 100 sampling intervals and 10% using 400 sampling intervals.

Total dose induced latch in short channel NMOS/SOI transistors

International Nuclear Information System (INIS)

Ferlet-Cavrois, V.; Quoizola, S.; Musseau, O.; Flament, O.; Leray, J.L.; Pelloie, J.L.; Raynaud, C.; Faynot, O.

1998-01-01

A latch effect induced by total dose irradiation is observed in short channel SOI transistors. This effect appears on NMOS transistors with either a fully or a partially depleted structure. It is characterized by a hysteresis behavior of the Id-Vg characteristics at high drain bias for a given critical dose. Above this dose, the authors still observe a limited leakage current at low drain bias (0.1 V), but a high conduction current at high drain bias (2 V) as the transistor should be in the off-state. The critical dose above which the latch appears strongly depends on gate length, transistor structure (fully or partially depleted), buried oxide thickness and supply voltage. Two-dimensional (2D) numerical simulations indicate that the parasitic condition is due to the latch of the back gate transistor triggered by charge trapping in the buried oxide. To avoid the latch induced by the floating body effect, different techniques can be used: doping engineering, body contacts, etc. The study of the main parameters influencing the latch (gate length, supply voltage) shows that the scaling of technologies does not necessarily imply an increased latch sensitivity. Some technological parameters like the buried oxide hardness and thickness can be used to avoid latch, even at high cumulated dose, on highly integrated SOI technologies

SU-F-T-239: Evaluation of Plastic Scintillator Light Output for Various Lead Doping Concentrations: Towards LET Detection

International Nuclear Information System (INIS)

Nusrat, H; Pang, G; Sarfehnia, A

2016-01-01

Purpose: This work seeks to develop a beam quality meter using multiple differently doped plastic scintillators that are thus intrinsically beam-quality dependent. Plastic scintillators spontaneously emit visible light upon irradiation; the amount of light produced is dependent on stopping power (closely related to LET) according to Birks’ law. Doping plastic scintillators can be used to tune their sensitivity to specific LET ranges. Methods: GEANT4.10.1 Monte Carlo (MC) was used to evaluate the response of various scintillator dopant combinations. MC radiation transport and scintillator light response were validated against previously published literature. Current work involves evaluating detector response experimentally; to that end, a detector prototype with interchangeable scintillator housing was constructed. Measurement set-up guides light emitted by the scintillator to a photomultiplier tube via a glass taper junction coupled to an optical fiber. The resulting signal is measured by an electrometer, and normalized to dose readout from a diode. Measurements have been done using clinical electron and orthovoltage beams. MC response (simulated scintillator light normalized to dose scored inside the scintillating volume) was evaluated for four different LET radiations for an undoped and 1%Pb doped scintillator (σ=0.85%). Simulated incident electrons included: 0.05, 0.1, 0.2, 6, 12, and 18 MeV; these energies correspond to a range of stopping power (related to LET) values ranging from 1.824 to 11.09 MeVcm"2g"−"1 (SCOL from NIST-ESTAR). Results: Initial MC results show a distinct divergence in scintillator response as LET increases. The response for undoped plastic scintillator indicated a 35.0% increase in signal when going from 18 MeV (low LET) to 0.05 MeV (high LET) while 1%-Pb doped scintillator indicated a 100.9% increase. Conclusion: After validating MC against measurement, simulations will be used to test various concentrations (2%, 4%, 6%) of different

SU-F-T-239: Evaluation of Plastic Scintillator Light Output for Various Lead Doping Concentrations: Towards LET Detection

Energy Technology Data Exchange (ETDEWEB)

Nusrat, H [Ryerson University, Toronto, ON (Canada); Pang, G; Sarfehnia, A [Sunnybrook Health Sciences Centre, Toronto, ON (Canada)

2016-06-15

Purpose: This work seeks to develop a beam quality meter using multiple differently doped plastic scintillators that are thus intrinsically beam-quality dependent. Plastic scintillators spontaneously emit visible light upon irradiation; the amount of light produced is dependent on stopping power (closely related to LET) according to Birks’ law. Doping plastic scintillators can be used to tune their sensitivity to specific LET ranges. Methods: GEANT4.10.1 Monte Carlo (MC) was used to evaluate the response of various scintillator dopant combinations. MC radiation transport and scintillator light response were validated against previously published literature. Current work involves evaluating detector response experimentally; to that end, a detector prototype with interchangeable scintillator housing was constructed. Measurement set-up guides light emitted by the scintillator to a photomultiplier tube via a glass taper junction coupled to an optical fiber. The resulting signal is measured by an electrometer, and normalized to dose readout from a diode. Measurements have been done using clinical electron and orthovoltage beams. MC response (simulated scintillator light normalized to dose scored inside the scintillating volume) was evaluated for four different LET radiations for an undoped and 1%Pb doped scintillator (σ=0.85%). Simulated incident electrons included: 0.05, 0.1, 0.2, 6, 12, and 18 MeV; these energies correspond to a range of stopping power (related to LET) values ranging from 1.824 to 11.09 MeVcm{sup 2}g{sup −1} (SCOL from NIST-ESTAR). Results: Initial MC results show a distinct divergence in scintillator response as LET increases. The response for undoped plastic scintillator indicated a 35.0% increase in signal when going from 18 MeV (low LET) to 0.05 MeV (high LET) while 1%-Pb doped scintillator indicated a 100.9% increase. Conclusion: After validating MC against measurement, simulations will be used to test various concentrations (2%, 4%, 6%) of

The carcinogenic risk of high dose total body irradiation in non-human primates

International Nuclear Information System (INIS)

Broerse, J.J.; Bartstra, R.W.; Bekkum, D.W. van; Hage, M.H. van der; Zurcher, C.; Zwieten, M.J. van; Hollander, C.F.

2000-01-01

High dose total body irradiation (TBI) in combination with chemotherapy, followed by rescue with bone marrow transplantation (BMT), is increasingly used for the treatment of haematological malignancies. With the increasing success of this treatment and its current introduction for treating refractory autoimmune diseases the risk of radiation carcinogenesis is of growing concern. Studies on turnout induction in non-human primates are of relevance in this context since the response of this species to radiation does not differ much from that in man. Since the early sixties, studies have been performed on acute effects in Rhesus monkeys and the protective action of bone marrow transplantation after irradiation with X-rays (average total body dose 6.8 Gy) and fission neutrons (average dose 3.4 Gy). Of those monkeys, which were irradiated and reconstituted with autologous bone marrow, 20 animals in the X-irradiated group and nine animals in the neutron group survived more than 3 years. A group of 21 non-irradiated Rhesus monkeys of a comparable age distribution served as controls. All animals were regularly screened for the occurrence of neoplasms. Complete necropsies were performed after natural death or euthanasia. At post-irradiation intervals of 4-21 years an appreciable number of tumours was observed. In the neutron irradiated group eight out of nine animals died with one or more malignant tumours. In the X-irradiated group this fraction was 10 out of 20. The tumours in the control group, in seven out of the 21 animals, appeared at much older a-e compared with those in the irradiated cohorts. The histogenesis of the tumours was diverse with a preponderance of renal carcinoma, sarcomas among which osteosarcormas, and malignant glomus tumours in the irradiated groups. When corrected for competing risks, the carcinogenic risk of TBI in the Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a

Prophage λ induction by ionizing radiation of different LETs

International Nuclear Information System (INIS)

Bonev, M.N.; Kozubek, S.; Krasavin, E.A.; Amirtaev, K.G.

1988-01-01

The λ prophage induction caused by γ-irradiation and accelerated heavy ions with different LET was studied in variety Escherichia coli strains. The induction frequency on the dose I(D) shaped a curve with a maximum in the strains which possess recA + /lexA + genotype. The inductivity of these strains increases as well as LET and an alteration poor → rich media does it. Unlike I(D) for recA + /lexA + , the dependence I(D) for recA, lexA and recBC strains was a constant. 15 refs.; 6 figs.; 3 tabs

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

International Nuclear Information System (INIS)

Wang Jufang; Lu Dong; Wu Xin; Sun Haining; Ma Shuang; Li Renmin; Li Wenjian

2010-01-01

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV μm -1 ) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV μm -1 . The mutation cross section saturated when LET was higher than 58.2 keV μm -1 . Meanwhile, the highest RBE i for inactivation located at 120.0 keV μm -1 and the highest RBE m for mutation was at 58.2 keV μm -1 . The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

Science.gov (United States)

Wang, Jufang; Lu, Dong; Wu, Xin; Sun, Haining; Ma, Shuang; Li, Renmin; Li, Wenjian

2010-09-01

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV μm -1) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV μm -1. The mutation cross section saturated when LET was higher than 58.2 keV μm -1. Meanwhile, the highest RBE i for inactivation located at 120.0 keV μm -1 and the highest RBE m for mutation was at 58.2 keV μm -1. The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

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

International Nuclear Information System (INIS)

Tomita, Masanori; Maeda, Munetoshi

2015-01-01

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 by-stander 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. (author)

Low LET radiolysis escape yields for reducing radicals and H2 in pressurized high temperature water

Science.gov (United States)

Sterniczuk, Marcin; Yakabuskie, Pamela A.; Wren, J. Clara; Jacob, Jasmine A.; Bartels, David M.

2016-04-01

Low Linear Energy Transfer (LET) radiolysis escape yields (G values) are reported for the sum (G(radH)+G(e-)aq) and for G(H2) in subcritical water up to 350 °C. The scavenger system 1-10 mM acetate/0.001 M hydroxide/0.00048 M N2O was used with simultaneous mass spectroscopic detection of H2 and N2 product. Temperature-dependent measurements were carried out with 2.5 MeV electrons from a van de Graaff accelerator, while room temperature calibration measurements were done with a 60Co gamma source. The concentrations and dose range were carefully chosen so that initial spur chemistry is not perturbed and the N2 product yield corresponds to those reducing radicals that escape recombination in pure water. In comparison with a recent review recommendation of Elliot and Bartels (AECL report 153-127160-450-001, 2009), the measured reducing radical yield is seven percent smaller at room temperature but in fairly good agreement above 150 °C. The H2 escape yield is in good agreement throughout the temperature range with several previous studies that used much larger radical scavenging rates. Previous analysis of earlier high temperature measurements of Gesc(radOH) is shown to be flawed, although the actual G values may be nearly correct. The methodology used in the present report greatly reduces the range of possible error and puts the high temperature escape yields for low-LET radiation on a much firmer quantitative foundation than was previously available.

Effect of γ-dose rate and total dose interrelation on the polymeric hydrogel: A novel injectable male contraceptive

International Nuclear Information System (INIS)

Jha, Pradeep K.; Jha, Rakhi; Gupta, B.L.; Guha, Sujoy K.

2010-01-01

Functional necessity to use a particular range of dose rate and total dose of γ-initiated polymerization to manufacture a novel polymeric hydrogel RISUG (reversible inhibition of sperm under guidance) made of styrene maleic anhydride (SMA) dissolved in dimethyl sulphoxide (DMSO), for its broad biomedical application explores new dimension of research. The present work involves 16 irradiated samples. They were tested by fourier transform infrared spectroscopy, matrix assisted laser desorption/ionization-TOF, field emission scanning electron microscopy, high resolution transmission electron microscopy, etc. to see the interrelation effect of gamma dose rates (8.25, 17.29, 20.01 and 25.00 Gy/min) and four sets of doses (1.8, 2.0, 2.2 and 2.4 kGy) on the molecular weight, molecular weight distribution and porosity analysis of the biopolymeric drug RISUG. The results of randomized experiment indicated that a range of 18-24 Gy/min γ-dose rate and 2.0-2.4 kGy γ-total doses is suitable for the desirable in vivo performance of the contraceptive copolymer.

The induction of somatic mutations by high-LET radiations using the drosophila assay system

International Nuclear Information System (INIS)

Yoshikawa, Isao; Takatsuji, Toshihiro

2004-01-01

Two types of somatic mutation in Drosophila melanogaster were examined to evaluate the relative biological effectiveness (RBE) of 252 Cf neutrons and heavy ions (carbon ions and neon ions) accelerated with a synchrotron for inducing mutations as a function of linear energy transfer (LET). One is the loss of heterozygosity for wing-hair mutations and the other the reversion of the mutant white-ivory. The measurements were made using a combined mutation assay system; so that induced mutant wing-hair clones as well as revertant eye-color clones could be detected simultaneously in the same fly. Larvae were irradiated at the age of 3 days post-oviposition. The efficiency of 252 Cf neutrons for inducing wing-hair mosaic spots is very high, RBE=8.5, but that for eye-color mosaic spot is almost equal (RBE=1.2) to that of 137 Cs γ-rays. RBE-LET relationships were obtained for the induction of wing-hair and eye-color mosaic spots. The RBE of carbon and neon ions for producing wing-hair mosaic spots increased with increasing LET values. The RBE for the induction of eye-color mutants did not change with LET. These relationships suggest that more complex types of DNA damage such as non-rejoinable strand breaks or clustered double strand breaks that increase with LET may be responsible for inducing the wing-hair mutation, while simpler forms of molecular damage may induce reversion in the white-ivory allele. (author)

Targeting DNA repair with PNKP inhibition sensitizes radioresistant prostate cancer cells to high LET radiation.

Directory of Open Access Journals (Sweden)

Pallavi Srivastava

Full Text Available High linear energy transfer (LET radiation or heavy ion such as carbon ion radiation is used as a method for advanced radiotherapy in the treatment of cancer. It has many advantages over the conventional photon based radiotherapy using Co-60 gamma or high energy X-rays from a Linear Accelerator. However, charged particle therapy is very costly. One way to reduce the cost as well as irradiation effects on normal cells is to reduce the dose of radiation by enhancing the radiation sensitivity through the use of a radiomodulator. PNKP (polynucleotide kinase/phosphatase is an enzyme which plays important role in the non-homologous end joining (NHEJ DNA repair pathway. It is expected that inhibition of PNKP activity may enhance the efficacy of the charged particle irradiation in the radioresistant prostate cancer cell line PC-3. To test this hypothesis, we investigated cellular radiosensitivity by clonogenic cell survival assay in PC-3 cells.12Carbon ion beam of62 MeVenergy (equivalent 5.16 MeV/nucleon and with an entrance LET of 287 kev/μm was used for the present study. Apoptotic parameters such as nuclear fragmentation and caspase-3 activity were measured by DAPI staining, nuclear ladder assay and colorimetric caspase-3method. Cell cycle arrest was determined by FACS analysis. Cell death was enhanced when carbon ion irradiation is combined with PNKPi (PNKP inhibitor to treat cells as compared to that seen for PNKPi untreated cells. A low concentration (10μM of PNKPi effectively radiosensitized the PC-3 cells in terms of reduction of dose in achieving the same survival fraction. PC-3 cells underwent significant apoptosis and cell cycle arrest too was enhanced at G2/M phase when carbon ion irradiation was combined with PNKPi treatment. Our findings suggest that combined treatment of carbon ion irradiation and PNKP inhibition could enhance cellular radiosensitivity in a radioresistant prostate cancer cell line PC-3. The synergistic effect of PNKPi

The radiochromic dye film dose meter as a possible test of particle track theory

International Nuclear Information System (INIS)

Hansen, J.W.; Jensen, M.; Katz, R.

1980-09-01

The response characteristic of the thin-film radiometric dye cyanide plastic dose meter to ionizing radiation of electrons and heavy charged particles is investigated as a possible test of the particle track theory worked out by Robert Katz and coworkers. Dose response curves for low-LET radiation have been investigated and are used for a quality estimation of the response for protons and oxygen ions at 16 and 4 MeV/amu, respectively. A bleaching effect on the colouration at high doses intimates that the target cannot be interpreted lieerally, but it might still be possinle to transfer the function of the macroscopic dose response to a theoretical dose response curve in a microscopic scale for a single ion. From this relation the macroscopic dose response curve can be determined qhen the film is irradiated with heavy ions. It will be shown theoretically that for protons there is no saturation in the track core, whereas calculations for oxygen ions show a heavy saturation in the track core, which means that a part of the ions loose their energy ineffectively. We can conclude that itis possible qualitatively to predict the dose response curve for high-LET particles by means of the dose response curve for low-LET radiation. (author)

The induction of somatic mutations by high-LET radiation observed using the Drosophila assay system

International Nuclear Information System (INIS)

Yoshikawa, Isao; Takatsuji, Toshihiro; Nagano, Masaaki; Hoshi, Masaharu; Takada, Jun; Endo, Satoru

1999-01-01

To evaluate the mutagenic potential of high-LET radiation, an analysis was made on the production of somatic mutations by 252 Cf fission neutron s and heavy particle ions accelerated by a synchrotron. A Drosophila strain that allows simultaneous detection of two types of mutations in an identical fly was constructed. One was a wing-hair mutation and the other was an eye-color mosaic spot mutation. Measurements were made using a combined assay system of both mutation assays. Larvae were exposed to radiation at the age of post-ovipositional day-3. The efficiency of 252 Cf neutrons for inducing wing-hair mosaic spots was very high, the relative biological effectiveness (RBE) = 8.5, but the efficiency for eye-color mosaic spot was nearly equal (RBE = 1.2) to that of 137 Cs γ-rays. The RBE of carbon ions for inducing wing-hair mosaic spots increased as an increase in LET values. The RBE for the induction of eye-color mutants did not change with LET. These relationships suggest that more complex types of DNA damages such as non-rejoinable strand break or clustered double strand break, which increase with LET may be responsible for the induction of wing-hair mutation, while simpler forms of molecular damage may induce a reversion in the white-ivory allele. (M.N.)

Radiosensitization by inhibiting survivin in human hepatoma HepG2 cells to high-LET radiation

International Nuclear Information System (INIS)

Jin Xiaodong; Li Qiang; Wu Qingfeng; Li Ping; Gong Li; Hao Jifang; Dai Zhongying; Matsumoto, Yoshitaka; Furusawa, Yoshiya

2011-01-01

In this study, whether survivin plays a direct role in mediating high-linear energy transfer (LET) radiation resistance in human hepatoma cells was investigated. Small interfering RNA (siRNA) targeting survivin mRNA was designed and transfected into human hepatoma HepG2 cells. Real-time polymerase chain reaction (PCR) and western blotting analyses revealed that survivin expression in HepG2 cells decreased at both transcriptional and post-transcriptional levels after treatment with survivin-specific siRNA. Caspase-3 activity was determined with a microplate reader assay as well. Following exposure to high-LET carbon ions, a reduced clonogenic survival effect, increased apoptotic rates and caspase-3 activity were observed in the cells treated with the siRNA compared to those untreated with the siRNA. The cells with transfection of the survivin-specific siRNA also increased the level of G 2 /M arrest. These results suggest that survivin definitely plays a role in mediating the resistance of HepG2 cells to high-LET radiation and depressing survivin expression might be useful to improve the therapeutic efficacy of heavy ions for radioresistant solid tumors. (author)

Track structure and dose: Alternative conceptual bases for nuclear therapy

International Nuclear Information System (INIS)

Katz, R.

1987-01-01

As one departs from the island of radiation quality encompassing photons and electrons of initial energy from about 100 keV to about 10 MeV toward increasingly higher LET particle irradiations, and from relatively uniform to inherently non-uniform radiation fields, dose and LET become less useful indices of radiation effect. Isodose profiles are not isoeffect profiles. RBEs vary with end point, with the state of oxygenation, with cell line, with tissue identity and with dose, and are multiple valued functions of LET. Dose, microdose and LET lack the descrimination needed to predict biological end points. RBE calculations made from cellular radiosensitivity parameters are consistent with RBEs measured both in vitro and in vivo. For such calculations, we must know the spectrum of particles and particle energies making up a high LET radiation field. To sharpen the calculations and make them directly relevant to therapy, we need to evaluate radiosensitivity parameters for human tissues. Both physical and biological data are needed for radiobiology and radiotherapy. For the question of hazard evaluation, we need to know the relation between transformations in vitro and cancer production in vivo. Using the same model as was used earlier for cellular inactivations, we have fitted tentative radiosensitivity parameters to recent data for cell transformations. The model is consistent with both gamma ray and fission neutron measurements. But a wider range of irradiations is needed to test these results. Delta rays play an important role in heavy ion radiobiology, but we do not now know either the cross-sections for delta ray production or the radial deposition of their energy with sufficient precision or generality. But it is this, the radial dose deposition, which is the physical basis for the calculation of action cross-sections. Studies for radiobiology and radiotherapy should also include the response of different physical detectors to a range of radiations, especially

Airborne and total gamma absorbed dose rates at Patiala - India

International Nuclear Information System (INIS)

Tesfaye, Tilahun; Sahota, H.S.; Singh, K.

1999-01-01

The external gamma absorbed dose rate due to gamma rays originating from gamma emitting aerosols in air, is compared with the total external gamma absorbed dose rate at the Physics Department of Punjabi University, Patiala. It has been found out that the contribution, to the total external gamma absorbed dose rate, of radionuclides on particulate matter suspended in air is about 20% of the overall gamma absorbed dose rate. (author)

Urinary excretion of total isothiocyanates from cruciferous vegetables shows high dose-response relationship and may be a useful biomarker for isothiocyanate exposure

DEFF Research Database (Denmark)

Kristensen, Mette; Krogholm, Kirstine Suszkiewicz; Frederiksen, Hanne

2007-01-01

in urine was quanti- fied as the cyclocondensation product of 1,2-bezenedithiol by high performance liquid chromatography. Results The total urinary excretion of ITCs correlated significantly with the two doses of ITC from diets with high or low cruciferous content (r(s) = 0.90, P

Doses to the red bone marrow of young people and adults from radiation of natural origin

International Nuclear Information System (INIS)

Kendall, G M; Fell, T P

2011-01-01

Natural radiation sources comprise cosmic rays, terrestrial gamma rays, radionuclides in food and inhaled isotopes of radon with their decay products. These deliver doses to all organs and tissues including red bone marrow (RBM), the tissue in which leukaemia is thought to originate. In this paper we calculate the age-dependent annual RBM doses from natural radiation sources to young people and to adults at average levels of exposure in the UK. The contributions to dose are generally less complex than in the case of doses to foetuses and young children where it is necessary to take into account transfer of radionuclides across the placenta, intakes in mother's milk and changes in gut uptake in young infants. However, there is high uptake of alkaline earths and of similar elements in the developing skeleton and this significantly affects the doses from radioisotopes of these elements, not just in the teens and twenties but through into the fifth decade of life. The total equivalent dose to the RBM from all natural sources of radiation at age 15 years is calculated to be about 1200 μSv a year at average UK levels, falling to rather less than 1100 μSv per year in later life; the gentle fall from the late teens onwards reflects the diminishing effect of the high uptakes of radioisotopes of the alkaline earths and of lead in this period. About 60% of the equivalent dose is contributed by the low linear energy transfer (LET) component. Radionuclides in food make the largest contribution to equivalent doses to RBM and much the largest contribution to the absorbed dose from high LET radiation (mainly alpha particles).

Doses to the red bone marrow of young people and adults from radiation of natural origin

Energy Technology Data Exchange (ETDEWEB)

Kendall, G M [Childhood Cancer Research Group, University of Oxford, Richards Building, Old Road Campus, Headington, Oxford OX3 7LG (United Kingdom); Fell, T P, E-mail: Gerald.Kendall@ccrg.ox.ac.uk [Health Protection Agency, CRCE, Chilton, Didcot OX11 0RQ, Oxon (United Kingdom)

2011-09-01

Natural radiation sources comprise cosmic rays, terrestrial gamma rays, radionuclides in food and inhaled isotopes of radon with their decay products. These deliver doses to all organs and tissues including red bone marrow (RBM), the tissue in which leukaemia is thought to originate. In this paper we calculate the age-dependent annual RBM doses from natural radiation sources to young people and to adults at average levels of exposure in the UK. The contributions to dose are generally less complex than in the case of doses to foetuses and young children where it is necessary to take into account transfer of radionuclides across the placenta, intakes in mother's milk and changes in gut uptake in young infants. However, there is high uptake of alkaline earths and of similar elements in the developing skeleton and this significantly affects the doses from radioisotopes of these elements, not just in the teens and twenties but through into the fifth decade of life. The total equivalent dose to the RBM from all natural sources of radiation at age 15 years is calculated to be about 1200 {mu}Sv a year at average UK levels, falling to rather less than 1100 {mu}Sv per year in later life; the gentle fall from the late teens onwards reflects the diminishing effect of the high uptakes of radioisotopes of the alkaline earths and of lead in this period. About 60% of the equivalent dose is contributed by the low linear energy transfer (LET) component. Radionuclides in food make the largest contribution to equivalent doses to RBM and much the largest contribution to the absorbed dose from high LET radiation (mainly alpha particles).

Some cosmic radiation dose measurements aboard flights connecting Zagreb Airport

International Nuclear Information System (INIS)

Vukovic, B.; Radolic, V.; Lisjak, I.; Vekic, B.; Poje, M.; Planinic, J.

2008-01-01

When primary particles from space, mainly protons, enter the atmosphere, they produce interactions with air nuclei, and cosmic-ray showers are induced. The radiation field at aircraft altitude is complex, with different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard A320 and ATR40 aircraft was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter; the neutron dose was measured with the neutron dosimeter consisted of LR-115 track detector and boron foil BN-1 or 10 B converter. The estimated occupational effective dose for the aircraft crew (A320) working 500 h per year was 1.64 mSv. Another experiment was performed at the flights Zagreb-Paris-Buenos Aires and reversely, when one measured non-neutron cosmic radiation dose; for 26.7 h of flight, the MINI 6100 dosimeter gave an average dose rate of 2.3 μSv/h and the TLD dosimeter registered the dose equivalent of 75 μSv or the average dose rate of 2.7 μSv/h; the neutron dosimeter gave the dose rate of 2.4 μSv/h. In the same month, February 2005, a traveling to Japan (24-h-flight: Zagreb-Frankfurt-Tokyo and reversely) and the TLD-100 measurement showed the average dose rate of 2.4 μSv/h; the neutron dosimeter gave the dose rate of 2.5 μSv/h. Comparing dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level, we could conclude that the neutron component carried about 50% of the total dose, that was near other known data

Some cosmic radiation dose measurements aboard flights connecting Zagreb Airport

Energy Technology Data Exchange (ETDEWEB)

Vukovic, B.; Radolic, V. [Department of Physics, University of Osijek, Osijek, P.O. Box 125 (Croatia); Lisjak, I. [Croatia Airlines, Zagreb (Croatia); Vekic, B. [Rudjer Boskovic Institute, Zagreb (Croatia); Poje, M. [Department of Physics, University of Osijek, Osijek, P.O. Box 125 (Croatia); Planinic, J. [Department of Physics, University of Osijek, Osijek, P.O. Box 125 (Croatia)], E-mail: planinic@ffos.hr

2008-02-15

When primary particles from space, mainly protons, enter the atmosphere, they produce interactions with air nuclei, and cosmic-ray showers are induced. The radiation field at aircraft altitude is complex, with different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard A320 and ATR40 aircraft was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter; the neutron dose was measured with the neutron dosimeter consisted of LR-115 track detector and boron foil BN-1 or {sup 10}B converter. The estimated occupational effective dose for the aircraft crew (A320) working 500 h per year was 1.64 mSv. Another experiment was performed at the flights Zagreb-Paris-Buenos Aires and reversely, when one measured non-neutron cosmic radiation dose; for 26.7 h of flight, the MINI 6100 dosimeter gave an average dose rate of 2.3 {mu}Sv/h and the TLD dosimeter registered the dose equivalent of 75 {mu}Sv or the average dose rate of 2.7 {mu}Sv/h; the neutron dosimeter gave the dose rate of 2.4 {mu}Sv/h. In the same month, February 2005, a traveling to Japan (24-h-flight: Zagreb-Frankfurt-Tokyo and reversely) and the TLD-100 measurement showed the average dose rate of 2.4 {mu}Sv/h; the neutron dosimeter gave the dose rate of 2.5 {mu}Sv/h. Comparing dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level, we could conclude that the neutron component carried about 50% of the total dose, that was near other known data.

The biological effects of high dose total body irradiation in beagle dogs

International Nuclear Information System (INIS)

Luo Qingliang; Liu Xiaolan; Hao Jing; Xiong Guolin; Dong Bo; Zhao Zhenhu; Xia Zhengbiao; Qiu Liling; Mao Bingzhi

2002-01-01

Objective: To evaluate the biological effects of Beagle dogs irradiated by γ-rays at different doses. Methods: All Beagle dogs were divided into six groups and were subjected respectively to total-body irradiation (TBI) with a single dose of 6.5, 5.5, 5.0, 4.5, 3, 5 and 2.5 Gy γ-rays delivered by 60 Co sources at 7.224 x 10 -2 C/kg per minute. The general condition, blood cell counts and bone marrow cell CFC assays were observed. Results: Vomiting occurred at 0.5 to 2 hours after TBI in all groups. In 6.5 Gy group 3/5 dogs had blood-watery stool and 1/5 in 5.5 Gy group had watery stool. Diarrhea occurred in all other animals. Only one dog in 2.5 Gy group survived, all of others died. in order of decreasing irradiation dosage, the average survival time was 5.0, 8.0, 9.3, 9.5, 10.5 and 14.1 days, respectively. Conclusions: According to the clinical symptoms, leukocyte count and survival time of the dogs, the irradiation dose which will induce very severe hematopoietic radiation syndrome in Beagle dogs is 4.5 to 5.0 Gy

Tissue responses to low protracted doses of high let radiations or photons: Early and late damage relevant to radio-protective countermeasures

International Nuclear Information System (INIS)

Ainsworth, E.J.; Afzal, S.M.J.; Crouse, D.A.; Hanson, W.R.; Fry, R.J.M.

1988-01-01

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for γ-radiation. When total doses of 96 or 247 cGy of neutrons or γ rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and γ-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. 63 refs., 6 figs., 7 tabs

Photon-Fluence-Weighted let for Radiation Fields Subjected to Epidemiological Studies.

Science.gov (United States)

Sasaki, Michiya

2017-08-01

In order to estimate the uncertainty of the radiation risk associated with the photon energy in epidemiological studies, photon-fluence-weighted LET values were quantified for photon radiation fields with the target organs and irradiation conditions taken into consideration. The photon fluences giving a unit absorbed dose to the target organ were estimated by using photon energy spectra together with the dose conversion coefficients given in ICRP Publication 116 for the target organs of the colon, bone marrow, stomach, lung, skin and breast with three irradiation geometries. As a result, it was demonstrated that the weighted LET values did not show a clear difference among the photon radiation fields subjected to epidemiological studies, regardless of the target organ and the irradiation geometry.

Effects of low doses

International Nuclear Information System (INIS)

Le Guen, B.

2001-01-01

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

What can we learn from the neutron clinical experience for improving ion-beam techniques and high-LET patient selection?

International Nuclear Information System (INIS)

Wambersie, A.; Jones, D.T.L.; Gueulette, J.; Gahbauer, R.; DeLuca, P.M.

2010-01-01

Historically, improvements in radiotherapy have been mainly due to improvements in physical selectivity: beam penetration, collimation, dosimetry, treatment planning; and advances in imaging. Neutrons were the first high-LET (linear energy transfer) radiation to be used clinically and showed improvement in the differential response of radiation resistant tumors and normal tissues. The benefits of fast neutrons (and other forms of high LET radiations) are due to their biological effects: a reduction of the OER, a reduction in the differential cell radiosensitivity related to their position in the mitotic cycle, and a reduction in cellular repair capacity (thus less importance of fractionation). The poor physical selectivity of the early neutron therapy beams introduced a systematic bias in comparison with the photon treatments and created a negative perception for neutron therapy. However, significant improvements in the neutron therapy equipment resulted in a physical selectivity similar to modern MV photon therapy. The tumor types or sites where the best therapeutic results were obtained included inoperable or recurrent salivary gland tumors locally extended prostatic adenocarcinomas, and slowly growing well-differentiated sarcomas. The benefit of neutrons for some other well-defined groups of patients was demonstrated in randomized trials. It was estimated that about 20 % of all radiotherapy patients could benefit from fast neutrons (if neutrons are delivered under satisfactory physical conditions). An important issue for fast neutron therapy is the selection of the types of patients who could most benefit from high-LET radiations. The same issue is raised today with other high-LET radiations (e.g., 12 C ions). It is reasonable to assume that the same types of patients would benefit from 12 C irradiation. Of course the better physical selectivity of ion beams enhances the treatment possibilities but this is true for both the high-LET and low-LET radiations (i

Relative Biological Effectiveness of HZE Fe Ions for Induction ofMicro-Nuclei at Low Doses

Energy Technology Data Exchange (ETDEWEB)

Groesser, Torsten; Chun, Eugene; Rydberg, Bjorn

2007-01-16

Dose-response curves for induction of micro-nuclei (MN) was measured in Chinese hamster V79 and xrs6 (Ku80-) cells and in human mammary epithelial MCF10A cells in the dose range of 0.05-1 Gy. The Chinese Hamster cells were exposed to 1 GeV/u Fe ions, 600 MeV/u Fe ions, and 300 MeV/u Fe ions (LETs of 151, 176 and 235 keV/{micro}m respectively) as well as with 320 kVp X-rays as reference. Second-order polynomials were fitted to the induction curves and the initial slopes (the alpha values) were used to calculate RBE. For the repair proficient V79 cells the RBE at these low doses increased with LET. The values obtained were 3.1 (LET=151 keV/{micro}m), 4.3 (LET = 176 keV/{micro}m) and 5.7 (LET = 235 keV/{micro}m), while the RBE was close to 1 for the repair deficient xrs6 cells regardless of LET. For the MCF10A cells the RBE was determined for 1 GeV/u Fe ions and found to be 5.4, slightly higher than for V79 cells. To test the effect of shielding, the 1 GeV/u Fe ion beam was intercepted by various thickness of high-density polyethylene plastic absorbers, which resulted in energy loss and fragmentation. It was found that the MN yield for V79 cells placed behind the absorbers decreased in proportion to the decrease in dose both before and after the Fe ion Bragg peak (excluding the area around the Fe-ion Bragg peak itself), indicating that RBE did not change significantly due to shielding. At the Bragg peak the effectiveness for MN formation per unit dose was decreased, indicating an 'overkill' effect by low-energy very high-LET Fe ions.

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

Energy Technology Data Exchange (ETDEWEB)

Wang Jufang, E-mail: jufangwang@impcas.ac.c [Institute of Modern Physics, Chinese Academy of Sciences, Nanchang Road No. 509, Lanzhou 730000 (China); Lu Dong; Wu Xin; Sun Haining; Ma Shuang; Li Renmin; Li Wenjian [Institute of Modern Physics, Chinese Academy of Sciences, Nanchang Road No. 509, Lanzhou 730000 (China)

2010-09-15

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV {mu}m{sup -1}) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV {mu}m{sup -1}. The mutation cross section saturated when LET was higher than 58.2 keV {mu}m{sup -1}. Meanwhile, the highest RBE{sub i} for inactivation located at 120.0 keV {mu}m{sup -1} and the highest RBE{sub m} for mutation was at 58.2 keV {mu}m{sup -1}. The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

Life shortening, tumor induction, and tissue dose for fission-neutron and gamma-ray irradiations

International Nuclear Information System (INIS)

Grahn, D.; Duggal, K.; Lombard, L.S.

1985-01-01

The primary focus of this program is to obtain information on the late effects of whole body exposure to low doses of a high linear-energy-transfer (LET) and a low-LET ionizing radiation in experimental animals to provide guidance for the prediction of radiation hazards to man. The information obtained takes the form of dose-response curves for life shortening and for the induction of numerous specific types of tumors. The animals are irradiated with fission neutrons from the Janus reactor and with 60 Co gamma rays, delivered as single, weekly, or duration-of-life exposures covering the range of doses and dose rates. 6 refs

A reviewed technique for total body electron therapy using a Varian Clinac 2100C/D high dose rate treatment beam facility

International Nuclear Information System (INIS)

Oliver, L.D.; Xuereb, E.M.A.; Last, V.; Hunt, P.B.; Wilfert, A.

1996-01-01

Our (Royal North Shore Hospital) most recent linear accelerator acquisition is a Varian Clinac 2100C/D which has a high dose rate (approximately 25Gy per minute at 1 metre) total body electron option. We investigated the physical characteristics of the electron beam to develop a suitable method of treatment for total body electron therapy. The useful electron beam width is defined as 80cm above and below the reference height. Measurements of the electron dose received from the two angled electron beams showed a critical dependence on the gantry angles. The treatment protocol uses ten different patient angles, fractionated into directly opposing fields and treated seuqentially each day. A full cycle of treatment is completed in five days. (author)

Dosimetry and microdosimetry using LET spectrometer based on the track-etch detector: radiotherapy Bremsstrahlung beam, onboard aircraft radiation field

International Nuclear Information System (INIS)

Jadrnickova, I.; Spurny, F.

2006-01-01

The spectrometer of linear energy transfer (Let) based on the chemically etched poly-allyl-diglycol-carbonate (P.A.D.C.) track-etch detector was developed several years ago in our institute. This Let spectrometer enables determining Let of particles approximately from 10 to 700 keV/μm. From the Let spectra, dose characteristics can be calculated. The contribution presents the Let spectra and other dosimetric characteristics obtained onboard a commercial aircraft during more than 6 months long exposure and in the 18 MV radiotherapy Bremsstrahlung beam. (authors)

Low dose epidemiologic studies

International Nuclear Information System (INIS)

Anon.

1990-01-01

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

Liquid ionization chambers for LET determination

DEFF Research Database (Denmark)

Kaiser, Franz-Joachim; Bassler, Niels; Tölli, Heikki

Liquid ionization chambers [1] (LICs) have have been used in the last decades as background dosemeters. Since a few years LICs are also commercially available for dosimetry and are used for measurements of dose distributions where a high spatial distribution is necessary. Also in the last decades...... a differential equation applying several simplifications and approximations leading to discrepancies between theory and experiments [3]. The theory predicts the collection efficiency as a function of the electrical field and was applied for both air filled ionization chambers and liquid filled ionization...... chambers. For liquids the LET can be roughly deduced from the collection efficiency dependency on the electrical field inside a liquid ionization chambers [4] using an extrapolation method. We solved the fundamental differential equation again presented by Jaffe numerically, but now taking into account...

Ataxia telangiectasia: LET dependence of cellular inactivation

International Nuclear Information System (INIS)

Blakely, E.A.; Tobias, C.A.

1984-01-01

Human Ataxia telangiectasia cells (AT 2SF line) have been irradiated in vitro under aerobic and hypoxic conditions with heavy-ion beams accelerated at the Berkeley Bevalac as a part of a study to characterize the radiation responses of genetically sensitive and resistant cell lines to high LET radiations. Results from track-segment exposures to neon, silicon, argon and iron ion beams accelerated to initial energies of from 225 to 670 MeV/amu provided an LET range between 30 to 1,000 KeV/μm. The data indicate: (1) The sensitivity of AT cells increases with increasing LET, similar to resistant human lines (e.g., T-1 cells). However, due to efficient repair, T-1 cells are more resistant than AT cells at LET values below 200 keV/μm; (2) Maximum cell kill occurs for both lines at 100-200 keV/μm; at higher LET the sensitivity of the two lines approach each other; (3) There is only small variation in the sensitivity of AT cells to particles of various atomic numbers at the same LET; differences are more pronounced in the LET domain between 50 and 200 keV/μm; and (4) AT cells have slightly lower OER values than T-1 cells in the range of LET studied below 200 keV/μm

Time- and dose-dependent effects of total-body ionizing radiation on muscle stem cells

Science.gov (United States)

Masuda, Shinya; Hisamatsu, Tsubasa; Seko, Daiki; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng; Ono, Yusuke

2015-01-01

Exposure to high levels of genotoxic stress, such as high-dose ionizing radiation, increases both cancer and noncancer risks. However, it remains debatable whether low-dose ionizing radiation reduces cellular function, or rather induces hormetic health benefits. Here, we investigated the effects of total-body γ-ray radiation on muscle stem cells, called satellite cells. Adult C57BL/6 mice were exposed to γ-radiation at low- to high-dose rates (low, 2 or 10 mGy/day; moderate, 50 mGy/day; high, 250 mGy/day) for 30 days. No hormetic responses in proliferation, differentiation, or self-renewal of satellite cells were observed in low-dose radiation-exposed mice at the acute phase. However, at the chronic phase, population expansion of satellite cell-derived progeny was slightly decreased in mice exposed to low-dose radiation. Taken together, low-dose ionizing irradiation may suppress satellite cell function, rather than induce hormetic health benefits, in skeletal muscle in adult mice. PMID:25869487

Total dose and dose rate models for bipolar transistors in circuit simulation.

Energy Technology Data Exchange (ETDEWEB)

Campbell, Phillip Montgomery; Wix, Steven D.

2013-05-01

The objective of this work is to develop a model for total dose effects in bipolar junction transistors for use in circuit simulation. The components of the model are an electrical model of device performance that includes the effects of trapped charge on device behavior, and a model that calculates the trapped charge densities in a specific device structure as a function of radiation dose and dose rate. Simulations based on this model are found to agree well with measurements on a number of devices for which data are available.

Clinical study on the adriamycin induced cardiomyopathy using the cardiac magnetic resonance imaging. Total dose and cardiac dysfunction

International Nuclear Information System (INIS)

Yamaguchi, Kyoko; Teraoka, Kunihiko; Hirano, Masaharu

2001-01-01

We studied cardiac functional disorders caused by Adoriamycin using gadolinium (Gd) contrast cine MRI. Forty-eight patients were given ACT (31 men and 17 women; mean age, 52±15 years). First, the relationship between dose and the left ventricular volume, cardiac function, left ventricular cardiac mass and localized wall motion were examined in all patients. Patients given a total dose of 300 mg/m 2 or higher were assigned to the high dose group and those given doses under 300 mg/m 2 to the low dose group. The same parameters were studied in both groups and compared. A 1.5-Tesla superconductive MRI was used for all studies. Cine images of the long and short axes at the papillary muscle level were obtained by ECG R-wave synchronized Gd contrast cine MRI. Left ventricular volume and cardiac function were analyzed using the long-axis cine images and the wall thickness in diastole and systole was measured at each site using the short-axis cine images. The percentage of wall thickness was calculated at each site. The mean ACT dose was 273.3±218.2 mg/m 2 . In all patients the total dose directly correlated with ESVI and inversely correlated with the ejection fraction (EF). In the high dose group, the total dose and EF were inversely correlated, but no significant differences were observed in the low dose group. In the high dose group, the ESVI was significantly greater and the SVI and EF were more significantly reduced than in the low dose group. In the high dose group, the thickness of the anterior, lateral and posterior walls, excluding the septum, was significantly lower than in the low dose group. However, changes in wall thickness were not significantly different between the groups. Gd contrast cine MRI was useful in examining cardiac functional disorders caused by anthracyclines. The total dose of anthracycline correlated directly with the ESVI, and inversely with the EF. A total dose of 300 mg/m 2 appeared to be the borderline dose beyond which there were

Clinical study on the adriamycin induced cardiomyopathy using the cardiac magnetic resonance imaging. Total dose and cardiac dysfunction

Energy Technology Data Exchange (ETDEWEB)

Yamaguchi, Kyoko; Teraoka, Kunihiko; Hirano, Masaharu [Tokyo Medical Coll. (Japan)

2001-05-01

We studied cardiac functional disorders caused by Adoriamycin using gadolinium (Gd) contrast cine MRI. Forty-eight patients were given ACT (31 men and 17 women; mean age, 52{+-}15 years). First, the relationship between dose and the left ventricular volume, cardiac function, left ventricular cardiac mass and localized wall motion were examined in all patients. Patients given a total dose of 300 mg/m{sup 2} or higher were assigned to the high dose group and those given doses under 300 mg/m{sup 2} to the low dose group. The same parameters were studied in both groups and compared. A 1.5-Tesla superconductive MRI was used for all studies. Cine images of the long and short axes at the papillary muscle level were obtained by ECG R-wave synchronized Gd contrast cine MRI. Left ventricular volume and cardiac function were analyzed using the long-axis cine images and the wall thickness in diastole and systole was measured at each site using the short-axis cine images. The percentage of wall thickness was calculated at each site. The mean ACT dose was 273.3{+-}218.2 mg/m{sup 2}. In all patients the total dose directly correlated with ESVI and inversely correlated with the ejection fraction (EF). In the high dose group, the total dose and EF were inversely correlated, but no significant differences were observed in the low dose group. In the high dose group, the ESVI was significantly greater and the SVI and EF were more significantly reduced than in the low dose group. In the high dose group, the thickness of the anterior, lateral and posterior walls, excluding the septum, was significantly lower than in the low dose group. However, changes in wall thickness were not significantly different between the groups. Gd contrast cine MRI was useful in examining cardiac functional disorders caused by anthracyclines. The total dose of anthracycline correlated directly with the ESVI, and inversely with the EF. A total dose of 300 mg/m{sup 2} appeared to be the borderline dose beyond

Impact of radiation technique, radiation fraction dose, and total cisplatin dose on hearing. Retrospective analysis of 29 medulloblastoma patients

International Nuclear Information System (INIS)

Scobioala, Sergiu; Kittel, Christopher; Ebrahimi, Fatemeh; Wolters, Heidi; Eich, Hans Theodor; Parfitt, Ross; Matulat, Peter; Am Zehnhoff-Dinnesen, Antoinette

2017-01-01

To analyze the incidence and degree of sensorineural hearing loss (SNHL) resulting from different radiation techniques, fractionation dose, mean cochlear radiation dose (D mean ), and total cisplatin dose. In all, 29 children with medulloblastoma (58 ears) with subclinical pretreatment hearing thresholds participated. Radiotherapy (RT) and cisplatin had been applied sequentially according to the HIT MED Guidance. Audiological outcomes up to the latest follow-up (median 2.6 years) were compared. Bilateral high-frequency SNHL was observed in 26 patients (90%). No significant differences were found in mean hearing threshold between left and right ears at any frequency. A significantly better audiological outcome (p < 0.05) was found after tomotherapy at the 6 kHz bone-conduction threshold (BCT) and left-sided 8 kHz air-conduction threshold (ACT) than after a combined radiotherapy technique (CT). Fraction dose was not found to have any impact on the incidence, degree, and time-to-onset of SNHL. Patients treated with CT had a greater risk of SNHL at high frequencies than tomotherapy patients even though D mean was similar. Increase in severity of SNHL was seen when the total cisplatin dose reached above 210 mg/m 2 , with the highest abnormal level found 8-12 months after RT regardless of radiation technique or fraction dose. The cochlear radiation dose should be kept as low as possible in patients who receive simultaneous cisplatin-based chemotherapy. The risk of clinically relevant HL was shown when D mean exceeds 45 Gy independent of radiation technique or radiation regime. Cisplatin ototoxicity was shown to have a dose-dependent effect on bilateral SNHL, which was more pronounced in higher frequencies. (orig.) [de

Application of the high-temperature ratio method for evaluation of the depth distribution of dose equivalent in a water-filled phantom on board space station Mir

International Nuclear Information System (INIS)

Berger, T.; Hajek, M.; Schoener, W.; Fugger, M.; Vana, N.; Akatov, Y.; Shurshakov, V.; Arkhangelsky, V.; Kartashov, D.

2002-01-01

A water-filled tissue equivalent phantom with a diameter of 35 cm was developed at the Institute for Biomedical Problems, Moscow, Russia. It contains four channels perpendicular to each other, where dosemeters can be exposed at different depths. Between May 1997 and February 1999 the phantom was installed at three different locations on board the Mir space station. Thermoluminescence dosemeters (TLDs) were exposed at various depths inside the phantom either parallel or perpendicular to the hull of the spacecraft. The high-temperature ratio (HTR) method was used for the evaluation of the TLDs. The method was developed at the Atominstitute of the Austrian Universities, Vienna, Austria, and has already been used for measurements in mixed radiation fields on earth and in space with great success. It uses the changes of peak height ratios in LiF:Mg,Ti glow curves in dependence on the linear energy transfer (LET), and therefore allows determination of an 'averaged' LET as well as measurement of the absorbed dose. A mean quality factor and, subsequently, the dose equivalent can be calculated according to the Q(LET ( ) relationship proposed by the ICRP. The small size of the LiF dosemeters means that the HTR method can be used to determine the gradient of absorbed dose and dose equivalent inside the tissue equivalent body. (author)

The carcinogenic risks of low-LET and high-LET ionizing radiations

International Nuclear Information System (INIS)

Fabrikant, J.I.

1991-08-01

This report presents a discussion on risk from ionizing radiations to human populations. Important new information on human beings has come mainly from further follow-up of existing epidemiological studies, notably the Japanese atomic bomb survivors and the ankylosing spondylitis patients; from new epidemiological surveys, such as the patients treated for cancer of the uterine cervix; and from combined surveys, including workers exposed in underground mines. Since the numerous and complex differences among the different study populations introduce factors that influence the risk estimates derived in ways that are not completely understood, it is not clear how to combine the different risk estimates obtained. These factors involve complex biological and physical variables distributed over time. Because such carcinogenic effects occur too infrequently to be demonstrated at low doses, the risks of low-dose radiation can be estimated only by interpolation from observations at high doses on the basis of theoretical concepts, mathematical models and available empirical evidence, primarily the epidemiological surveys of large populations exposed to ionizing radiation. In spite of a considerable amount of research, only recently has there has been efforts to apply the extensive laboratory data in animals to define the dose-incidence relationship in the low dose region. There simply are insufficient data in the epidemiological studies of large human populations to estimate risk coefficients directly from exposure to low doses. The risk estimates for the carcinogenic effects of radiation have been, in the past, somewhat low and reassessment of the numerical values is now necessary

A saturable repair model for radionuclide therapy using low LET radiation emitters

International Nuclear Information System (INIS)

Calderon, Carlos F.; Joaquin Gonzalez; Guido Martin

2004-01-01

Purpose: In conventional radiotherapy doses of about 60Gy are necessary to achieve the tumor control or eradication. For systemic applications in radionuclide radiotherapy (RT) 0.1-0.5cGy/min and total dose 15-20 Gy could be reached with effective irradiation times of few days. The dose rate in tumor change exponentially as a time function where an uptake phase well differentiated from an elimination phase-will- appear both determined by the effective uptake and elimination times respectively. The biological response in RT will be determined not only by the total dose, but also by initial dose rate, the length of irradiation time (effective half-life) and biological factors, like radiosensitivity, repair and doubling times. Most quantitative models of radiation action on cells make the assumption that cell repair mechanisms are relevant in the response and it proceed in a dose-dependent way. The cell proliferation will influence too the response when the overall irradiation is comparable or greater than cell population doubling time. Many proposal had been made to apply radiobiological model for the prediction of the treatment response in RN. Saturable repair models are able, in principle, to explain the usual data base of radiobiological phenomena including which where other biophysical model does not work good. It is presented here an analytical expression to calculate the survival fraction in a cell population after irradiation based on a saturable repair radiobiological model proposed by Sanchez-Reyes [Sanchez-Reyes A. Radiact. Res., 1992;130:139-147] as function of radiobiological and biokinetics parameters which could be used in RN. The original radiobiological model consider a cell population where the DNA repair mechanisms are saturable and it could be affected by radiation action. The contribution of cell proliferation were considered keeping in mind that cell population grow up exponentially at constant rate. The dose rate was considered uniformly

Total dose and dose rate radiation characterization of EPI-CMOS radiation hardened memory and microprocessor devices

International Nuclear Information System (INIS)

Gingerich, B.L.; Hermsen, J.M.; Lee, J.C.; Schroeder, J.E.

1984-01-01

The process, circuit discription, and total dose radiation characteristics are presented for two second generation hardened 4K EPI-CMOS RAMs and a first generation 80C85 microprocessor. Total dose radiation performance is presented to 10M rad-Si and effects of biasing and operating conditions are discussed. The dose rate sensitivity of the 4K RAMs is also presented along with single event upset (SEU) test data

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

Energy Technology Data Exchange (ETDEWEB)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States)

2013-05-15

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

International Nuclear Information System (INIS)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

2013-01-01

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

Science.gov (United States)

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

2013-05-01

Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability

On the correctness of the thermoluminescent high-temperature ratio (HTR) method for estimating ionization density effects in mixed radiation fields

International Nuclear Information System (INIS)

Bilski, Pawel

2010-01-01

The high-temperature ratio (HTR) method which exploits changes in the LiF:Mg,Ti glow-curve due to high-LET radiation, has been used for several years to estimate LET in an unknown radiation field. As TL efficiency is known to decrease after doses of densely ionizing radiation, a LET estimate is used to correct the TLD-measured values of dose. The HTR method is purely empirical and its general correctness is questionable. The validity of the HTR method was investigated by theoretical simulation of various mixed radiation fields. The LET eff values estimated with the HTR method for mixed radiation fields were found in general to be incorrect, in some cases underestimating the true values of dose-averaged LET by an order of magnitude. The method produced correct estimates of average LET only in cases of almost mono-energetic fields (i.e. in non-mixed radiation conditions). The value of LET eff found by the HTR method may therefore be treated as a qualitative indicator of increased LET, but not as a quantitative estimator of average LET. However, HTR-based correction of the TLD-measured dose value (HTR-B method) was found to be quite reliable. In all cases studied, application of this technique improved the result. Most of the measured doses fell within 10% of the true values. A further empirical improvement to the method is proposed. One may therefore recommend the HTR-B method to correct for decreased TL efficiency in mixed high-LET fields.

The hyper-radiosensitivity effect of human hepatoma SMMC-7721 cells exposed to low dose γ-rays and 12C ions

International Nuclear Information System (INIS)

Jin Xiaodong; Li Qiang; Li Wenjian; Wang Jufang; Guo Chuanling; Hao Jifang

2006-01-01

Hypersensitive response of mammalian cells in cell killing to X- and γ-rays has been reported at doses below 1 Gy. The purpose of this study was to examine the low dose sensitivity of human hepatoma SMMC-7721 cells irradiated with 6 Co γ-rays and 50 MeV/u 12 C ions. Experiments using γ-rays and charged particle irradiation were performed, particularly in the low dose range from 0 to 2 Gy. The survival effect of SMMC-7721 cells was measured by means of standard clonogenic assay in conjunction with a cell sorter. The result indicates SMMC-7721 cells showed hyper-radiosensitive response at low doses and increased radio-resistance at larger single doses for the carbon ions (LET = 45.2 keV/μm) and the γ-rays. However, the HRS/IRR effect caused by high-LET irradiation is different from that by low-LET radiation. This might possibly be due to the difference in the mode of energy deposition by particle beam and low-LET irradiation

Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

Energy Technology Data Exchange (ETDEWEB)

Jones, Bleddyn [Gray Laboratory, CRUK/MRC Oxford Oncology Institute, The University of Oxford, ORCRB-Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

2015-03-17

Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated.

Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

International Nuclear Information System (INIS)

Jones, Bleddyn

2015-01-01

Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated

Enhancement of Transistor-to-Transistor Variability Due to Total Dose Effects in 65-nm MOSFETs

CERN Document Server

Gerardin, S; Cornale, D; Ding, L; Mattiazzo, S; Paccagnella, A; Faccio, F; Michelis, S

2015-01-01

We studied device-to-device variations as a function of total dose in MOSFETs, using specially designed test structures and procedures aimed at maximizing matching between transistors. Degradation in nMOSFETs is less severe than in pMOSFETs and does not show any clear increase in sample-to-sample variability due to the exposure. At doses smaller than 1 Mrad( SiO2) variability in pMOSFETs is also practically unaffected, whereas at very high doses-in excess of tens of Mrad( SiO2)-variability in the on-current is enhanced in a way not correlated to pre-rad variability. The phenomenon is likely due to the impact of random dopant fluctuations on total ionizing dose effects.

Fast Neutrons - LET Distributions and the Response of Mammalian Cells

Energy Technology Data Exchange (ETDEWEB)

Bewley, D. K. [Medical Research Council Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)

1968-03-15

Distributions of stopping power (LET) are given for four beams of fast neutrons, namely, neutrons of 14.6 MeV, neutrons produced by bombarding a thick beryllium target with 15 MeV deuterons, neutrons of 3 MeV, and fast neutrons produced by bombardment of a {sup 235}U converter plate with thermal neutrons. The track average LET is correlated with mean neutron energy, but the dose average is approximately constant. However, neither of these types of average is expected to have much relevance to radiobiology. Further, specification of a ''biologically effective LET'' depends on the biological test used, and is not solely a function of the radiation quality. An attempt has been made to calculate the response of T.I. kidney cells in tissue culture to these four beams of neutrons, based on their response to charged particles using the track-segment method. The calculated RBE's of the neutron beams are lower than the observed values and the calculated values of the oxygen enhancement ratio are higher. These differences seem too great to be explained by errors in dosimetry and in the calculated LET spectra. The suggestion is made that LET is not an adequate criterion of radiation quality, and that the discrepancies may be explained by more detailed consideration of the part played by delta rays and by heavy recoil tracks of short range. (author)

p-MOSFET total dose dosimeter

Science.gov (United States)

Buehler, Martin G. (Inventor); Blaes, Brent R. (Inventor)

1994-01-01

A p-MOSFET total dose dosimeter where the gate voltage is proportional to the incident radiation dose. It is configured in an n-WELL of a p-BODY substrate. It is operated in the saturation region which is ensured by connecting the gate to the drain. The n-well is connected to zero bias. Current flow from source to drain, rather than from peripheral leakage, is ensured by configuring the device as an edgeless MOSFET where the source completely surrounds the drain. The drain junction is the only junction not connected to zero bias. The MOSFET is connected as part of the feedback loop of an operational amplifier. The operational amplifier holds the drain current fixed at a level which minimizes temperature dependence and also fixes the drain voltage. The sensitivity to radiation is made maximum by operating the MOSFET in the OFF state during radiation soak.

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

Science.gov (United States)

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

2016-04-01

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

Determination of the total indicative dose in drinking and mineral waters

International Nuclear Information System (INIS)

Flesch, K.; Schulz, H.; Knappik, R.; Koehler, M.

2006-01-01

In Europe and Germany administrative regulations exist for the surveillance of the total indicative dose of water supplied for human consumption. This parameter, which cannot be analyzed directly, has to be calculated using nuclide specific activity concentration and age specific dose conversion factors and consumption rates. Available calculation methods differ regarding the used radionuclides, consumption rates and whether they use age specific dose conversion factors or not. In Germany administrative guidelines for the determination of the total indicative dose are still not available. As they have analyzed a large number of waters in the past, the authors derive a praxis orientated concept for the determination of the total indicative dose which respects radiological, analytical and hydrochemical aspects as well. Finally it is suggested to handle sparkling waters in the same manner as drinking waters. (orig.)

Prevention of cigarette smoke induced lung cancer by low let ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Sanders, Charles L. [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2008-12-15

Lung cancer is the most prevalent global cancer, {approx}90% of which is caused by cigarette smoking. The LNT hypothesis has been inappropriately applied to estimate lung cancer risk due to ionizing radiation. A threshold of {approx}1 Gy for lung cancer has been observed in never smokers. Lung cancer risk among nuclear workers, radiologists and diagnostically exposed patients was typically reduced by {approx}40% following exposure to <100 mSv low LET radiation. The consistency and magnitude of reduced lung cancer in nuclear workers and occurrence of reduced lung cancer in exposed non-worker populations could not be explained by the HWE. Ecologic studies of indoor radon showed highly significant reductions in lung cancer risk. A similar reduction in lung cancer was seen in a recent well designed case-control study of indoor radon, indicating that exposure to radon at the EPA action level is associated with a decrease of {approx}60% in lung cancer. A cumulative whole-body dose of {approx}1 Gy gamma rays is associated with a marked decrease in smoking-induced lung cancer in plutonium workers. Low dose, low LET radiation appears to increase apoptosis mediated removal of {alpha}-particle and cigarette smoke transformed pulmonary cells before they can develop into lung cancer.

Prevention of cigarette smoke induced lung cancer by low let ionizing radiation

International Nuclear Information System (INIS)

Sanders, Charles L.

2008-01-01

Lung cancer is the most prevalent global cancer, ∼90% of which is caused by cigarette smoking. The LNT hypothesis has been inappropriately applied to estimate lung cancer risk due to ionizing radiation. A threshold of ∼1 Gy for lung cancer has been observed in never smokers. Lung cancer risk among nuclear workers, radiologists and diagnostically exposed patients was typically reduced by ∼40% following exposure to <100 mSv low LET radiation. The consistency and magnitude of reduced lung cancer in nuclear workers and occurrence of reduced lung cancer in exposed non-worker populations could not be explained by the HWE. Ecologic studies of indoor radon showed highly significant reductions in lung cancer risk. A similar reduction in lung cancer was seen in a recent well designed case-control study of indoor radon, indicating that exposure to radon at the EPA action level is associated with a decrease of ∼60% in lung cancer. A cumulative whole-body dose of ∼1 Gy gamma rays is associated with a marked decrease in smoking-induced lung cancer in plutonium workers. Low dose, low LET radiation appears to increase apoptosis mediated removal of α-particle and cigarette smoke transformed pulmonary cells before they can develop into lung cancer

Theoretical analysis of the dose dependence of the oxygen enhancement ratio and its relevance for clinical applications

International Nuclear Information System (INIS)

Wenzl, Tatiana; Wilkens, Jan J

2011-01-01

The increased resistance of hypoxic cells to ionizing radiation is usually believed to be the primary reason for treatment failure in tumors with oxygen-deficient areas. This oxygen effect can be expressed quantitatively by the oxygen enhancement ratio (OER). Here we investigate theoretically the dependence of the OER on the applied local dose for different types of ionizing irradiation and discuss its importance for clinical applications in radiotherapy for two scenarios: small dose variations during hypoxia-based dose painting and larger dose changes introduced by altered fractionation schemes. Using the widespread Alper-Howard-Flanders and standard linear-quadratic (LQ) models, OER calculations are performed for T1 human kidney and V79 Chinese hamster cells for various dose levels and various hypoxic oxygen partial pressures (pO2) between 0.01 and 20 mmHg as present in clinical situations in vivo. Our work comprises the analysis for both low linear energy transfer (LET) treatment with photons or protons and high-LET treatment with heavy ions. A detailed analysis of experimental data from the literature with respect to the dose dependence of the oxygen effect is performed, revealing controversial opinions whether the OER increases, decreases or stays constant with dose. The behavior of the OER with dose per fraction depends primarily on the ratios of the LQ parameters alpha and beta under hypoxic and aerobic conditions, which themselves depend on LET, pO2 and the cell or tissue type. According to our calculations, the OER variations with dose in vivo for low-LET treatments are moderate, with changes in the OER up to 11% for dose painting (1 or 3 Gy per fraction compared to 2 Gy) and up to 22% in hyper-/hypofractionation (0.5 or 20 Gy per fraction compared to 2 Gy) for oxygen tensions between 0.2 and 20 mmHg typically measured clinically in hypoxic tumors. For extremely hypoxic cells (0.01 mmHg), the dose dependence of the OER becomes more pronounced (up to 36

Differential effects of p53 on bystander phenotypes induced by gamma ray and high LET heavy ion radiation

Science.gov (United States)

He, Mingyuan; Dong, Chen; Konishi, Teruaki; Tu, Wenzhi; Liu, Weili; Shiomi, Naoko; Kobayashi, Alisa; Uchihori, Yukio; Furusawa, Yoshiya; Hei, Tom K.; Dang, Bingrong; Shao, Chunlin

2014-04-01

High LET particle irradiation has several potential advantages over γ-rays such as p53-independent response. The purpose of this work is to disclose the effect of p53 on the bystander effect induced by different LET irradiations and underlying mechanism. Lymphocyte cells of TK6 (wild type p53) and HMy2.CIR (mutated p53) were exposed to either low or high LET irradiation, then their mitochondrial dysfunction and ROS generation were detected. The micronuclei (MN) induction in HL-7702 hepatocytes co-cultured with irradiated lymphocytes was also measured. It was found that the mitochondrial dysfunction, p66Shc activation, and intracellular ROS were enhanced in TK6 but not in HMy2.CIR cells after γ-ray irradiation, but all of them were increased in both cell lines after carbon and iron irradiation. Consistently, the bystander effect of MN formation in HL-7702 cells was only triggered by γ-irradiated TK6 cells but not by γ-irradiated HMy2.CIR cells. But this bystander effect was induced by both lymphocyte cell lines after heavy ion irradiation. PFT-μ, an inhibitor of p53, only partly inhibited ROS generation and bystander effect induced by 30 keV/μm carbon-irradiated TK6 cells but failed to suppress the bystander effect induced by the TK6 cells irradiated with either 70 keV/μm carbon or 180 keV/μm iron. The mitochondrial inhibitors of rotenone and oligomycin eliminated heavy ion induced ROS generation in TK6 and HMy2.CIR cells and hence diminished the bystander effect on HL-7702 cells. These results clearly demonstrate that the bystander effect is p53-dependent for low LET irradiation, but it is p53-independent for high LET irradiation which may be because of p53-independent ROS generation due to mitochondrial dysfunction.

Air filled ionization chambers and their response to high LET radiation

DEFF Research Database (Denmark)

Kaiser, Franz-Joachim; Bassler, Niels; Tölli, Heikki

Background Air filled ionization chambers (ICs) are widely used for absolute dosimetry, not only in photon beams but also in beams of heavy charged particles. Within the IC, electron hole pairs are generated by the energy deposition originating from incoming radiation. High-LET particles create......-plate ionization chamber exposed to heavy ions Phys. Med. Biol. 43 3549–58, 1998. ELSAESSER, T. et al.: Impact of track structure on biological treatment planning ion ion radiotherapy. New Journal pf Physics 10. 075005, 2008...

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

NARCIS (Netherlands)

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

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

Optimization of total arc degree for stereotactic radiotherapy by using integral biologically effective dose and irradiated volume

International Nuclear Information System (INIS)

Lim, Do Hoon; Kim, Dae Yong; Lee, Myung Za; Chun, Ha Chung

2001-01-01

To find the optimal values of total arc degree to protect the normal brain tissue from high dose radiation in stereotactic radiotherapy planning. With Xknife-3 planning system and 4 MV linear accelerator, the authors planned under various values of parameters. One isocenter, 12, 20, 30, 40, 50, and 60 mm of collimator diameters, 100 deg, 200 deg, 300 deg, 400 deg, 500 deg, 600 deg, of total arc degrees, and 30 deg or 45 deg of arc intervals were used. After the completion of planning, the plans were compared each other using V 50 (the volume of normal brain that is delivered high dose radiation) and integral biologically effective dose. At 30 deg of arc interval, the values of V 50 had the decreased pattern with the increase of total arc degree in any collimator diameter. At 45 deg arc interval, up to 400 deg of total arc degree, the values of V 50 decreased with the increase of total arc degree, but at 500 deg and 600 deg of total arc degrees, the values increased. At 30 deg of arc interval, integral biologically effective dose showed the decreased pattern with the increase of total arc degree in any collimator diameter. At 45 deg arc interval with less than 40 mm collimator diameter, the integral biologically effective dose decreased with the increase of total arc degree, but with 50 and 60 mm of collimator diameters, up to 400 deg of total arc degree, integral biologically effective dose decreased with the increase of total arc degree, but at 500 deg and 600 deg of total arc degrees, the values increased. In the stereotactic radiotherapy planning for brain lesions, planning with 400 deg of total arc degree is optimal. Especially, when the larger collimator more than 50 mm diameter should be used, the uses of 500 deg and 600 deg of total arc degrees make the increase of V 50 and integral biologically effective dose, Therefore stereotactic radiotherapy planning using 400 deg of total arc degree can increase the therapeutic ratio and produce the effective outcome

The Antiproton Depth-Dose Curve in Water

DEFF Research Database (Denmark)

Bassler, Niels; Holzscheiter, Michael; Jäkel, Oliver

2008-01-01

We have measured the depth-dose curve of 126 MeV antiprotons in a water phantom using ionization chambers. Since the antiproton beam provided by CERN has a pulsed structure and possibly carries a high-LET component from the antiproton annihilation, it is necessary to correct the acquired charge...

Total Risk Management for Low Dose Radiation Exposures

International Nuclear Information System (INIS)

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

2012-01-01

health. This view is supported with numerous evidences, and explained with beneficial effects from the increased activity of immune system activated with small radiation exposures. Finally, theory in between is that small doses are less than linearly proportionally harmful and that they are presenting a much smaller risks than according to the LNT. This view is derived from the use of different evidences. Difficulties to find one single theory about effects of small radiation doses are related to existence of huge variability and uncertainty in the evidence data. This is very hard experimental and theoretical problem. It will require lots of additional research to reduce these uncertainties and find final theory. This might be too late for the number of people affected in different ways with current single most conservative LNT approach. The problem with the conservative LNT regulatory approach is resulting in enormous additional costs of nuclear energy and medical applications. Which is reasonable and acceptable during the regular operation when source is high and concentrated. But, this becomes unreasonable huge economic burden after accidents and for cleanups with nuclear facilities. Similar problem arises with restriction of medical examinations and treatments based on over conservative risk estimate. Special circumstances are with evacuated people from contaminated areas where they are on the one side saved from small radiation exposures, and on the other side exposed to years of life away from their home and with numerous direct and indirect additional risks (i.e., stress, social problems, etc.). It seems reasonable that some alternative (total) risk management approach might be much more suitable for this situation. Evacuation of people from contaminated area with small doses sources should not be done when that induces larger risks from even what is expected from radiation based on LNT. Similar total risk management could be also applied for with medical

Clinical implementation of total skin electron irradiation treatment with a 6 MeV electron beam in high-dose total skin electron mode

International Nuclear Information System (INIS)

Lucero, J. F.; Rojas, J. I.

2016-01-01

Total skin electron irradiation (TSEI) is a special treatment technique offered by modern radiation oncology facilities, given for the treatment of mycosis fungoides, a rare skin disease, which is type of cutaneous T-cell lymphoma [1]. During treatment the patient’s entire skin is irradiated with a uniform dose. The aim of this work is to present implementation of total skin electron irradiation treatment using IAEA TRS-398 code of practice for absolute dosimetry and taking advantage of the use of radiochromic films.

Clinical implementation of total skin electron irradiation treatment with a 6 MeV electron beam in high-dose total skin electron mode

Energy Technology Data Exchange (ETDEWEB)

Lucero, J. F., E-mail: fernando.lucero@hoperadiotherapy.com.gt [Universidad Nacional de Costa Rica, Heredia (Costa Rica); Hope International, Guatemala (Guatemala); Rojas, J. I., E-mail: isaac.rojas@siglo21.cr [Centro Médico Radioterapia Siglo XXI, San José (Costa Rica)

2016-07-07

Total skin electron irradiation (TSEI) is a special treatment technique offered by modern radiation oncology facilities, given for the treatment of mycosis fungoides, a rare skin disease, which is type of cutaneous T-cell lymphoma [1]. During treatment the patient’s entire skin is irradiated with a uniform dose. The aim of this work is to present implementation of total skin electron irradiation treatment using IAEA TRS-398 code of practice for absolute dosimetry and taking advantage of the use of radiochromic films.

miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition.

Science.gov (United States)

Song, Juhyun; Yoon, So Ra; Kim, Oh Yoen

2017-01-01

Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor- α ), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.

Pulsed total dose damage effect experimental study on EPROM

International Nuclear Information System (INIS)

Luo Yinhong; Yao Zhibin; Zhang Fengqi; Guo Hongxia; Zhang Keying; Wang Yuanming; He Baoping

2011-01-01

Nowadays, memory radiation effect study mainly focus on functionality measurement. Measurable parameters is few in china. According to the present situation, threshold voltage testing method was presented on floating gate EPROM memory. Experimental study of pulsed total dose effect on EPROM threshold voltage was carried out. Damage mechanism was analysed The experiment results showed that memory cell threshold voltage negative shift was caused by pulsed total dose, memory cell threshold voltage shift is basically coincident under steady bias supply and no bias supply. (authors)

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

International Nuclear Information System (INIS)

Johnston, Peter J.; Wilson, George D.

2003-01-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Dose rate and total dose dependence of the 1/f noise performance of a GaAs operational amplifier during irradiation

International Nuclear Information System (INIS)

Hiemstra, D.M.

1995-01-01

A pictorial of a sectioned view of the torus of the International Thermonuclear Experimental Reactor (ITER) is shown. Maintenance and inspection of the reactor are required to be performed remotely. This is due to the high gamma radiation environment in vessel during inspection and maintenance activities. The custom GaAs operational amplifier is to be used to readout sensors on the in-vessel manipulator and inspection equipment. The gamma dose rate during maintenance and inspection is anticipated to be 3 Mrad(GaAs)/hour. Here, dose rate and total dose dependence of the 1/f noise performance of a custom GaAs MESFET operational amplifier during irradiation are presented. Dose rate dependent 1/f noise degradation during irradiation is believed to be due to electron trapping in deep levels, enhanced by backgating and shallow traps excited during irradiation. The reduction of this affect with accumulated total dose is believed to be due a reduction of deep level site concentration associated with substitutional oxygen. Post irradiation 1/f noise degradation is also presented.The generation-recombination noise observed post irradiation can be attributed to the production of shallow traps due to ionizing radiation

Physiological and immunological changes following exposure to low versus high-dose ionizing irradiation; comparative analysis with dose rate and cumulative dose

International Nuclear Information System (INIS)

Heesun, Kim; Heewon, Jang; Soungyeon, Song; Shinhye, Oh; Cukcheul, Shin; Meeseon, Jeong; Chasoon, Kim; Kwnaghee, Yang; Seonyoung, Nam; Jiyoung, Kim; Youngwoo, Jin; Changyoung, Cha

2008-01-01

Full text: While high-dose of ionizing radiation is generally harmful and causes damage to living organisms some reports suggest low-dose of radiation may not be as damaging as previously thought. Despite increasing evidence regarding the protective effect of low-dose radiation, no studies have directly compared the exact dose-response pattern by high- and low-dose of radiation exposed at high-and low-dose rate. This study aims to explore the cellular and molecular changes in mice exposed to low- and high-dose of radiation exposed at low- and high-dose rate. When C57BL/6 mice (Female, 6 weeks) were exposed at high-dose rate, 0.8 Gy/min, no significant change on the level of WBC, RBC, or platelets was observed up to total dose of 0.5 Gy. However, 2 Gy of radiation caused dramatic reduction in the level of white blood cells (WBC) and platelets. This reduction was accompanied by increased DNA damage in hematopoietic environments. The reduction of WBC was mainly due to the reduction in the number of CD4+ T cells and CD19+ B cells. CD8+ T cells and NK cells appeared to be relatively resistant to high-dose of radiation. This change was also accompanied by the reduction of T- and B- progenitor cells in the bone marrow. In contrast, no significant changes of the number of CD4+ T, CD8+ T, NK, and B cells were observed in the spleen of mice exposed at low-dose-rate (0.7 m Gy/h or 3.95 mGy/h) for up to 2 Gy, suggesting that low-dose radiation does not alter cellular distribution in the spleen. Nevertheless, mice exposed to low-dose radiation exhibited elevation of VEGF, MCP-1, IL-4, Leptin, IL-3, and Tpo in the peripheral blood and slight increases in MIP-2, RANTES, and IL-2 in the spleen. This suggests that chronic γ-radiation can stimulate immune function without causing damage to the immune components of the body. Taken together, these data indicate hormesis of low-dose radiation, which could be attributed to the stimulation of immune function. Dose rate rather than total

LET effect on irradiation of hydroxyphthal imide in alcohol solutions

International Nuclear Information System (INIS)

Nakagawa, S.; Murakami, T.

2005-01-01

Hydroxyphthalimide(C 6 H 4 (CO) 2 -NOH) was irradiated with C ion (290MeV/u) in isopropyl alcohol, methanol, ethanol, and acetonitrile. LET was 13.2 and 26.5 keV/m. Dose was 5 and 10 kGy. A little amount of phthalimide was produced. The G value of the production of phthalimide by ion irradiation was less than that by -irradiation except for in methanol. In methanol solution, the production rate of phthalimide increased with increasing the value of LET. The amount of the substitution for C 6 H 4 (CO) 2 -NOD in methanol-d decreased by ion irradiation. These results suggest that the reaction mechanism in ion irradiation is different from -irradiation. (author)

Fast neutrons: Inexpensive and reliable tool to investigate high-LET particle radiobiology

International Nuclear Information System (INIS)

Gueulette, J.; Slabbert, J.P.; Bischoff, P.; Denis, J.M.; Wambersie, A.; Jones, D.

2010-01-01

Radiation therapy with carbon ions as well as missions into outer space have boosted the interest for high-LET particle radiobiology. Optimization of treatments in accordance with technical developments, as well as the radioprotection of cosmonauts during long missions require that research in these domains continue. Therefore suitable radiation fields are needed. Fast neutrons and carbon ions exhibit comparable LET values and similar radiobiological properties. Consequently, the findings obtained with each radiation quality could be shared to benefit knowledge in all concerned domains. The p(66+Be) neutron therapy facilities of iThemba LABS (South Africa) and the p(65)+Be neutron facility of Louvain-la-Neuve (Belgium) are in constant use to do radiobiological research for clinical applications with fast neutrons. These beams - which comply with all physical and technical requirements for clinical applications - are now fully reliable, easy to use and frequently accessible for radiobiological investigations. These facilities thus provide unique opportunities to undertake radiobiological experimentation, especially for investigations that require long irradiation times and/or fractionated treatments.

Relative biological effectiveness of high energy protons for a human melanoma

International Nuclear Information System (INIS)

Petrovic, I.; Ristic-Fira, A.; Todorovic, D.; Valastro, I.; Cirrone, P.; Cuttone, G.

2005-01-01

Relative biological effectiveness (RBE) for the survival of human melanoma cells induced by high linear energy transfer (LET) protons was investigated. Exponentially growing HTB140 cells were irradiated close to the Bragg peak maximum of the 62 MeV protons, as well as with 60 Co γ-rays, over single doses, ranging from 8-24 Gy. Clonogenic survival and cell viability were assessed up to 48 h post-irradiation, therefore considered as early inactivation effects. Dose dependent cell inactivation induced by high LET protons was observed. Surviving fractions have shown great overlapping with estimated cell viability, both with the increase of dose and with prolonged cell incubation. Evaluated RBEs were higher with the rise of dose, being in the range from 2 to 3. All analyzes performed have demonstrated a very radio-resistant nature of HTB140 melanoma cells. However, high LET protons are able to inactivate these cells in a larger extent compared to the effects of γ-rays. (author)

Total dose effects on the matching properties of deep submicron MOS transistors

International Nuclear Information System (INIS)

Wang Yuxin; Hu Rongbin; Li Ruzhang; Chen Guangbing; Fu Dongbing; Lu Wu

2014-01-01

Based on 0.18 μm MOS transistors, for the first time, the total dose effects on the matching properties of deep submicron MOS transistors are studied. The experimental results show that the total dose radiation magnifies the mismatch among identically designed MOS transistors. In our experiments, as the radiation total dose rises to 200 krad, the threshold voltage and drain current mismatch percentages of NMOS transistors increase from 0.55% and 1.4% before radiation to 17.4% and 13.5% after radiation, respectively. PMOS transistors seem to be resistant to radiation damage. For all the range of radiation total dose, the threshold voltage and drain current mismatch percentages of PMOS transistors keep under 0.5% and 2.72%, respectively. (semiconductor devices)

LET dependence of scintillation yields in liquid argon

Energy Technology Data Exchange (ETDEWEB)

Doke, Tadayoshi; Hitachi, Akira; Kikuchi, Jun; Crawford, H J; Lindstrom, P J; Masuda, Kimiaki; Shibamura, Eido; Takahashi, Tan

1988-06-01

Scintillation yields (scintillation intensity per unit absorbed energy) in liquid argon for ionizing particles are reviewed as a function of LET for the particles. The maximum scintillation yield, which is obtained for relativistic heavy ions from Ne to La, is about 1.2 times larger than that for gamma rays in NaI(Tl) crystal. In the low LET region, the scintillation yields for relativistic electrons, protons and He ions are 10-20% lower than the maximum yield. This tendency can be explained by taking into account the existence of the electrons which have escaped from their parent ions. In the high LET region, a quenching effect due to high ionization density is observed for alpha particles, fission fragments and relativistic Au ions.

Evaluation of accelerated test parameters for CMOS IC total dose hardness prediction

International Nuclear Information System (INIS)

Sogoyan, A.V.; Nikiforov, A.Y.; Chumakov, A.I.

1999-01-01

The approach to accelerated test parameters evaluation is presented in order to predict CMOS IC total dose behavior in variable dose-rate environment. The technique is based on the analytical model of MOSFET parameters total dose degradation. The simple way to estimate model parameter is proposed using IC's input-output MOSFET radiation test results. (authors)

The Lin28/let-7 axis regulates glucose metabolism

Science.gov (United States)

Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

2012-01-01

SUMMARY The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by blocking let-7 biogenesis. In studies of the Lin28/let-7 pathway, we discovered unexpected roles in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, whereas muscle-specific loss of Lin28a and overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance. These phenomena occurred in part through let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. The mTOR inhibitor rapamycin abrogated the enhanced glucose uptake and insulin-sensitivity conferred by Lin28a in vitro and in vivo. In addition, we found that let-7 targets were enriched for genes that contain SNPs associated with type 2 diabetes and fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. PMID:21962509

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-07-01

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

High-dose preoperative radiation for cancer of the rectum: Impact of radiation dose on patterns of failure and survival

International Nuclear Information System (INIS)

Ahmad, N.R.; Mohiuddin, M.; Marks, G.

1993-01-01

A variety of dose-time schedules are currently used for preoperative radiation therapy of rectal cancer. An analysis of patients treated with high-dose preoperative radiation therapy was undertaken to determine the influence of radiation dose on the patterns of failure, survival, and complications. Two hundred seventy-five patients with localized rectal cancer were treated with high-dose preoperative radiation therapy. One hundred fifty-six patients received 45 Gy (low-dose group). Since 1985, 119 patients with clinically unfavorable cancers were given a higher dose, 55 Gy using a shrinking field technique (high-dose group). All patients underwent curative resection. Median follow-up was 66 months in the low-dose group and 28 months in the high-dose group. Patterns of failure, survival, and complications were analyzed as a function of radiation dose. Fourteen percent of the total group developed a local recurrence; 20% in the low-dose group as compared with 6% in the high-dose group. The actuarial local recurrence rate at 5 years was 20% for the low-dose group and 8% for the high-dose group, and approached statistical significance with p = .057. For tethered/fixed tumors the actuarial local recurrence rates at 5 years were 28% and 9%, respectively, with p = .05. Similarly, for low-lying tumors (less than 6 cm from the anorectal junction) the rates were 24% and 9%, respectively, with p = .04. The actuarial rate of distant metastasis was 28% in the low-dose group and 20% in the high-dose group and was not significantly different. Overall actuarial 5-year survival for the total group of patients was 66%. No significant difference in survival was observed between the two groups, despite the higher proportion of unfavorable cancers in the high-dose group. The incidence of complications was 2%, equally distributed between the two groups. High-dose preoperative radiation therapy for rectal cancer results in excellent local control rates. 27 refs., 2 figs., 8 tabs

Efficiency of radical yield in alkylthymine and alkyluracil by high-LET irradiation

International Nuclear Information System (INIS)

Nakagawa, Seiko; Ohta, Nobuaki; Murakami, Takeshi

2010-01-01

Penthylthymines and hexyl-, nonyl-, and decyl- uracils were irradiated by C-ion (3.5 GeV) and γ-ray at 77 K. ESR spectra were measured to study radiation induced radicals in the temperature range from 108 to 273 K. A dihydro-5-yl (5-yl) radical formed by H addition to C6 carbon and a secondary alkyl radical by C-H bond fission at the second carbon from the end of the alkyl group were produced at 108 K. A dihydrouracil-6-yl (6-yl) radical formed by H addition to C5 carbon increased with increasing temperature for alkyluracils. The spectral feature obtained by C-ion irradiation was coincident with that by γ-irradiation. Total radical yields increased by alkylation and with increasing the length of alkyl chain. Yields of both 5-yl and secondary alkyl radicals irradiated by C-ion were less than those by γ-ray for penthylthymines and hexyluracil. On the contrary, radical yields were almost the same between ion and γ-ray irradiation for nonyl- and decyl-uracil. Mechanism of radical formation and effect of high-LET irradiation were discussed.

Dose equivalent distributions in the AAEC total body nitrogen facility

International Nuclear Information System (INIS)

Allen, B.J.; Bailey, G.M.; McGregor, B.J.

1985-01-01

The incident neutron dose equivalent in the AAEC total body nitrogen facility is measured by a calibrated remmeter. Dose equivalent rates and distributions are calculated by Monte Carlo techniques which take account of the secondary neutron flux from the collimator. Experiment and calculation are found to be in satisfactory agreement. The effective dose equivalent per exposure is determined by weighting organ doses, and the potential detriment per exposure is calculated from ICRP risk factors

Low-dose-rate total lymphoid irradiation: a new method of rapid immunosuppression

International Nuclear Information System (INIS)

Blum, J.E.; de Silva, S.M.; Rachman, D.B.; Order, S.E.

1988-01-01

Total Lymphoid Irradiation (TLI) has been successful in inducing immunosuppression in experimental and clinical applications. However, both the experimental and clinical utility of TLI are hampered by the prolonged treatment courses required (23 days in rats and 30-60 days in humans). Low-dose-rate TLI has the potential of reducing overall treatment time while achieving comparable immunosuppression. This study examines the immunosuppressive activity and treatment toxicity of conventional-dose-rate (23 days) vs low-dose-rate (2-7 days) TLI. Seven groups of Lewis rats were given TLI with 60Co. One group was treated at conventional-dose-rates (80-110 cGy/min) and received 3400 cGy in 17 fractions over 23 days. Six groups were treated at low-dose-rate (7 cGy/min) and received total doses of 800, 1200, 1800, 2400, 3000, and 3400 cGy over 2-7 days. Rats treated at conventional-dose-rates over 23 days and at low-dose-rate over 2-7 days tolerated radiation with minimal toxicity. The level of immunosuppression was tested using allogeneic (Brown-Norway) skin graft survival. Control animals retained allogeneic skin grafts for a mean of 14 days (range 8-21 days). Conventional-dose-rate treated animals (3400 cGy in 23 days) kept their grafts 60 days (range 50-66 days) (p less than .001). Low-dose-rate treated rats (800 to 3400 cGy total dose over 2-7 days) also had prolongation of allogeneic graft survival times following TLI with a dose-response curve established. The graft survival time for the 3400 cGy low-dose-rate group (66 days, range 52-78 days) was not significantly different from the 3400 cGy conventional-dose-rate group (p less than 0.10). When the total dose given was equivalent, low-dose-rate TLI demonstrated an advantage of reduced overall treatment time compared to conventional-dose-rate TLI (7 days vs. 23 days) with no increase in toxicity

New Insights into Fully-Depleted SOI Transistor Response During Total Dose Irradiation

International Nuclear Information System (INIS)

Burns, J.A.; Dodd, P.E.; Keast, C.L.; Schwank, J.R.; Shaneyfelt, M.R.; Wyatt, P.W.

1999-01-01

Worst-case bias configuration for total-dose testing fully-depleted SOI transistors was found to be process dependent. No evidence was found for total-dose induced snap back. These results have implications for hardness assurance testing

Biological dose estimation for charged-particle therapy using an improved PHITS code coupled with a microdosimetric kinetic model

International Nuclear Information System (INIS)

Sato, Tatsuhiko; Watanabe, Ritsuko; Kase, Yuki; Niita, Koji; Sihver, Lembit

2009-01-01

High-energy heavy ions (HZE particles) have become widely used for radiotherapy of tumors owing to their high biological effectiveness. In the treatment planning of such charged-particle therapy, it is necessary to estimate not only physical but also biological dose, which is the product of physical dose and relative biological effectiveness (RBE). In the Heavy-ion Medical Accelerator in Chiba (HIMAC), the biological dose is estimated by a method proposed by Kanai et al., which is based on the linear-quadratic (LQ) model with its parameters α and β determined by the dose distribution in terms of the unrestricted linear energy transfer (LET). Thus, RBE is simply expressed as a function of LET in their model. However, RBE of HZE particles cannot be uniquely determined from their LET because of their large cross sections for high-energy δ-ray production. Hence, development of a biological dose estimation model that can explicitly consider the track structure of δ-rays around the trajectory of HZE particles is urgently needed. Microdosimetric quantities such as lineal energy y are better indexes for representing RBE of HZE particles in comparison to LET, since they can express the decrease of ionization densities around their trajectories due to the production of δ-rays. The difference of the concept between LET and y is illustrated in Figure 1. However, the use of microdosimetric quantities in computational dosimetry was severely limited because of the difficulty in calculating their probability densities (PDs) in macroscopic matter. We therefore improved the 3-dimensional particle transport simulation code PHITS, providing it with the capability of estimating the microdosimetric PDs in a macroscopic framework by incorporating a mathematical function that can instantaneously calculate the PDs around the trajectory of HZE particles with precision equivalent to a microscopic track-structure simulation. A new method for estimating biological dose from charged

Real-time Molecular Study of Bystander Effects of Low dose Low LET radiation Using Living Cell Imaging and Nanoparticale Optics

Energy Technology Data Exchange (ETDEWEB)

Natarajan, Mohan [UT Health Science Center at San Antonio; Xu, Nancy R [Old Dominion University; Mohan, Sumathy [UT Health Science Center at San Antonio

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

The Role of Electron Transport and Trapping in MOS Total-Dose Modeling

International Nuclear Information System (INIS)

Fleetwood, D.M.; Winokur, P.S.; Riewe, L.C.; Flament, O.; Paillet, P.; Leray, J.L.

1999-01-01

Radiation-induced hole and electron transport and trapping are fundamental to MOS total-dose models. Here we separate the effects of electron-hole annihilation and electron trapping on the neutralization of radiation-induced charge during switched-bias irradiation for hard and soft oxides, via combined thermally stimulated current (TSC) and capacitance-voltage measurements. We also show that present total-dose models cannot account for the thermal stability of deeply trapped electrons near the Si/SiO 2 interface, or the inability of electrons in deep or shallow traps to contribute to TSC at positive bias following (1) room-temperature, (2) high-temperature, or (3) switched-bias irradiation. These results require revisions of modeling parameters and boundary conditions for hole and electron transport in SiO 2 . The nature of deep and shallow electron traps in the near-interfacial SiO 2 is discussed

Simulation experiment on total ionization dose effects of linear CCD

International Nuclear Information System (INIS)

Tang Benqi; Zhang Yong; Xiao Zhigang; Wang Zujun; Huang Shaoyan

2004-01-01

We carry out the ionization radiation experiment of linear CCDs operated in unbiased, biased, biased and driven mode respectively by Co-60 γ source with our self-designed test system, and offline test the Dark signal and Saturation voltage and SNR varied with total dose for TCD132D, and get some valuable results. On the basis of above work, we set forth a primary experiment approaches to simulate the total dose radiation effects of charge coupled devices. (authors)

The radiobiology of boron neutron capture therapy: Are ''photon-equivalent'' doses really photon-equivalent?

International Nuclear Information System (INIS)

Coderre, J.A.; Diaz, A.Z.; Ma, R.

2001-01-01

Boron neutron capture therapy (BNCT) produces a mixture of radiation dose components. The high-linear energy transfer (LET) particles are more damaging in tissue than equal doses of low-LET radiation. Each of the high-LET components can multiplied by an experimentally determined factor to adjust for the increased biological effectiveness and the resulting sum expressed in photon-equivalent units (Gy-Eq). BNCT doses in photon-equivalent units are based on a number of assumptions. It may be possible to test the validity of these assumptions and the accuracy of the calculated BNCT doses by 1) comparing the effects of BNCT in other animal or biological models where the effects of photon radiation are known, or 2) if there are endpoints reached in the BNCT dose escalation clinical trials that can be related to the known response to photons of the tissue in question. The calculated Gy-Eq BNCT doses delivered to dogs and to humans with BPA and the epithermal neutron beam of the Brookhaven Medical Research Reactor were compared to expected responses to photon irradiation. The data indicate that Gy-Eq doses in brain may be underestimated. Doses to skin are consistent with the expected response to photons. Gy-Eq doses to tumor are significantly overestimated. A model system of cells in culture irradiated at various depths in a lucite phantom using the epithermal beam is under development. Preliminary data indicate that this approach can be used to detect differences in the relative biological effectiveness of the beam. The rat 9L gliosarcoma cell survival data was converted to photon-equivalent doses using the same factors assumed in the clinical studies. The results superimposed on the survival curve derived from irradiation with Cs-137 photons indicating the potential utility of this model system. (author)

Oxygen as a product of water radiolysis in high-LET tracks. II. Radiobiological implications

International Nuclear Information System (INIS)

Baverstock, K.F.; Burns, W.G.

1981-01-01

Consideration is given to the possibility that molecular oxygen generated in the tracks of energetic heavy ions is responsible for the reduction in oxygen enhancement ratio (OER) with increasing linear energy transfer (LET) observed for the loss of reproductive capacity caused by radiation in many cellular organisms. Yields of oxygen relationship of OER to LET for two organisms, Chlamydomonas reinhardii and Shigella flexneri, using a simple diffusion kinetic model for radiobiological action which takes account of the diffusion of oxygen after its formation. The results of these calculations show that the model accounts well for the shape of the OER vs. LET relationship

Hyperfractionated high-dose total body irradiation in bone marrow transplantation for Ph{sup 1}-positive acute lymphoblastic leukemia

Energy Technology Data Exchange (ETDEWEB)

Kikuchi, Akira; Ebihara, Yasuhiro; Mitsui, Tetsuo [Tokyo Univ. (Japan). Hospital of the Institute of Medical Science] [and others

1998-12-01

In two cases of Philadelphia-positive childhood acute lymphoblastic leukemia (Ph{sup 1} ALL), we performed allogeneic bone marrow transplantation (AlloBMT) with preconditioning regimen, including hyperfractionated high-dose total body irradiation (TBI) (13.5 Gy, in 9 fractions). Their disease statuses at BMT were hematological relapse in case 1 and molecular relapse in case 2. Bone marrow donors were unrelated in case 1, and HLA was a partially mismatched mother in case 2. Regimen-related toxicity was tolerable in both cases. Hematological recovery was rapid, and engraftment was obtained on day 14 in case 1 and on day 12 in case 2. BCR/ABL message in bone marrow disappeared on day 89 in case 1 and on day 19 in case 2 and throughout their subsequent clinical courses. Although short-term MTX and Cy-A continuous infusion were used for GVHD prophylaxis, grade IV GVHD was observed in case 1 and grade III in case 2. Both cases experienced hemorrhagic cystitis because of adenovirus type 11 infection. Although case 1 died of interstitial pneumonitis on day 442, case 2 has been free of disease through day 231. AlloBMT for Ph{sup 1} ALL with preconditioning regimen including hyperfractionated high-dose TBI is considered to be worth further investigation. (author)

Early and long-term effects of low- and high-LET radiation on rat behavior and monoamine metabolism in different brain regions

Science.gov (United States)

Belov, Oleg

Space radiation is one of the factors representing a significant health risk to the astronauts during deep-space missions. A most harmful component of space radiation beyond the Earth's magnetosphere is the galactic cosmic rays which are composed of high-energy protons, α particles, and high charge and energy (HZE) nuclei. Recent studies performed at particle accelerators have revealed a significant impact of HZE nuclei on the central nervous system and, in particular, on the cognitive functions. However the exact molecular mechanisms behind the observed impairments remain mostly unclear. This research is focused on study of early and long-term effects of low- and high-linear-energy-transfer (LET) radiation on the rat behavior and monoamine metabolism in the brain regions involved in behavior and motor control and form emotional and motivational states. Different groups of rats were whole-body exposed to 500 MeV/u (12) C particles (LET 10.6 keV/µm) available at the Nuclotron accelerator of the Joint Institute for Nuclear Research (Dubna, Russia) and to gamma rays at the equivalent dose of 1 Gy. An additional group of animals was sham-irradiated and considered as a control. The isolated brain regions have included the prefrontal cortex, nucleus accumbens, hypothalamus, hippocampus, and striatum where we determined the concentrations of noradrenalin, dopamine and its metabolites 3,4-doxyphenylacetic acid, homovanillic acid, and 3-methoxytyramine and serotonin and its metabolite 5-hydroxyindoleacetic acid. The following effects were observed in the different periods after irradiation. 1 day after exposure to (12) C particles strong changes in the concentration of monoamines and their metabolites were observed in three structures, namely, the prefrontal cortex, nucleus accumbens, and hippocampus. However, significant changes were found in the prefrontal cortex and weaker changes were seen in the nucleus accumbens, whereas changes were insignificant in the hippocampus

TH-CD-201-03: A Real-Time Method to Simultaneously Measure Linear Energy Transfer and Dose for Proton Therapy Using Organic Scintillators

Energy Technology Data Exchange (ETDEWEB)

Alsanea, F; Therriault-Proulx, F; Sawakuchi, G; Beddar, S [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: The light generated in organic scintillators depends on both the radiation dose and the linear energy transfer (LET). The LET dependence leads to an under-response of the detector in the Bragg peak of proton beams. This phenomenon, called ionization quenching, must be corrected to obtain accurate dose measurements of proton beams. This work exploits the ionization quenching phenomenon to provide a method of measuring LET and auto correcting quenching. Methods: We exposed simultaneously four different organic scintillators (BCF-12, PMMA, PVT, and LSD; 1mm in diameter) and a plane parallel ionization chamber in passively scattered proton beams to doses between 32 and 43 cGy and fluence averaged LET values from 0.47 to 1.26 keV/µm. The LET values for each irradiation condition were determined using a validated Monte Carlo model of the beam line. We determined the quenching parameter in the Birk’s equation for scintillation in BCF-12 for dose measurements. One set of irradiation conditions was used to correlate the scintillation response ratio to the LET values and plot a scintillation response ratio versus LET calibration curve. Irradiation conditions independent from the calibration ones were used to validate this method. Comparisons to the expected values were made on both the basis of dose and LET. Results: Among all the scintillators investigated, the ratio of PMMA to BCF-12 provided the best correlation to LET values and was used as the LET calibration curve. The expected LET values in the validation set were within 2%±6%, which resulted in dose accuracy of 1.5%±5.8% for the range of LET values investigated in this work. Conclusion: We have demonstrated the feasibility of using the ratio between the light output of two organic scintillators to simultaneously measure LET and dose of therapeutic proton beams. Further studies are needed to verify the response in higher LET values.

The antiproton depth–dose curve in water

CERN Document Server

Bassler, N; Jäkel, O; Knudsen, H V; Kovacevic, S

2008-01-01

We have measured the depth–dose curve of 126 MeV antiprotons in a water phantom using ionization chambers. Since the antiproton beam provided by CERN has a pulsed structure and possibly carries a high-LET component from the antiproton annihilation, it is necessary to correct the acquired charge for ion recombination effects. The results are compared with Monte Carlo calculations and were found to be in good agreement. Based on this agreement we calculate the antiproton depth–dose curve for antiprotons and compare it with that for protons and find a doubling of the physical dose in the peak region for antiprotons.

Total dose meter development

International Nuclear Information System (INIS)

Brackenbush, L.W.

1986-09-01

This report describes an alarming ''pocket'' monitor/dosimeter, based on a tissue-equivalent proportional counter, that measure both neutron and gamma dose and determines dose equivalent for the mixed radiation field. This report details the operation of the device and provides information on: the necessity for a device to measure dose equivalent in mixed radiation fields; the mathematical theory required to determine dose equivalent from tissue equivalent proportional; the detailed electronic circuits required; the algorithms required in the microprocessor used to calculate dose equivalent; the features of the instrument; program accomplishments and future plans

Single event effects and total ionizing dose effects of typical VDMOSFET devices

International Nuclear Information System (INIS)

Lou Jianshe; Cai Nan; Liu Jiaxin; Wu Qinzhi; Wang Jia

2012-01-01

In this work, single event effects and total ionizing dose effects of typical VDMOSFET irradiated by 60 Co γ-rays and 252 Cf source were studied. The single event burnout and single event gate rupture (SEB/SEGR) effects were investigated, and the relationship between drain-source breakdown voltage and ionizing dose was obtained. The results showed that the VDMOSFET devices were sensitive to SEB and SEGR, and measures to improve their resistance to SEB and SEGR should be considered seriously for their space applications. The drain-source breakdown voltage was sensitive to total ionizing dose effects as the threshold voltage. In assessing the devices' resistance to the total ionizing dose effects, both the threshold voltage and the drain-source breakdown voltage should be taken into account. (authors)

Pocket total dose meter

International Nuclear Information System (INIS)

Brackenbush, L.W.; Endres, G.W.R.

1984-10-01

Laboratory measurements have demonstrated that it is possible to simultaneously measure absorbed dose and dose equivalent using a single tissue equivalent proportional counter. Small, pocket sized instruments are being developed to determine dose equivalent as the worker is exposed to mixed field radiation. This paper describes the electronic circuitry and computer algorithms used to determine dose equivalent in these devices

Enchanced total dose damage in junction field effect transistors and related linear integrated circuits

International Nuclear Information System (INIS)

Flament, O.; Autran, J.L.; Roche, P.; Leray, J.L.; Musseau, O.

1996-01-01

Enhanced total dose damage of Junction Field-effect Transistors (JFETs) due to low dose rate and/or elevated temperature has been investigated for elementary p-channel structures fabricated on bulk and SOI substrates as well as for related linear integrated circuits. All these devices were fabricated with conventional junction isolation (field oxide). Large increases in damage have been revealed by performing high temperature and/or low dose rate irradiations. These results are consistent with previous studies concerning bipolar field oxides under low-field conditions. They suggest that the transport of radiation-induced holes through the oxide is the underlying mechanism. Such an enhanced degradation must be taken into account for low dose rate effects on linear integrated circuits

Doses and fractionation schemes to be employed in clinical trials of high-LET radiations

International Nuclear Information System (INIS)

Fowler, J.F.

1979-01-01

An improvement in local tumour control of 20% would require 2 x 130 cases in order that nine trials out of ten should show the difference at a significant level. If the improvement is 30% only 2 x 55 patients are required. However, the detection of increased normal tissue complications requires larger number of patients than this, e.g. 2 x 150 if the increase is from 5% to 15%. The use of two dose levels on the neutron side in a clinical trial would enable definitive data to be obtained in, say, 6 years with 300 patients, instead of 10 years with 400 patients if only one dose level were used. (author)

Spectra of the linear energy transfer measured with a track etch spectrometer in the beam of 1 GeV protons and the contribution of secondary charged particles to the dose

International Nuclear Information System (INIS)

Spurny, F.; Vlcek, B.; Bamblevskij, V.P.; Timoshenko, G.N.

1999-01-01

A spectrometer of the linear energy transfer (LET) on the base of CR-39 detector was used to establish the spectra of LET in the beam of protons with the primary energy of 1 GeV. It was found out that the LET spectra of secondary charged particles between 100 and 7000 MeV cm 2 g -1 do not depend on the radiator. The average quality factors for the LET region mentioned were obtained about 11.6 with ICRP 26 quality factors and about 14.0 with ICRP 60 quality factors. The spectra obtained permitted to calculate the contributions of these secondary charged particles to the dosimetric quantities. It was observed that these contributions were about 7.0% for the total absorbed dose of protons and close 90% in the case of the equivalent doses. It is more than it was found out for few hundred MeV protons

Let's Poem: The Essential Guide to Teaching Poetry in a High-Stakes, Multimodal World (Middle through High School). Language & Literacy Practitioners Bookshelf

Science.gov (United States)

Dressman, Mark

2010-01-01

This cutting-edge guide presents multiple approaches to teaching poetry at the middle and high school levels. The author provides field-tested activities with detailed how-to instructions, as well as advice for how educators can "justify" their teaching within a high-stakes curriculum environment. "Let's Poem" will show pre- and inservice teachers…

A combination of high dose rate (10X FFF/2400 MU/min/10 MV X-rays) and total low dose (0.5 Gy) induces a higher rate of apoptosis in melanoma cells in vitro and superior preservation of normal melanocytes.

Science.gov (United States)

Sarojini, Sreeja; Pecora, Andrew; Milinovikj, Natasha; Barbiere, Joseph; Gupta, Saakshi; Hussain, Zeenathual M; Tuna, Mehmet; Jiang, Jennifer; Adrianzen, Laura; Jun, Jaewook; Catello, Laurice; Sanchez, Diana; Agarwal, Neha; Jeong, Stephanie; Jin, Youngjin; Remache, Yvonne; Goy, Andre; Ndlovu, Alois; Ingenito, Anthony; Suh, K Stephen

2015-10-01

The aim of this study was to determine the apoptotic effects, toxicity, and radiosensitization of total low dose irradiation delivered at a high dose rate in vitro to melanoma cells, normal human epidermal melanocytes (HEM), or normal human dermal fibroblasts (HDF) and to study the effect of mitochondrial inhibition in combination with radiation to enhance apoptosis in melanoma cells. Cells irradiated using 10X flattening filter-free (FFF) 10 MV X-rays at a dose rate of 400 or 2400 MU/min and a total dose of 0.25-8 Gy were analyzed by cell/colony counting, MitoTracker, MTT, and DNA-damage assays, as well as by quantitative real-time reverse transcriptase PCR in the presence or absence of mitochondrial respiration inhibitors. A dose rate of 2400 MU/min killed on average five-fold more melanoma cells than a dose rate 400 MU/min at a total dose of 0.5 Gy and preserved 80% survival of HEM and 90% survival of HDF. Increased apoptosis at the 2400 MU/min dose rate is mediated by greater DNA damage, reduced cell proliferation, upregulation of apoptotic genes, and downregulation of cell cycle genes. HEM and HDF were relatively unharmed at 2400 MU/min. Radiation induced upregulation of mitochondrial respiration in both normal and cancer cells, and blocking the respiration with inhibitors enhanced apoptosis only in melanoma cells. A high dose rate with a low total dose (2400 MU/min, 0.5 Gy/10X FFF 10 MV X-rays) enhances radiosensitivity of melanoma cells while reducing radiotoxicity toward HEM and HDF. Selective cytotoxicity of melanoma cells is increased by blocking mitochondrial respiration.

Use of normalized total dose to represent the biological effect of fractionated radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Flickinger, J C; Kalend, A [Pittsburgh University School of Medicine (USA). Department of Radiation Oncology Pittsburg Cancer Institute (USA)

1990-03-01

There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented. (author). 51 refs.; 1 fig.; 1 tab.

Use of normalized total dose to represent the biological effect of fractionated radiotherapy

International Nuclear Information System (INIS)

Flickinger, J.C.; Kalend, A.

1990-01-01

There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented. (author). 51 refs.; 1 fig.; 1 tab

Influence of LET on repair of DNA damages in Deinococcus radiodurans

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Y; Tanaka, A; Kikuchi, M; Shimizu, T; Watanabe, H [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment; Cao, J P; Taucher-Scholz, G

1997-03-01

Inactivation caused by heavy ions was studied in dry cells of radioresistant bacterium Deinococcus radiodurans. All survival curves were characterized by a large shoulder of the curves. No final slopes of the exponential part of survival curves for heavy ion irradiation were steeper than that for 2.0 MeV electron irradiation. The plots of RBE versus LET showed no obvious peaks, suggesting that this bacterium can repair not only DNA double strand breaks (DSBs) but also clustered damage in DNA which may be induced by heavy ions. The genomic DNA of D. radiodurans was cleaved into large fragments with restriction enzyme Not I after post-irradiation incubation and the fragments were separated using pulsed-field gel electrophoresis (PFGE). DSBs induction and rejoining process were analyzed by detection of the reappearance of ladder pattern of DNA fragments. The required repair time after heavy ions irradiation was longer than the repair time for electrons at the same dose of irradiation, however, the rate of repair enzyme induction was almost similar to each other between electrons and heavy ions, suggesting that the same repair system is likely to be used after both low and high LET irradiations. (author)

A dose-response curve for biodosimetry from a 6 MV electron linear accelerator

Energy Technology Data Exchange (ETDEWEB)

Lemos-Pinto, M.M.P.; Cadena, M.; Santos, N.; Fernandes, T.S.; Borges, E.; Amaral, A., E-mail: marcelazoo@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departamento de Energia Nuclear

2015-10-15

Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates. (author)

A dose-response curve for biodosimetry from a 6 MV electron linear accelerator.

Science.gov (United States)

Lemos-Pinto, M M P; Cadena, M; Santos, N; Fernandes, T S; Borges, E; Amaral, A

2015-10-01

Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates.

Induction of λ prophage in lysogenic E.Coli exposed to ionizing radiation of different let

International Nuclear Information System (INIS)

Bonev, M.; Kozubek, S.; Krasavin, E.A.; Cherevatenko, A.P.

1988-01-01

Induction of λ prophage in lysogenic E. coli cells exposed to ionizing radiation of different LET was studied as a function of dose I(D). Activities of pleiotropic RecA protein were shown to contribute to the shape of the I(D) curve. The experimental data were fitted by the function I(D)=αD(1-exp(-D 0 -1 xD))exp(-βD). Inducibility α increased with increasing LET which was related to the increased incidence of DNA lesions being a SOS - system call

Long-term brain structural magnetic resonance imaging and cognitive functioning in children treated for acute lymphoblastic leukemia with high-dose methotrexate chemotherapy alone or combined with CNS radiotherapy at reduced total dose to 12 Gy

Energy Technology Data Exchange (ETDEWEB)

Zajac-Spychala, Olga; Pilarczyk, Jakub; Derwich, Katarzyna; Wachowiak, Jacek [Poznan University of Medical Sciences, Department of Pediatric Oncology, Hematology and Transplantology, Poznan (Poland); Pawlak, Mikolaj A. [Poznan University of Medical Sciences, Department of Neurology and Cerebrovascular Disorders, Poznan (Poland); Karmelita-Katulska, Katarzyna [Poznan University of Medical Sciences, Department of Neuroradiology, Poznan (Poland)

2017-02-15

The aim of this study was to assess the long-term side effects of central nervous system prophylaxis (high-dose chemotherapy alone vs chemotherapy and CNS radiotherapy) according to the ALL IC-BFM 2002. Thirty-tree children aged 6.7-19.9 years have been studied. The control group consisted of 12 children newly diagnosed with acute lymphoblastic leukemia. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between two therapeutic schemes and patients prior to treatment. Patients treated with chemotherapy and CNS radiotherapy had smaller hippocampi than two other subgroups and lower IQ score than patients treated with chemotherapy alone. Both treated groups, whether with chemotherapy only or in combination with CNS radiotherapy, had significantly lower volumes of caudate nucleus and performed significantly worse on measures of verbal fluency in comparison with patients prior to treatment. There were no differences in the mean volumes of total white matter, total gray matter, thalamus, putamen, and amygdala between the studied groups. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment was observed, especially in children who received chemotherapy in combination with reduced dose CNS radiotherapy. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment were observed, especially in children who received chemotherapy in combination with CNS radiotherapy. (orig.)

Long-term brain structural magnetic resonance imaging and cognitive functioning in children treated for acute lymphoblastic leukemia with high-dose methotrexate chemotherapy alone or combined with CNS radiotherapy at reduced total dose to 12 Gy

International Nuclear Information System (INIS)

Zajac-Spychala, Olga; Pilarczyk, Jakub; Derwich, Katarzyna; Wachowiak, Jacek; Pawlak, Mikolaj A.; Karmelita-Katulska, Katarzyna

2017-01-01

The aim of this study was to assess the long-term side effects of central nervous system prophylaxis (high-dose chemotherapy alone vs chemotherapy and CNS radiotherapy) according to the ALL IC-BFM 2002. Thirty-tree children aged 6.7-19.9 years have been studied. The control group consisted of 12 children newly diagnosed with acute lymphoblastic leukemia. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between two therapeutic schemes and patients prior to treatment. Patients treated with chemotherapy and CNS radiotherapy had smaller hippocampi than two other subgroups and lower IQ score than patients treated with chemotherapy alone. Both treated groups, whether with chemotherapy only or in combination with CNS radiotherapy, had significantly lower volumes of caudate nucleus and performed significantly worse on measures of verbal fluency in comparison with patients prior to treatment. There were no differences in the mean volumes of total white matter, total gray matter, thalamus, putamen, and amygdala between the studied groups. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment was observed, especially in children who received chemotherapy in combination with reduced dose CNS radiotherapy. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment were observed, especially in children who received chemotherapy in combination with CNS radiotherapy. (orig.)

A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.

Science.gov (United States)

Rørvik, Eivind; Thörnqvist, Sara; Stokkevåg, Camilla H; Dahle, Tordis J; Fjaera, Lars Fredrik; Ytre-Hauge, Kristian S

2017-06-01

The relative biological effectiveness (RBE) of protons varies with the radiation quality, quantified by the linear energy transfer (LET). Most phenomenological models employ a linear dependency of the dose-averaged LET (LET d ) to calculate the biological dose. However, several experiments have indicated a possible non-linear trend. Our aim was to investigate if biological dose models including non-linear LET dependencies should be considered, by introducing a LET spectrum based dose model. The RBE-LET relationship was investigated by fitting of polynomials from 1st to 5th degree to a database of 85 data points from aerobic in vitro experiments. We included both unweighted and weighted regression, the latter taking into account experimental uncertainties. Statistical testing was performed to decide whether higher degree polynomials provided better fits to the data as compared to lower degrees. The newly developed models were compared to three published LET d based models for a simulated spread out Bragg peak (SOBP) scenario. The statistical analysis of the weighted regression analysis favored a non-linear RBE-LET relationship, with the quartic polynomial found to best represent the experimental data (P = 0.010). The results of the unweighted regression analysis were on the borderline of statistical significance for non-linear functions (P = 0.053), and with the current database a linear dependency could not be rejected. For the SOBP scenario, the weighted non-linear model estimated a similar mean RBE value (1.14) compared to the three established models (1.13-1.17). The unweighted model calculated a considerably higher RBE value (1.22). The analysis indicated that non-linear models could give a better representation of the RBE-LET relationship. However, this is not decisive, as inclusion of the experimental uncertainties in the regression analysis had a significant impact on the determination and ranking of the models. As differences between the models were

Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation

International Nuclear Information System (INIS)

Turesson, I.

1990-01-01

The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose-rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell-cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterized by α/β values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore

Dose calculation method with 60-cobalt gamma rays in total body irradiation

International Nuclear Information System (INIS)

Scaff, Luiz Alberto Malaguti

2001-01-01

Physical factors associated to total body irradiation using 60 Co gamma rays beams, were studied in order to develop a calculation method of the dose distribution that could be reproduced in any radiotherapy center with good precision. The method is based on considering total body irradiation as a large and irregular field with heterogeneities. To calculate doses, or doses rates, of each area of interest (head, thorax, thigh, etc.), scattered radiation is determined. It was observed that if dismagnified fields were considered to calculate the scattered radiation, the resulting values could be applied on a projection to the real size to obtain the values for dose rate calculations. In a parallel work it was determined the variation of the dose rate in the air, for the distance of treatment, and for points out of the central axis. This confirm that the use of the inverse square law is not valid. An attenuation curve for a broad beam was also determined in order to allow the use of absorbers. In this work all the adapted formulas for dose rate calculations in several areas of the body are described, as well time/dose templates sheets for total body irradiation. The in vivo dosimetry, proved that either experimental or calculated dose rate values (achieved by the proposed method), did not have significant discrepancies. (author)

Total-dose hardness assurance for low earth orbit

International Nuclear Information System (INIS)

Maurer, R.H.; Suter, J.J.

1987-01-01

The Low Earth Orbit radiation environment has two significant characteristics that make laboratory simulation exposures difficult: (1) a low dose rate and (2) many cycles of low dose accumulation followed by dose-free annealing. Hardness assurance considerations for this environment are discussed and related to data from the testing of Advanced Low Power Schottky and High-speed CMOS devices

HAMLET -Matroshka IIA and IIB experiments aboard the ISS: comparison of organ doses

Science.gov (United States)

Kato, Zoltan; Reitz, Guenther; Berger, Thomas; Bilski, Pawel; Hajek, Michael; Sihver, Lembit; Palfalvi, Jozsef K.; Hager, Luke; Burmeister, Soenke

The Matroshka experiments and the related FP7 HAMLET project aimed to study the dose burden of the cosmic rays in the organs of the crew working inside and outside the ISS. Two of the experiments will be discussed. They were performed in two different locations inside the ISS: during the Matroshka 2A (in 2006) the phantom was stored in the Russian Docking Module (Pirs), while during the Matroshka 2B (in 2007-08) it was inside the Russian Service Module (Zvezda). Both experiments were performed in the decreasing phase of the solar cycle. Solid state nuclear track detectors (SSNTD) were applied to investigate the dose contribution of the high LET radiation above ˜10 keV/µm. Two configurations of SSNTDs stacks were constructed: one for the exposure in the so called organ dose boxes (in the lung and kidney), another one for the skin dose measurements, embedded in the nomex poncho of the Phantom. In addition a reference package was placed outside the phantom. After exposure the detectors were transferred to the Earth for data evaluation. Short and long etching procedures were applied to distinguish the high and low LET particles, respectively. The particle tracks were evaluated by a semi automated image analyzer. Addi-tionally manual track parameter measurements were performed on very long tracks. As the result of measurements the LET spectra were deduced. Based on these spectra, the absorbed dose, the dose equivalent and the mean quality factor were calculated. The configuration of the stacks, the methods of the calibration and evaluation and finally the results will be presented and compared. The multiple etching and the combined evaluation method allowed to determine the fraction of the dose originated from HZE particles (Z>2 and range > major axis). Further on, data eval-uation was performed to separate the secondary particles (target fragments) from the primary particles. Although the number of high LET particles above a ˜80 keV/µm was found to be higher during

Calculation of complication probability of pion treatment at PSI using dose-volume histograms

International Nuclear Information System (INIS)

Nakagawa, Keiichi; Akanuma, Atsuo; Aoki, Yukimasa

1991-01-01

In the conformation technique a target volume is irradiated uniformly as in conventional radiations, whereas surrounding tissue and organs are nonuniformly irradiated. Clinical data on radiation injuries that accumulate with conventional radiation are not applicable without appropriate compensation. Recently a putative solution of this problem was proposed by Lyman using dose-volume histograms. This histogram reduction method reduces a given dose-volume histogram of an organ to a single step which corresponds to the equivalent complication probability by interpolation. As a result it converts nonuniform radiation into a unique dose to the whole organ which has the equivalent likelihood of radiation injury. This method is based on low LET radiation with conventional fractionation schedules. When it is applied to high LET radiation such as negative pion treatment, a high LET dose should be converted to an equivalent photon dose using an appropriate value of RBE. In the present study the histogram reduction method was applied to actual patients treated by the negative pion conformation technique at the Paul Scherrer Institute. Out of evaluable 90 cases of pelvic tumors, 16 developed grade III-IV bladder injury, and 7 developed grade III-IV rectal injury. The 90 cases were divided into roughly equal groups according to the equivalent doses to the entire bladder and rectum. Complication rates and equivalent doses to the full organs in these groups could be represented by a sigmoid dose-effect relation. When RBE from a pion dose to a photon dose is assumed to be 2.1 for bladder injury, the rates of bladder complications fit best to the theoretical complication curve. When the RBE value was 2.3, the rates of rectal injury fit the theoretical curve best. These values are close to the conversion factor of 2.0 that is used in clinical practice at PSI. This agreement suggests the clinical feasibility of the histogram reduction method in conformation radiotherapy. (author)

Diffusion-kinetic theories for LET effects on the radiolysis of water

International Nuclear Information System (INIS)

Pimblott, S.M.; LaVerne, J.A.

1994-01-01

Diffusion-kinetic methods are used to investigate the effects of incident particle linear energy transfer (LET) on the radiolysis of water and aqueous solutions. Chemically realistic deterministic diffusion-kinetic calculations examining the scavenging capacity dependences of the scavenged yield of e aq - and of OH demonstrate that the scavenged yields are related to the underlying time-dependent kinetics in the absence of the scavenger by a simple Laplace transform relationship. This relationship is also shown to link the effect of an e eq - scavenger on the formation of H 2 with the time dependence of H 2 production in the absence of the scavenger. The simple Laplace relationship does not work well when applied to H 2 O 2 formation in high-LET particle tracks even though such a relationship is valid with low-LET particles. It is found that while the secondary reaction of H 2 O 2 with e aq - can be neglected in low-LET particle radiolysis, it is of considerable significance in the tracks produced by high-LET particles. The increased importance of this reaction with increasing LET is the major reason for the failure of the Laplace relationship for H 2 O 2 . 55 refs., 9 figs., 2 tabs

A radiobiological approach to cancer treatment. Possible chemical and physical agents modifying radiosensitivity in comparison with high LET radiations

International Nuclear Information System (INIS)

Sugahara, T.

1982-01-01

Biological characteristics of high LET radiations are summarized to be low oxygen enhancement ratio, high RBE, low repair and low cell cycle dependency of radiosensitivity. Various chemical modifiers of radiosensitivity and radiological effect of hyperthermia are classified into these four properties. It is evident that we have now various means to mimic high LET radiations as far as biological response is concerned though some of them are still in experimental stage. Among them, the means to cope with hypoxia and repair which are assumed to be the most important causes of radioresistance of human tumors are discussed in some detail. It is expected that through the present seminar we would have consensus to concentrate our effort of development for new modifying means available and useful in developing countries. (author)

Calculation of midplane dose for total body irradiation from entrance and exit dose MOSFET measurements.

Science.gov (United States)

Satory, P R

2012-03-01

This work is the development of a MOSFET based surface in vivo dosimetry system for total body irradiation patients treated with bilateral extended SSD beams using PMMA missing tissue compensators adjacent to the patient. An empirical formula to calculate midplane dose from MOSFET measured entrance and exit doses has been derived. The dependency of surface dose on the air-gap between the spoiler and the surface was investigated by suspending a spoiler above a water phantom, and taking percentage depth dose measurements (PDD). Exit and entrances doses were measured with MOSFETs in conjunction with midplane doses measured with an ion chamber. The entrance and exit doses were combined using an exponential attenuation formula to give an estimate of midplane dose and were compared to the midplane ion chamber measurement for a range of phantom thicknesses. Having a maximum PDD at the surface simplifies the prediction of midplane dose, which is achieved by ensuring that the air gap between the compensator and the surface is less than 10 cm. The comparison of estimated midplane dose and measured midplane dose showed no dependence on phantom thickness and an average correction factor of 0.88 was found. If the missing tissue compensators are kept within 10 cm of the patient then MOSFET measurements of entrance and exit dose can predict the midplane dose for the patient.

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

Science.gov (United States)

Powers, John T; Tsanov, Kaloyan M; Pearson, Daniel S; Roels, Frederik; Spina, Catherine S; Ebright, Richard; Seligson, Marc; de Soysa, Yvanka; Cahan, Patrick; Theiβen, Jessica; Tu, Ho-Chou; Han, Areum; Kurek, Kyle C; LaPier, Grace S; Osborne, Jihan K; Ross, Samantha J; Cesana, Marcella; Collins, James J; Berthold, Frank; Daley, George Q

2016-01-01

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumor suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. However, here we show that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN mRNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN-amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma pathogenesis with broad implications for cancer pathogenesis. PMID:27383785

Dose-rate effects on the bulk etch-rate of CR-39 track detector exposed to low-LET radiations

CERN Document Server

Yamauchi, T; Oda, K; Ikeda, T; Honda, Y; Tagawa, S

1999-01-01

The effect of gamma-rays and pulsed electrons has been investigated on the bulk etch rate of CR-39 detector at doses up to 100 kGy under various dose-rate between 0.0044 and 35.0 Gy/s. The bulk etch rate increased exponentially with the dose at every examined dose-rates. It was reveled to be strongly depend on the dose-rate: the bulk etch rate was decreased with increasing dose-rate at the same total dose. A primitive model was proposed to explain the dose-rate effect in which oxygen dissolved was assumed to dominate the damage formation process.

An experimental study on total dose effects in SRAM-based FPGAs

International Nuclear Information System (INIS)

Yao Zhibin; He Baoping; Zhang Fengqi; Guo Hongxia; Luo Yinhong; Wang Yuanming; Zhang Keying

2009-01-01

In order to study testing methods and find sensitive parameters in total dose effects on SRAM-based FPGA, XC2S100 chips were irradiated by 60 Co γ-rays and tested with two test circuit designs. By analyzing the experimental results, the test flow of configuration RAM and bock RAM was given, and the most sensitive parameter was obtained. The results will be a solid foundation for establishing test specification and evaluation methods of total dose effects on SRAM-based FPGAs. (authors)

Synergistic effects of total ionizing dose on single event upset sensitivity in static random access memory under proton irradiation

International Nuclear Information System (INIS)

Xiao Yao; Guo Hong-Xia; Zhang Feng-Qi; Zhao Wen; Wang Yan-Ping; Zhang Ke-Ying; Ding Li-Li; Luo Yin-Hong; Wang Yuan-Ming; Fan Xue

2014-01-01

Synergistic effects of the total ionizing dose (TID) on the single event upset (SEU) sensitivity in static random access memories (SRAMs) were studied by using protons. The total dose was cumulated with high flux protons during the TID exposure, and the SEU cross section was tested with low flux protons at several cumulated dose steps. Because of the radiation-induced off-state leakage current increase of the CMOS transistors, the noise margin became asymmetric and the memory imprint effect was observed. (interdisciplinary physics and related areas of science and technology)

Treatment of carcinoma of uterine cervix with high-dose-rate intracavitary irradiation using Ralstron

International Nuclear Information System (INIS)

Suh, C.O.; Kim, G.E.; Loh, J.J.K.

1988-01-01

From May 1979 through December 1981, a total of 530 patients with carcinoma of the uterine cervix were treated with radiation therapy with curative intent. Of the 530 patients, 365 were treated with a high-dose-rate remote-controlled afterloading system (RALS) using a cobalt source, and 165 patients received a low dose rate using a radium source. External pelvic irradiation with a total of 40-50 Gy to the whole pelvis followed by intracavitary radiation (ICR) with a total dose of 30-39 Gy in ten to 13 fractions to point A was the treatment protocol. ICR was given three times a week with a dose of 3 Gy per fraction. Five-year actuarial survival rate with high-dose-rate ICR by stage was as follows: stage I:82.7% (N = 19) stage II:69.6% (N = 184), and stage III:52.2% (N = 156). The above results were comparable with those with conventional low-dose-rate ICR treatment, and late complications were far less. The application of high-dose-rate ICR was technically simple and easily performed on an outpatient basis without anesthesia, and the patients tolerated it very well. Radiation exposure to personnel was virtually none as compared with that of low-dose-rate ICR. Within a given period of time, more patients can be treated with high-dose-rate ICR because of the short treatment time. The authors therefore conclude that high-dose-rate ICR is suitable for a cancer center where a large number of patients are to be treated

Prediction of midline dose from entrance ad exit dose using OSLD measurements for total irradiation

Energy Technology Data Exchange (ETDEWEB)

Choi, Chang Heon; Park, Jong Min; Park, So Yeon; Chun, Min Soo; Han, Ji Hye; Cho, Jin Dong; Kim, Jung In [Dept. of Radiation Oncology, Seoul National University Hospital, Seoul (Korea, Republic of)

2017-06-15

This study aims to predict the midline dose based on the entrance and exit doses from optically stimulated luminescence detector (OSLD) measurements for total body irradiation (TBI). For TBI treatment, beam data sets were measured for 6 MV and 15 MV beams. To evaluate the tissue lateral effect of various thicknesses, the midline dose and peak dose were measured using a solid water phantom (SWP) and ion chamber. The entrance and exit doses were measured using OSLDs. OSLDs were attached onto the central beam axis at the entrance and exit surfaces of the phantom. The predicted midline dose was evaluated as the sum of the entrance and exit doses by OSLD measurement. The ratio of the entrance dose to the exit dose was evaluated at various thicknesses. The ratio of the peak dose to the midline dose was 1.12 for a 30 cm thick SWP at both energies. When the patient thickness is greater than 30 cm, the 15 MV should be used to ensure dose homogeneity. The ratio of the entrance dose to the exit dose was less than 1.0 for thicknesses of less than 30 cm and 40 cm at 6 MV and 15 MV, respectively. Therefore, the predicted midline dose can be underestimated for thinner body. At 15 MV, the ratios were approximately 1.06 for a thickness of 50 cm. In cases where adult patients are treated with the 15 MV photon beam, it is possible for the predicted midline dose to be overestimated for parts of the body with a thickness of 50 cm or greater. The predicted midline dose and OSLD-measured midline dose depend on the phantom thickness. For in-vivo dosimetry of TBI, the measurement dose should be corrected in order to accurately predict the midline dose.

The role of dose inhomogeneity in biological models of dose response

International Nuclear Information System (INIS)

Crawford-Brown, D.J.

1989-01-01

The paper focuses on the semi-empirical functions proposed by NAS (1980), ICRP (1977), in which terms for initiation and cell killing appear. The extent is not to produce a new model of carcinogenesis, or to reanalyse existing epidemiological data, but to explore whether an existing extrapolation function (proposed by the NAS) can be shown to have coherent theoretical support, while at the same time reproducing (however reasonably) the features of epidemiological data. Attention is restricted to irradiation by high LET radiations such as alpha particles, which may produce large inhomogeneities in both emission density and dose in cellular populations. Particular interest is directed towards epidemiological studies of uranium miners (Hornung and Meinhardt, 1987) and persons injected with 224 Ra (Spiess and Mays, 1970), although the results of the radium dial studies are included since they are discussed in the NAS report. Both populations are characterized by large uncertainties in dose estimation (mean organ dose) and by highly inhomogeneous patterns of irradiation within a single organ (Arnold and Jee, 1959; Diel, 1978; Singh, Bennettee and Wrenn, 1987; Rowland and Marshall, 1959). (author)

The effect of dose protraction on the incidence of lung carcinomas in beagle dogs with internally deposited β-emitting radionuclides

International Nuclear Information System (INIS)

Griffith, W.C.; Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Snipes, M.B.

1992-01-01

Studies using Beagle dogs were conducted to understand health effects when lung is the primary organ irradiated after inhaling insoluble radioactive particles containing one of four β-emitting radionuclides, 90 Y, 91 Y, 144 Ce, or 90 Sr. The low-LET β irradiation was delivered over a wide range of total doses and dose rate patterns that protracted the dose to lung from about 1 wk to several years. The tumor incidence rates for lung carcinomas were estimated using a proportional hazard rate model. These studies suggest that dose protraction only affects production of lung carcinomas at doses above 50 Gy

The Sandia total-dose estimator: SANDOSE description and user guide

International Nuclear Information System (INIS)

Turner, C.D.

1995-02-01

The SANdia total-DOSe Estimator (SANDOSE) is used to estimate total radiation dose to a (BRL-CAT) solid model, SANDOSE uses the mass-sectoring technique to sample the model using ray-tracing techniques. The code is integrated directly into the BRL-CAD solid model editor and is operated using a simple graphical user interface. Several diagnostic tools are available to allow the user to analyze the results. Based on limited validation using several benchmark problems, results can be expected to fall between a 10% underestimate and a factor of 2 overestimate of the actual dose predicted by rigorous radiation transport techniques. However, other situations may be encountered where the results might fall outside of this range. The code is written in C and uses X-windows graphics. It presently runs on SUN SPARCstations, but in theory could be ported to any workstation with a C compiler and X-windows. SANDOSE is available via license by contacting either the Sandia National Laboratories Technology Transfer Center or the author

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

International Nuclear Information System (INIS)

Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M.

1993-01-01

The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing 60 Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs

Relationship of dose rate and total dose to responses of continuously irradiated beagles

International Nuclear Information System (INIS)

Fritz, T.E.; Norris, W.P.; Tolle, D.V.; Seed, T.M.; Poole, C.M.; Lombard, L.S.; Doyle, D.E.

1978-01-01

Young-adult beagles were exposed continuously (22 hours/day) to 60 Co γ rays in a specially constructed facility. The exposure rates were either 5, 10, 17, or 35 R/day, and the exposures were terminated at either 600, 1400, 2000, or 4000 R. A total of 354 dogs were irradiated; 221 are still alive as long-term survivors, some after more than 2000 days. The data on survival of these dogs, coupled with data from similar preliminary experiments, allow an estimate of the LD 50 for γ-ray exposures given at a number of exposure rates. They also allow comparison of the relative importance of dose rate and total dose, and the interaction of these two variables, in the early and late effects after protracted irradiation. The LD 50 for the beagle increases from 258 rad delivered at 15 R/minute to approximately 3000 rad at 10 R/day. Over this entire range, the LD 50 is dependent upon hematopoietic damage. At 5 R/day and less, no meaningful LD 50 can be determined; there is nearly normal continued hematopoietic function, survival is prolonged, and the dogs manifest varied individual responses in other organ systems. Although the experiment is not complete, interim data allow several important conclusions. Terminated exposures, while not as effective as radiation continued until death, can produce myelogenous leukemia at the same exposure rate, 10 R/day. More importantly, at the same total accumulated dose, lower exposure rates are more damaging than higher rates on the basis of the rate and degree of hematological recovery that occurs after termination of irradiation. Thus, the rate of hematologic depression, the nadir of the depression, and the rate of recovery are dependent upon exposure rate; the latter is inversely related and the former two are directly related to exposure rate

Relationship of dose rate and total dose to responses of continuously irradiated beagles

International Nuclear Information System (INIS)

Fritz, T.E.; Norris, W.P.; Tolle, D.V.; Seed, T.M.; Poole, C.M.; Lombard, L.S.; Doyle, D.E.

1978-01-01

Young-adult beagles were exposed continuously (22 hours/day) to 60 Co gamma rays in a specially constructed facility. The exposure rates were 5, 19, 17 or 35 R/day, and the exposures were terminated at 600, 1400, 2000 or 4000 R. A total of 354 dogs were irradiated; 221 are still alive as long-term survivors, some after more than 2000 days. The data on survival of these dogs, coupled with data from similar preliminary experiments, allow an estimate of the LD 50 for gamma-ray exposures given at a number of exposure rates. They also allow comparison of the relativeimportance of dose rate and total dose, and the interaction of these two variables, in the early and late effects after protracted irradiation. The LD 50 for the beagle increases from 344 R (258 rads) delivered at 15 R/minute to approximately 4000 R (approximately 3000 rads) at 10 R/day. Over this entire range, the LD 50 is dependent upon haematopoietic damage. At 5 R/day and less, no definitive LD 50 can be determined; there is nearly normal continued haematopoietic function, survival is prolonged, and the dogs manifest varied individual responses in the organ systems. Although the experiment is not complete, interim data allow serveral important conclusions. Terminated exposures, while not as effective as irradiation continued until death, can produce myelogenous leukaemia at the same exposure rate, 10 R/day. More importantly, at the same total accumulated dose, lower exposure rates appear more damaging than higher rates on the basis of the rate and degree of haematological recovery that occurs after termination of irradiation. Thus, the rate of haematologic depression, the nadir of the depression and the rate of recovery are dependent upon exposure rate; the latter is inversely related and the first two are directly related to exposure rate. ( author)

Low-dose dual-energy cone-beam CT using a total-variation minimization algorithm

International Nuclear Information System (INIS)

Min, Jong Hwan

2011-02-01

Dual-energy cone-beam CT is an important imaging modality in diagnostic applications, and may also find its use in other application such as therapeutic image guidance. Despite of its clinical values, relatively high radiation dose of dual-energy scan may pose a challenge to its wide use. In this work, we investigated a low-dose, pre-reconstruction type of dual-energy cone-beam CT (CBCT) using a total-variation minimization algorithm for image reconstruction. An empirical dual-energy calibration method was used to prepare material-specific projection data. Raw data at high and low tube voltages are converted into a set of basis functions which can be linearly combined to produce material-specific data using the coefficients obtained through the calibration process. From much fewer views than are conventionally used, material specific images are reconstructed by use of the total-variation minimization algorithm. An experimental study was performed to demonstrate the feasibility of the proposed method using a micro-CT system. We have reconstructed images of the phantoms from only 90 projections acquired at tube voltages of 40 kVp and 90 kVp each. Aluminum-only and acryl-only images were successfully decomposed. We evaluated the quality of the reconstructed images by use of contrast-to-noise ratio and detectability. A low-dose dual-energy CBCT can be realized via the proposed method by greatly reducing the number of projections

Adaptive response of low linear energy transfer X-rays for protection against high linear energy transfer accelerated heavy ion-induced teratogenesis.

Science.gov (United States)

Wang, Bing; Ninomiya, Yasuharu; Tanaka, Kaoru; Maruyama, Kouichi; Varès, Guillaume; Eguchi-Kasai, Kiyomi; Nenoi, Mitsuru

2012-12-01

Adaptive response (AR) of low linear energy transfer (LET) irradiations for protection against teratogenesis induced by high LET irradiations is not well documented. In this study, induction of AR by X-rays against teratogenesis induced by accelerated heavy ions was examined in fetal mice. Irradiations of pregnant C57BL/6J mice were performed by delivering a priming low dose from X-rays at 0.05 or 0.30 Gy on gestation day 11 followed one day later by a challenge high dose from either X-rays or accelerated heavy ions. Monoenergetic beams of carbon, neon, silicon, and iron with the LET values of about 15, 30, 55, and 200 keV/μm, respectively, were examined. Significant suppression of teratogenic effects (fetal death, malformation of live fetuses, or low body weight) was used as the endpoint for judgment of a successful AR induction. Existence of AR induced by low-LET X-rays against teratogenic effect induced by high-LET accelerated heavy ions was demonstrated. The priming low dose of X-rays significantly reduced the occurrence of prenatal fetal death, malformation, and/or low body weight induced by the challenge high dose from either X-rays or accelerated heavy ions of carbon, neon or silicon but not iron particles. Successful AR induction appears to be a radiation quality event, depending on the LET value and/or the particle species of the challenge irradiations. These findings would provide a new insight into the study on radiation-induced AR in utero. © 2012 Wiley Periodicals, Inc.

Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

Energy Technology Data Exchange (ETDEWEB)

Yang, Tracy Chui-hsu; Craise, L.M; Prioleau, J.C.; Stampfer, M.R.; Rhim, J.S.

1990-11-01

For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude nice. Neoplastic transformation was achieved by irradiation cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level. 15 refs., 9 figs., 2 tabs.

Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

International Nuclear Information System (INIS)

Yang, Tracy Chui-hsu; Craise, L.M; Prioleau, J.C.; Stampfer, M.R.; Rhim, J.S.

1990-11-01

For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude nice. Neoplastic transformation was achieved by irradiation cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level. 15 refs., 9 figs., 2 tabs

Investigation of radial dose effect on single event upset cross-section due to heavy ions using GEANT4

International Nuclear Information System (INIS)

Boorboor, S.; Feghhi, S.A.H.; Jafari, H.

2015-01-01

The heavy ions are the main cause to produce single event upset (SEU) damage on electronic devices since they are high LET radiations. The dimension of electronic components in new technology, arise a challenge in radiation effect estimations. Accurate investigations require fully considering the ion track in energy deposition as a radial dose distribution. In this work, the distribution of delta rays as well as LET have been calculated to determine ionization structure around ion track by a Monte Carlo code, GEANT4. The radial dose of several heavy ions with different energy in silicon was investigated and compared with the works by other authors in this field. The results showed that heavy ions with identical LET can have different SEU cross-section in silicon transistors. As a demonstrative example, according to our results, the error probability for 4.8 GeV iron was 8 times greater than that for 15 MeV carbon ions, in transistors with new process technology which have small dimension and low critical charges. Our results show that considering radial dose distribution considerably improves the accuracy of the SEU cross-section estimation in electronic devices especially for new technologies. - Highlights: • The single event upset is produced by heavy ions interaction on electronic devices. • The radial dose of several heavy ions in silicon was calculated by GEANT4. • Heavy ions with identical LET had different SEU cross-section in silicon transistors. • Low dimension and critical charge devices were more sensitive to radial dose effect

Impact of total ionizing dose on the electromagnetic susceptibility of a single bipolar transistor

International Nuclear Information System (INIS)

Doridant, A.; Jarrix, S.; Raoult, J.; Blain, A.; Dusseau, L.; Chatry, N.; Calvel, P.; Hoffmann, P.

2012-01-01

Space or military electronic components are subject to both electromagnetic fields and total ionizing dose. This paper deals with the electromagnetic susceptibility of a discrete low frequency transistor subject to total ionizing dose deposition. The electromagnetic susceptibility is investigated on both non-irradiated and irradiated transistors mounted in common emitter configuration. The change in susceptibility to 100 MHz-1.5 GHz interferences lights up a synergy effect between near field electromagnetic waves and total ionizing dose. Physical mechanisms leading to changes in signal output are detailed. (authors)

Vitamin C (Vit C) added after irradiation reduces the number and alters the spectrum of CD59- mutants in human/CHO AL cells exposed to high LET carbon ions

International Nuclear Information System (INIS)

Vannais, D.B.; Hirai, Y.; Waldren, C.A.; Ueno, A.

2003-01-01

Full text: Miyazaki, Watanabe, Kumagai and colleagues discovered the existence in mammalian cells of long-lived radicals (LLR) with half-lives of minutes to hours. They further showed that concentrations of LLR were increased in a dose dependent manner by X-rays; that LLR were transforming and mutagenic but not clastogenic or lethal; that they were scavenged by Vit C but not by DMSO, and that they occured mainly (>99.8%) in proteins from which they escape by atomic tunneling. They also showed that Vit C added after radiation (but not DMSO) eliminated HPRT mutants in human cells exposed to X-rays. Following on their work, we found that Vit C (5 mM) added 30 min after radiation significantly reduced, but did not eliminate, induction of CD59- mutants in human-CHO hybrid AL cells exposed to high LET carbon beam radiation (NIRS-HIMAC, 290 MeV/nucleon, LET 100 KeV/μ: m). Lethality of the carbon beam was not affected by Vit C. DMSO decreased mutation and killing, only when present during radiation. Lycopene, reported to reduce spontaneous mutation, did not affect radiation killing or mutagenesis. Our findings with Vit C for high LET generally support the results reported for X-rays. Analysis of the spectrum of mutations in CD59- mutant cells isolated after carbon beam irradiation (2.5 Gy), indicates a substantial reduction by post-radiation Vit C in mutants with small mutations and those displaying genomic instability, seen as increased levels of translocations. Our results substantiate a role for LLR in radiation mutagenesis and implicate them in radiation-induced genomic instability

Lifetime radiation risks from low-dose rate radionuclides in beagles

International Nuclear Information System (INIS)

Goldman, M.; Rosenblatt, L.S.

1985-01-01

One of the largest, long-term (25-yr) animal studies on the effects of low-dose internal irradiation is almost completed. Some 335 beagles were given continuous exposure to graded 90 Sr [low linear energy transfer (LET)] in their diets (D-dogs) through adulthood. A second group (R-dogs) was given fractionated doses of 225 Ra (high LET) as young adults. A third group of 44 was given a single injection of 90 Sr as adults (S-dogs) to compare single to continuous dosages. All dogs were followed through their lifetimes. Only one of the 848 dogs is still alive. The animals were whole-body counted over their entire life span and were examined frequently for assessment of medical status. There were no acute radiation lethalities. Analyses of the large data base from these dogs have begun and preliminary indications are that 90 Sr, which was tested over a 1500-fold skeletal dose rate range, does not cause significant life shortening at average accumulation skeletal doses of ∼2500 rads (25 Gy) and that a curvilinear dose response curve for life shortening was seen at higher accumulation doses. The data will be discussed in terms of modern epidemiological concepts and quantifications will be related to certain parameters of human risk from acute or chronic radiation exposures

Charged particle mutagenesis at low dose and fluence in mouse splenic T cells

Energy Technology Data Exchange (ETDEWEB)

Grygoryev, Dmytro [Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239 (United States); Gauny, Stacey [Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Lasarev, Michael; Ohlrich, Anna [Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239 (United States); Kronenberg, Amy [Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Turker, Mitchell S., E-mail: turkerm@ohsu.edu [Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239 (United States); Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239 (United States)

2016-06-15

Highlights: • Densely ionizing forms of space radiation induce mutations in splenic T cells at low fluence. • Large interstitial deletions and discontinuous LOH patterns are radiation signature mutations. • Space radiation mutagenesis suggests a cancer risk from deep space travel. - Abstract: High-energy heavy charged particles (HZE ions) found in the deep space environment can significantly affect human health by inducing mutations and related cancers. To better understand the relation between HZE ion exposure and somatic mutation, we examined cell survival fraction, Aprt mutant frequencies, and the types of mutations detected for mouse splenic T cells exposed in vivo to graded doses of densely ionizing {sup 48}Ti ions (1 GeV/amu, LET = 107 keV/μm), {sup 56}Fe ions (1 GeV/amu, LET = 151 keV/μm) ions, or sparsely ionizing protons (1 GeV, LET = 0.24 keV/μm). The lowest doses for {sup 48}Ti and {sup 56}Fe ions were equivalent to a fluence of approximately 1 or 2 particle traversals per nucleus. In most cases, Aprt mutant frequencies in the irradiated mice were not significantly increased relative to the controls for any of the particles or doses tested at the pre-determined harvest time (3–5 months after irradiation). Despite the lack of increased Aprt mutant frequencies in the irradiated splenocytes, a molecular analysis centered on chromosome 8 revealed the induction of radiation signature mutations (large interstitial deletions and complex mutational patterns), with the highest levels of induction at 2 particles nucleus for the {sup 48}Ti and {sup 56}Fe ions. In total, the results show that densely ionizing HZE ions can induce characteristic mutations in splenic T cells at low fluence, and that at least a subset of radiation-induced mutant cells are stably retained despite the apparent lack of increased mutant frequencies at the time of harvest.

Revisiting Low-Dose Total Skin Electron Beam Therapy in Mycosis Fungoides

Energy Technology Data Exchange (ETDEWEB)

Harrison, Cameron, E-mail: cameronh@stanford.edu [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Young, James; Navi, Daniel [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Riaz, Nadeem [Department of Radiation Oncology, Stanford Cancer Center, Stanford, California (United States); Lingala, Bharathi; Kim, Youn [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Hoppe, Richard [Department of Radiation Oncology, Stanford Cancer Center, Stanford, California (United States)

2011-11-15

Purpose: Total skin electron beam therapy (TSEBT) is a highly effective treatment for mycosis fungoides (MF). The standard course consists of 30 to 36 Gy delivered over an 8- to 10-week period. This regimen is time intensive and associated with significant treatment-related toxicities including erythema, desquamation, anhydrosis, alopecia, and xerosis. The aim of this study was to identify a lower dose alternative while retaining a favorable efficacy profile. Methods and Materials: One hundred two MF patients were identified who had been treated with an initial course of low-dose TSEBT (5-<30 Gy) between 1958 and 1995. Patients had a T stage classification of T2 (generalized patch/plaque, n = 51), T3 (tumor, n = 29), and T4 (erythrodermic, n = 22). Those with extracutaneous disease were excluded. Results: Overall response (OR) rates (>50% improvement) were 90% among patients with T2 to T4 disease receiving 5 to <10 Gy (n = 19). In comparison, OR rates between the 10 to <20 Gy and 20 to <30 Gy subgroups were 98% and 97%, respectively. There was no significant difference in median progression free survival (PFS) in T2 and T3 patients when stratified by dose group, and PFS in each was comparable to that of the standard dose. Conclusions: OR rates associated with low-dose TSEBT in the ranges of 10 to <20 Gy and 20 to <30 Gy are comparable to that of the standard dose ({>=} 30 Gy). Efficacy measures including OS, PFS, and RFS are also favorable. Given that the efficacy profile is similar between 10 and <20 Gy and 20 and <30 Gy, the utility of TSEBT within the lower dose range of 10 to <20 Gy merits further investigation, especially in the context of combined modality treatment.

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Human health effects of low doses of ionizing radiation: the BEIR III controversy

International Nuclear Information System (INIS)

Radford, E.P.

1980-01-01

Controversy in the BEIR III Subcommittee on Somatic Effects concerning human health effects of low doses of low-LET radiation has centered on (a) the appropriate dose-response relationship by which extrapolation to low doses of data obtained at relatively high doses should be governed, and (b) the appropriate human evidence which should be the basis of estimation of lifetime cancer risk from radiation exposure. It is shown that the use of the linear no-threshold dose-response relationship for extrapolation purposes is an excellent approximation that is in agreement with widely accepted fundamental radiobiological principles. The appropriate human data for derivation of cancer risks are the composite age-specific risks derived from all epidemiologic studies of human cancer resulting from partial-body and whole-body radiation exposure; this composite is in good agreement with the currently available cancer incidence dose-response data obtained from the Nagasaki Tumor Registry. The current version of BEIR III significantly underestimates the radiation-induced cancer risk because it ignores the effect of high-dose-rate, low-LET radiation on cell survival in relation to cancer induction probability, and because it emphasizes cancer mortality rather than cancer incidence. The controversy and the way in which it was resolved raises important questions about how the public and its representatives can in the future obtain objective scientific evaluations of issues that may have significant economic, social, and political implications

Linear Energy Transfer Painting With Proton Therapy: A Means of Reducing Radiation Doses With Equivalent Clinical Effectiveness

International Nuclear Information System (INIS)

Fager, Marcus; Toma-Dasu, Iuliana; Kirk, Maura; Dolney, Derek; Diffenderfer, Eric S.; Vapiwala, Neha; Carabe, Alejandro

2015-01-01

Purpose: The purpose of this study was to propose a proton treatment planning method that trades physical dose (D) for dose-averaged linear energy transfer (LET d ) while keeping the radiobiologically weighted dose (D RBE ) to the target the same. Methods and Materials: The target is painted with LET d by using 2, 4, and 7 fields aimed at the proximal segment of the target (split target planning [STP]). As the LET d within the target increases with increasing number of fields, D decreases to maintain the D RBE the same as the conventional treatment planning method by using beams treating the full target (full target planning [FTP]). Results: The LET d increased 61% for 2-field STP (2STP) compared to FTP, 72% for 4STP, and 82% for 7STP inside the target. This increase in LET d led to a decrease of D with 5.3 ± 0.6 Gy for 2STP, 4.4 ± 0.7 Gy for 4STP, and 5.3 ± 1.1 Gy for 7STP, keeping the DRBE at 90% of the volume (DRBE, 90) constant to FTP. Conclusions: LET d painting offers a method to reduce prescribed dose at no cost to the biological effectiveness of the treatment

Linear Energy Transfer Painting With Proton Therapy: A Means of Reducing Radiation Doses With Equivalent Clinical Effectiveness

Energy Technology Data Exchange (ETDEWEB)

Fager, Marcus, E-mail: Marcus.Fager@UPHS.UPenn.edu [Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Medical Radiation Physics, Stockholm University, Stockholm (Sweden); Toma-Dasu, Iuliana [Medical Radiation Physics, Stockholm University and Karolinska Institutet, Stockholm (Sweden); Kirk, Maura; Dolney, Derek; Diffenderfer, Eric S.; Vapiwala, Neha [Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Carabe, Alejandro, E-mail: Alejandro.Carabe-Fernandez@UPHS.UPenn.edu [Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2015-04-01

Purpose: The purpose of this study was to propose a proton treatment planning method that trades physical dose (D) for dose-averaged linear energy transfer (LET{sub d}) while keeping the radiobiologically weighted dose (D{sub RBE}) to the target the same. Methods and Materials: The target is painted with LET{sub d} by using 2, 4, and 7 fields aimed at the proximal segment of the target (split target planning [STP]). As the LET{sub d} within the target increases with increasing number of fields, D decreases to maintain the D{sub RBE} the same as the conventional treatment planning method by using beams treating the full target (full target planning [FTP]). Results: The LET{sub d} increased 61% for 2-field STP (2STP) compared to FTP, 72% for 4STP, and 82% for 7STP inside the target. This increase in LET{sub d} led to a decrease of D with 5.3 ± 0.6 Gy for 2STP, 4.4 ± 0.7 Gy for 4STP, and 5.3 ± 1.1 Gy for 7STP, keeping the DRBE at 90% of the volume (DRBE, 90) constant to FTP. Conclusions: LET{sub d} painting offers a method to reduce prescribed dose at no cost to the biological effectiveness of the treatment.

LET-effects in DNA

International Nuclear Information System (INIS)

Kraft, G.; Taucher-Scholz, G.; Heilmann, J.

1994-11-01

In this contribution, an introductory view on the physical properties of ions is given and the cellular response to high LET radiation is summarized. Then the measurements of strand break induction of DNA in solution and in intracellular DNA are reported and compared to cell survival. The possibility of changes in the quality of the lesions is discussed and finally the present status of model calculations in comparison to the experiments is given. (orig./HSI)

Estimation of the total absorbed dose by quartz in retrospective conditions

International Nuclear Information System (INIS)

Correcher, V.; Delgado, A.

2003-01-01

The estimation of the total absorbed dose is of great interest in areas affected by a radiological accident when no conventional dosimetric systems are available. This paper reports about the usual methodology employed in dose reconstruction from the thermoluminescence (TL) properties of natural quartz, extracted from selected ceramic materials (12 bricks) picked up in the Chernobyl area. It has been possible to evaluate doses under 50mGy after more than 11 years later since the radiological accident happened. The main advance of this fact is the reduction of the commonly accepted limit dose estimation more than 20 times employing luminescence methods. (Author) 11 refs

A simple theory of LET spectra of heavy ion beams

International Nuclear Information System (INIS)

Wilson, J.W.; Townsend, L.W.; Schimmerling, W.; Norbury, J.W.; Wong, M.; Badavi, F.

1985-01-01

The transition of high energy ion beams through extended matter is of considerable interest to the space program as well as radiobiology and medical therapy. The transition is defined in terms of various atomic/molecular and nuclear cross sections in a Boltzmann-like equation. One dimensional solutions are derived herein from which LET spectra are derived for secondary fragments. Such LET spectra are fundamental to the evaluation of beam quality, biological effects, and radiation shield effectiveness. Sensitivity of LET spectral distributions to uncertainty in physical parameters such as the isotopic fragmentation parameters, fragment mass, and absorption cross section is established for a number of ion beams. The main limitation in LET studies is the paucity of both elemental and isotopic fragmentation data. The elemental fragmentation data is more readily available because of its simple experimental procedures. It has been suggested by some that natural abundance ratios should be used with the elemental cross sections but this leads to an order-of-magnitude error in LET spectra in many cases. Very few examples of isotopic fragmentation measurements are available. Although major advances in nuclear fragmentation theory have been made, we must await more extensive isotopic fragmentation experiments for final validation

HIGH-DOSE RATE BRACHYTHERAPY IN CARCINOMA CERVIX STAGE IIIB

Directory of Open Access Journals (Sweden)

Sathya Maruthavanan

2016-07-01

Full Text Available INTRODUCTION Radiotherapy is the standard treatment in locally advanced (IIB-IVA and early inoperable cases. The current standard of practice with curable intent is concurrent chemoradiation in which intracavitary brachytherapy is an integral component of radiotherapy. This study aims at assessing the efficacy of HDR ICBT (High-dose rate intracavitary brachytherapy in terms local response, normal tissue reactions, and feasibility. METHODS AND MATERIALS A total of 20 patients of stage IIIB cancer of the uterine cervix were enrolled in the study and were planned to receive concurrent chemotherapy weekly along with EBRT (external beam radiotherapy to a dose of 50 Gy/25 Fr. Suitability for ICBT was assessed at 40 Gy/20 Fr. 6/20 patients were suitable at 40 Gy and received HDR ICBT with a dose of 5.5 Gy to point A in 4 sessions (5.5 Gy/4 Fr. The remaining 14/20 patients completed 50 Gy and received HDR ICBT with a dose of 6 Gy to point A in 3 sessions (6 Gy/3 Fr. RESULTS A total of 66 intracavitary applications were done and only one application required dose modification due to high bladder dose, the pelvic control rate was 85% (17/20. 10% (2/20 had stable disease and 5% (1/20 had progressive disease at one year of follow up. When toxicity was considered only 15% developed grade I and grade II rectal complications. Patient compliance and acceptability was 100%. Patients were very comfortable with the short treatment time as compared with patients on LDR ICBT (low-dose rate intracavitary brachytherapy treatment interviewed during the same period. CONCLUSION This study proves that HDR brachytherapy is efficacious and feasible in carcinoma of cervix stage IIIB. It also proves that good dose distribution can be achieved with HDR intracavitary facility by the use of dose optimization. The short treatment time in HDR ICBT makes it possible to maintain this optimised dose distribution throughout the treatment providing a gain in the therapeutic ratio and

Theoretical considerations for SRAM total-dose hardening

International Nuclear Information System (INIS)

Francis, P.; Flandre, D.; Colinge, J.P.

1995-01-01

The theoretical hardness against total dose of the six-transistor SRAM cell is investigated in detail. An explicit analytical expression of the maximum tolerable threshold voltage shift is derived for two cross-coupled inverters. A numerical method is used to explore the hardness of the read and write operations. Both N- and P-channel access transistors designs are considered and their respective advantages are compared. The study points out that the radiation hardness mainly relies on the technology. Results obtained with the very robust Gate-All-Around process are finally presented

The role of radiation types and dose in induced genomic instability

International Nuclear Information System (INIS)

Kadhim Munira, A.

2007-01-01

Complete text of publication follows. Genomic Instability (GI) is defined as long-term alterations induced by low-dose exposure to a variety of genotoxic agents in mammalian cells that act to increase the 'apparent' spontaneous mutation frequency.GI is a hallmark of tumorigenic progression and is observed in the progeny of irradiated and bystander cells as the delayed and stochastic appearance of de novo chromosomal aberrations, gene mutations and delayed lethal mutations both in vitro and in vivo. It occurs at a frequency several orders of magnitude greater than would be expected for mutation in a single gene, implying that GI is a multigenic phenomenon. The expression of GI can be influenced by genotype, cell type and radiation quality; however the underlying mechanisms are not fully understood. While several studies have demonstrated GI induction by high and low LET radiation, our work on human and mouse primary cell systems has shown significant differences in the capacity to induce GI and the spectrum of alterations depending on LET. These differences might be attributed to differences in radiation track structure, radiation dose and radiation exposure regime (distribution of hit and un hit cells). In this presentation I shall review the role of radiation quality; describe the possible mechanisms underlining the observed differences between radiation type and present results of experiments demonstrating that the dose of low LET radiation might be the most significant factor in determining the role of radiation type in the induction of GI.

Liquid holding recovery kinetics in wild-type and radiosensitive mutants of the yeast Saccharomyces exposed to low- and high-LET radiations

Energy Technology Data Exchange (ETDEWEB)

Petin, Vladislav G. [Biophysical Laboratory, Medical Radiological Research Center, 249036 Obninsk (Russian Federation); Kim, Jin Kyu [Korea Atomic Energy Research Institute, 150 Deokjin-dong, Yuseong-gu, Daejeon 305-353 (Korea, Republic of)]. E-mail: jkkim@kaeri.re.kr

2005-02-15

Three wild-type diploid yeast strains Saccharomyces ellipsoideus and Saccharomyces cerevisiae and five radiosensitive mutants of S. cerevisiae in the diploid state were irradiated with {gamma}-rays from {sup 60}Co and {alpha}-particles from {sup 239}Pu in the stationary phase of growth. Survival curves and the kinetics of the liquid holding recovery were measured. It was shown that the irreversible component was enhanced for the densely ionizing radiation in comparison to the low-LET radiation while the probability of the recovery was identical for both the low- and high-LET radiations for all the strains investigated. It means that the recovery process itself is not damaged after densely ionizing radiation and the enhanced RBE of the high-LET radiation may be caused by the increased yield of the irreversible damage. A parent diploid strain and all its radiosensitive mutants showed the same probability for recovery from radiation damage. Thus, the mechanism of the enhanced radiosensitivity of the mutant cells might not be related to the damage of the repair systems themselves but with the production of some kind of radiation damage from which cells are incapable to recover.

Gamma dosimetry of high doses

International Nuclear Information System (INIS)

Martinez C, T.; Galvan G, A.; Canizal, G.

1991-01-01

The gamma dosimetry of high doses is problematic in almost all the classic dosemeters either based on the thermoluminescence, electric, chemical properties, etc., because they are saturated to very high dose and they are no longer useful. This work carries out an investigation in the interval of high doses. The solid system of heptahydrate ferrous sulfate, can be used as solid dosemeter of routine for high doses of radiation. The proposed method is simple, cheap and it doesn't require sophisticated spectrophotometers or spectrometers but expensive and not common in some laboratories

Low doses effects

International Nuclear Information System (INIS)

Tubiana, M.

1997-01-01

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

Study of total ionization dose effects in electronic devices

International Nuclear Information System (INIS)

Nidhin, T.S.; Bhattacharyya, Anindya; Gour, Aditya; Behera, R.P.; Jayanthi, T.

2018-01-01

Radiation effects in electronic devices are a major challenge in the dependable application developments of nuclear power plant instrumentation and control systems. The main radiation effects are total ionization dose (TID) effects, displacement damage dose (DDD) effects and single event effects (SEE). In this study, we are concentrating on TID effects in electronic devices. The focus of the study is mainly on SRAM based field programmable gate arrays (FPGA) along with that the devices of our interest are voltage regulators, flash memory and optocoupler. The experiments are conducted by exposing the devices to gamma radiation in power off condition and the degradation in the performances are analysed

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

Energy Technology Data Exchange (ETDEWEB)

Feinendegen, L.E

2003-07-01

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

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

International Nuclear Information System (INIS)

Feinendegen, L.E.

2003-01-01

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

Exploration of the possibility of high LET radiation for non-conventional radiotherapy in cancer

International Nuclear Information System (INIS)

1986-12-01

The report summarizes the results of the researches performed by scientists from six Member States under an Agency-sponsored co-ordinated research programme (CRP) on exploration of the possibility of high linear energy transfer (LET) radiation for non-conventional radiotherapy in cancer. The projects within the CRP were focused on radiobiological and clinical aspects of neutron beam (3 reports) and neutron capture (2 reports), heavy ion beam (2 reports) and proton (1 report) therapy. A summary report is included. A separate abstract was prepared for each of these reports

Let them eat cake!

OpenAIRE

Samson, Audrey; Gallardo, Francisco; FRAUD, -

2017-01-01

Let them eat cake!' is a food-led event serving an edible imaginary of a Facebook profile. In early 2012, Facebook conducted massive scale emotional contagion by manipulating the emotional expressions in the News Feeds of 689,003 users. This exemplifies how the governability and the biopolitics of everyday life flow through the many layers of shared images, liked videos, protocols, and hyperlinks, all orchestrated by the Facebook News Feed algorithm. 'Let them eat cake!' proposes a gustatory ...

77 FR 16566 - Submission for OMB Review, Comment Request, Proposed Collection: Let's Move Museums, Let's Move...

Science.gov (United States)

2012-03-21

..., Proposed Collection: Let's Move Museums, Let's Move Gardens AGENCY: Institute of Museum and Library..., comment request. SUMMARY: The Institute of Museum and Library Services announces that the following... functions of the agency, including whether the information will have practical utility; Evaluate the...

Implementation of high-dose chemical dosimetry for industrial facilities

International Nuclear Information System (INIS)

Conceicao, Cirilo Cezar Sant'Anna da

2006-01-01

The purpose of this work is the implementation of methodology for high dose measurements using chemical dosimeters in liquid phase, traceable to the international metrology system, and make available in the country, the standard of high-dose to industrial irradiation facilities and research irradiators, trough the quality program with comparative measurements and direct use of the standard dosimeters in routine. The use of these low cost dosimetry systems in industrial irradiation facilities, assists to the certification requirements and it can reduce the costs with dosimetry for approximately 20% of the total dosimetry costs, using these systems in routine measurements and validation process, largely substituting the imported PMMA dosimeters, among others. (author)

λ-prophage induction in E.coli cells by radiation with different LET

International Nuclear Information System (INIS)

Bonev, M.N.; Collev, S.D.

1997-01-01

λ-prophage induction in E.coli H fr H (λ) strain after irradiation with α-particles, accelerated helium ions, boron and carbon ions, as well as deuterons is investigated. The dose dependence of the fraction of induced cells is measured and its initial slope (λ-induction potency - λ i p) is determined. It is shown that the dependence of λ i p on LET is a curve with a maximum

Risk of solid cancer in low dose-rate radiation epidemiological studies and the dose-rate effectiveness factor.

Science.gov (United States)

Shore, Roy; Walsh, Linda; Azizova, Tamara; Rühm, Werner

2017-10-01

Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF). We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR Gy -1 ) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF. The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta-analyses that included only cohorts in which the mean dose was LDR data provide direct evidence regarding risk from exposures at low dose rates as an important complement to the LSS risk estimates used

Total Skin Electron Beam Therapy in the Treatment of Mycosis Fungoides: A Review of Conventional and Low-Dose Regimens.

Science.gov (United States)

Chowdhary, Mudit; Chhabra, Arpit M; Kharod, Shivam; Marwaha, Gaurav

2016-12-01

Mycosis fungoides (MF) is the most prevalent subtype of cutaneous T-cell lymphoma, which is characterized by the proliferation of CD4 + T cells. While often an indolent disease, most patients eventually develop progression from isolated patches to tumors and finally nodal or visceral involvement. Treatment choice is largely based on disease burden, though prognostic factors such as disease stage, patient age, and extracutaneous involvement must be taken into consideration. Radiotherapy represents one of the most effective therapeutic modalities in the treatment of MF. Lymphocytes are exquisitely radiosensitive, and excellent responses are observed even with low doses of radiation. Total skin electron beam therapy (TSEBT) is a special technique that allows for the homogenous irradiation of the entire skin. There are well-documented radiation dose-response relationships for achieving a complete response. As such, TSEBT doses ≥ 30 Gy comprise the current standard of care. Although highly effective, most patients experience recurrent disease even after conventional-dose (≥ 30 Gy) TSEBT. In addition, toxicity is cumulatively dose dependent, and there is reluctance to administer multiple courses of conventional-dose TSEBT. Consequently, there has been renewed interest in determining the utility of TSEBT at lower total (≤ 30 Gy) doses. Advantages of low-total-dose (with standard dose per fraction) TSEBT include a shortened treatment course, the potential to minimize the risk of adverse events, and the opportunity to allow for retreatment in cases of disease recurrence. This comprehensive review compares the impact of different TSEBT dosing schemes on clinical outcomes of MF. Copyright © 2016 Elsevier Inc. All rights reserved.

The total dose effects on the 1/f noise of deep submicron CMOS transistors

International Nuclear Information System (INIS)

Hu Rongbin; Wang Yuxin; Lu Wu

2014-01-01

Using 0.18 μm CMOS transistors, the total dose effects on the 1/f noise of deep-submicron CMOS transistors are studied for the first time in mainland China. From the experimental results and the theoretic analysis, we realize that total dose radiation causes a lot of trapped positive charges in STI (shallow trench isolation) SiO 2 layers, which induces a current leakage passage, increasing the 1/f noise power of CMOS transistors. In addition, we design some radiation-hardness structures on the CMOS transistors and the experimental results show that, until the total dose achieves 750 krad, the 1/f noise power of the radiation-hardness CMOS transistors remains unchanged, which proves our conclusion. (semiconductor devices)

Dose to red bone marrow of infants, children and adults from radiation of natural origin

Energy Technology Data Exchange (ETDEWEB)

Kendall, G M [Childhood Cancer Research Group, University of Oxford, 57 Woodstock Road, Oxford OX2 6HJ (United Kingdom); Fell, T P; Harrison, J D [Health Protection Agency, Radiation Protection Division, CRCE, Chilton, Didcot OX11 0RQ, Oxon (United Kingdom)], E-mail: Gerald.Kendall@ccrg.ox.ac.uk

2009-06-15

Natural radiation sources contribute much the largest part of the radiation exposure of the average person. This paper examines doses from natural radiation to the red bone marrow, the tissue in which leukaemia is considered to originate, with particular emphasis on doses to children. The most significant contributions are from x-rays and gamma rays, radionuclides in food and inhalation of isotopes of radon and their decay products. External radiation sources and radionuclides other than radon dominate marrow doses at all ages. The variation with age of the various components of marrow dose is considered, including doses received in utero and in each year up to the age of 15. Doses in utero include contributions resulting from the ingestion of radionuclides by the mother and placental transfer to the foetus. Postnatal doses include those from radionuclides in breast-milk and from radionuclides ingested in other foods. Doses are somewhat higher in the first year of life and there is a general slow decline from the second year of life onwards. The low linear energy transfer (LET) component of absorbed dose to the red bone marrow is much larger than the high LET component. However, because of the higher radiation weighting factor for the latter it contributes about 40% of the equivalent dose incurred up to the age of 15.

Long term results of a prospective dose escalation phase-II trial: Interstitial pulsed-dose-rate brachytherapy as boost for intermediate- and high-risk prostate cancer

International Nuclear Information System (INIS)

Lettmaier, Sebastian; Lotter, Michael; Kreppner, Stephan; Strnad, Annedore; Fietkau, Rainer; Strnad, Vratislav

2012-01-01

Purpose: We reviewed our seven year single institution experience with pulsed dose rate brachytherapy dose escalation study in patients with intermediate and high risk prostate cancer. Materials and methods: We treated a total of 130 patients for intermediate and high risk prostate cancer at our institution between 2000 and 2007 using PDR-brachytherapy as a boost after conformal external beam radiation therapy to 50.4 Gy. The majority of patients had T2 disease (T1c 6%, T2 75%, T3 19%). Seventy three patients had intermediate-risk and 53 patients had high-risk disease according to the D’Amico classification. The dose of the brachytherapy boost was escalated from 25 to 35 Gy – 33 pts. received 25 Gy (total dose 75 Gy), 63 pts. 30 Gy (total dose 80 Gy) and 34 pts. 35 Gy, (total dose 85 Gy) given in one session (dose per pulse was 0.60 Gy or 0.70 Gy/h, 24 h per day, night and day, with a time interval of 1 h between two pulses). PSA-recurrence-free survival according to Kaplan–Meier using the Phoenix definition of biochemical failure was calculated and also late toxicities according to Common Toxicity Criteria scale were assessed. Results: At the time of analysis with a median follow-up of 60 months biochemical control was achieved by 88% of patients – only 16/130 patients (12.3%) developed a biochemical relapse. Biochemical relapse free survival calculated according to Kaplan–Meier for all patients at 5 years was 85.6% (83.9% for intermediate-risk patients and 84.2% for high-risk patients) and at 9 years’ follow up it was 79.0%. Analysing biochemical relapse free survival separately for different boost dose levels, at 5 years it was 97% for the 35 Gy boost dose and 82% for the 25 and 30 Gy dose levels. The side effects of therapy were negligible: There were 18 cases (15%) of grade 1/2 rectal proctitis, one case (0.8%) of grade 3 proctitis, 18 cases (15%) of grade 1/2 cystitis, and no cases (0%) with dysuria grade 3. No patient had a bulbourethral

A clinical comparison of high dose and low dose of Suxamethonium

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RK Yadav

2014-01-01

Full Text Available Background: Suxamethonium having its rapid onset and short duration of action makes this drug unique amongst the neuromuscular blocking drugs described so far. However, use of suxamethonium is associated with a large number of undesirable side effects. Objective: To evaluate clinical effects of high and low dose of suxamethonium and to determine whether lower dose of suxamethonium can be used for any beneficial effects in terms of its various adverse effects e.g. cardiovascular responses, post-operative muscle pains and intraocular pressure. Methods: A total of 100 patients were included in this prospective study. All these patients on preoperative clinical evaluation were assessed to have adequate airway. All the patients were divided in two groups, low dose group (group I and High dose group (group II with 50 patients in each at random. A standard anesthetic technique was adhered to all the patients and following parameters were observed on comparative basis: a. Fasciculation and post operative myalgia. b. Cardiovascular effects, c. Intraocular pressure. Observation: The incidence of post Suxamethonium pain was significantly greater in group II. Increase in heart rate from baseline was significant in both groups. There was no significant difference between the two groups in the diastolic pressure but rise in systolic blood pressure was significant at all assessment times in both groups. This rise from control was statistically significant. Conclusion: Suxamethonium can be used in lower doses (0.5 mg/kg in elective cases without airway compromise. It gives benefits of reduced muscle pains, cardiovascular responses and intraocular hypertension. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-2, 1-8 DOI: http://dx.doi.org/10.3126/jcmsn.v9i2.9677

Effect of LET on the efficiency of dose re-estimation in LiF using uv photo-transfer

Energy Technology Data Exchange (ETDEWEB)

Douglas, J A; Baker, D M; Marshall, M; Budd, T [UKAEA Atomic Energy Research Establishment, Harwell. Environmental and Medical Sciences Div.

1980-09-01

Glow curves from TLD600 and TLD700 extruded rods exposed to ..gamma..-, X- and neutron radiations have been compared before and after uv photo-transfer. Re-estimation efficiency increases with LET by an amount which varies from batch to batch.

3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation.

Science.gov (United States)

Hagiwara, Yoshihiko; Niimi, Atsuko; Isono, Mayu; Yamauchi, Motohiro; Yasuhara, Takaaki; Limsirichaikul, Siripan; Oike, Takahiro; Sato, Hiro; Held, Kathryn D; Nakano, Takashi; Shibata, Atsushi

2017-12-12

DNA double-strand breaks (DSBs) induced by ionising radiation are considered the major cause of genotoxic mutations and cell death. While DSBs are dispersed throughout chromatin after X-rays or γ-irradiation, multiple types of DNA damage including DSBs, single-strand breaks and base damage can be generated within 1-2 helical DNA turns, defined as a complex DNA lesion, after high Linear Energy Transfer (LET) particle irradiation. In addition to the formation of complex DNA lesions, recent evidence suggests that multiple DSBs can be closely generated along the tracks of high LET particle irradiation. Herein, by using three dimensional (3D)-structured illumination microscopy, we identified the formation of 3D widespread γH2AX foci after high LET carbon-ion irradiation. The large γH2AX foci in G 2 -phase cells encompassed multiple foci of replication protein A (RPA), a marker of DSBs undergoing resection during homologous recombination. Furthermore, we demonstrated by 3D analysis that the distance between two individual RPA foci within γH2AX foci was approximately 700 nm. Together, our findings suggest that high LET heavy-ion particles induce clustered DSB formation on a scale of approximately 1 μm 3 . These closely localised DSBs are considered to be a risk for the formation of chromosomal rearrangement after heavy-ion irradiation.

High-dose ascorbic acid decreases cholesterolemic factors of an atherogenic diet in guinea pigs.

Science.gov (United States)

Filis, Konstantinos; Anastassopoulou, Aikaterini; Sigala, Fragiska; Theodorou, Dimitrios; Manouras, Andreas; Leandros, Emanouel; Sigalas, Panagiotis; Hepp, Wolfgang; Bramis, John

2007-03-01

The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

Design of spray dried insulin microparticles to bypass deposition in the extrathoracic region and maximize total lung dose.

Science.gov (United States)

Ung, Keith T; Rao, Nagaraja; Weers, Jeffry G; Huang, Daniel; Chan, Hak-Kim

2016-09-25

Inhaled drugs all too often deliver only a fraction of the emitted dose to the target lung site due to deposition in the extrathoracic region (i.e., mouth and throat), which can lead to increased variation in lung exposure, and in some instances increases in local and systemic side effects. For aerosol medications, improved targeting to the lungs may be achieved by tailoring the micromeritic properties of the particles (e.g., size, density, rugosity) to minimize deposition in the mouth-throat and maximize the total lung dose. This study evaluated a co-solvent spray drying approach to modulate particle morphology and dose delivery characteristics of engineered powder formulations of insulin microparticles. The binary co-solvent system studied included water as the primary solvent mixed with an organic co-solvent, e.g., ethanol. Factors such as the relative rate of evaporation of each component of a binary co-solvent mixture, and insulin solubility in each component were considered in selecting feedstock compositions. A water-ethanol co-solvent mixture with a composition range considered suitable for modulating particle shell formation during drying was selected for experimental investigation. An Alberta Idealized Throat model was used to evaluate the in vitro total lung dose of a series of spray dried insulin formulations engineered with different bulk powder properties and delivered with two prototype inhalers that fluidize and disperse powder using different principles. The in vitro total lung dose of insulin microparticles was improved and favored for powders with low bulk density and small primary particle size, with reduction of deposition in the extrathoracic region. The results demonstrated that a total lung dose >95% of the delivered dose can be achieved with engineered particles, indicating a high degree of lung targeting, almost completely bypassing deposition in the mouth-throat. Copyright © 2016 Elsevier B.V. All rights reserved.

Preservation of Minced Meats by Using Medium and High-doses Irradiation

International Nuclear Information System (INIS)

Hammad, A.A.I.; Swailam, H.M.H.; Taha, S.M.A.

2003-01-01

The effect of medium (2.5-10 kGy) dose irradiation and high(20-70 kGy) dose irradiation on the microbiological, chemical and organoleptic properties of minced meat samples was studied. It was found that irradiation dose of only 5 kGy greatly reduced all microbial counts and completely eliminated all non-spore forming pathogenic bacteria contaminated minced meat samples. Consequently this irradiation dose extended the refrigerated (3 degree ±1) storage life of these products for more than 8 weeks. This irradiation dose almost did not affect the chemical composition, particularly the main amino acids and main fatty acids of minced meat samples. Panelists could not differentiate between irradiated minced meat samples at this dose and unirradiated samples. High doses irradiation, i.e.40 and 70 kGy were sufficient and efficient in sterilization of minced meat samples and in obtaining long-stable minced meat products (Two years) at ambient temperature. These irradiation doses slightly reduced (not more than 7%) aspartic acid, glutamic acid, methionine and lysine of minced meat. It also decreased the relative percentage of total unsaturated fatty acids by not more than 17 % . These high irradiation doses caused loss of C 18:3 and C 20:1

Totality eclipses of the Sun

CERN Document Server

Littmann, Mark; Willcox, Ken

2008-01-01

A total eclipse of the Sun is the most awesome sight in the heavens. Totality: Eclipses of the Sun takes you to eclipses of the past, present, and future, and lets you see - and feel - why people travel to the ends of the Earth to observe them. - ;A total eclipse of the Sun is the most awesome sight in the heavens. Totality: Eclipses of the Sun takes you to eclipses of the past, present, and future, and lets you see - and feel - why people travel to the ends of the Earth to observe them. Totality: Eclipses of the Sun is the best guide and reference book on solar eclipses ever written. It explains: how to observe them; how to photograph and videotape them; why they occur; their history and mythology; and future eclipses - when and where to see them. Totality also tells the remarkable story of how eclipses shocked scientists, revealed the workings of the Sun, and made Einstein famous. And the book shares the experiences and advice of many veteran eclipse observers. Totality: Eclipses of the Sun is profusely ill...

Serum protein concentration in low-dose total body irradiation of normal and malnourished rats

International Nuclear Information System (INIS)

Viana, W.C.M.; Lambertz, D.; Borges, E.S.; Neto, A.M.O.; Lambertz, K.M.F.T.; Amaral, A.

2016-01-01

Among the radiotherapeutics' modalities, total body irradiation (TBI) is used as treatment for certain hematological, oncological and immunological diseases. The aim of this study was to evaluate the long-term effects of low-dose TBI on plasma concentration of total protein and albumin using prematurely and undernourished rats as animal model. For this, four groups with 9 animals each were formed: Normal nourished (N); Malnourished (M); Irradiated Normal nourished (IN); Irradiated Malnourished (IM). At the age of 28 days, rats of the IN and IM groups underwent total body gamma irradiation with a source of cobalt-60. Total protein and Albumin in the blood serum was quantified by colorimetry. This research indicates that procedures involving low-dose total body irradiation in children have repercussions in the reduction in body-mass as well as in the plasma levels of total protein and albumin. Our findings reinforce the periodic monitoring of total serum protein and albumin levels as an important tool in long-term follow-up of pediatric patients in treatments associated to total body irradiation. - Highlights: • Low-dose total body irradiation (TBI) in children have repercussions in their body-mass. • Long-term total protein and albumin levels are affected by TBI. • The monitoring of total protein and albumin levels are useful in the follow-up of TBI pediatric patients.

Worst-Case Bias During Total Dose Irradiation of SOI Transistors

International Nuclear Information System (INIS)

Ferlet-Cavrois, V.; Colladant, T.; Paillet, P.; Leray, J.-L; Musseau, O.; Schwank, James R.; Shaneyfelt, Marty R.; Pelloie, J.L.; Du Port de Poncharra, J.

2000-01-01

The worst case bias during total dose irradiation of partially depleted SOI transistors (from SNL and from CEA/LETI) is correlated to the device architecture. Experiments and simulations are used to analyze SOI back transistor threshold voltage shift and charge trapping in the buried oxide

The carcinogenic risks of low-LET and high-LET ionizing radiations

International Nuclear Information System (INIS)

Fabrikant, J.I.

1989-08-01

New information is available concerning the carcinogenic effects of radiation and the implications for risk assessment and risk management. This information comes from further follow-up of the epidemiological studies of the Japanese atomic bomb survivors, patients irradiated medically for cancer and allied conditions, and workers exposed in various occupations. In the Japanese atomic bomb survivors the carcinogenic risks are estimated to be somewhat higher than previously, due to the reassessment of the atomic-bomb dosimetry, further follow-up with increase in the number of excess cancer deaths, particularly in survivors irradiated early in life, and changes in the methods of analysis to compute the age-specific risks of cancer. Because of the characteristics of the atomic bomb survivor series as regards sample size, age and sex distribution, duration for follow-up, person-years at risk, and type of dosimetry, the mortality experience of the atomic bomb survivors was selected by the UNSCEAR Committee and the BEIR V Committee as the more appropriate basis for projecting risk estimates for the general population. In the atomic bomb survivors, the dose-effect relationship for overall cancer mortality other than leukemia is consistent with linearity below 3 Gy, while the dose-effect relationship for leukemia, excluding chronic lymphatic leukemia, conforms best to a linear-quadratic function. The shape of the dose-incidence curve at low doses still remains uncertain, and the data do not rule out the possible existence of a threshold for an neoplasm. The excess relative risk of mortality from all cancers combined is estimated to be 1.39 per Gy (shielded kerma), which corresponds to an absolute risk of 10.0 excess cancer deaths per 10,000 PYGy; the relative risks is 1.41 at 1 Gy (organ-absorbed dose), and an absolute risk of 13.07 excess cancer deaths per 10,000 PYGy. 19 refs

Immune reactivity after high-dose irradiation

International Nuclear Information System (INIS)

Gassmann, W.; Wottge, H.U.; von Kolzynski, M.; Mueller-Ruchholtz, W.

1986-01-01

Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient

Interaction of 2-Gy Equivalent Dose and Margin Status in Perioperative High-Dose-Rate Brachytherapy

International Nuclear Information System (INIS)

Martinez-Monge, Rafael; Cambeiro, Mauricio; Moreno, Marta; Gaztanaga, Miren; San Julian, Mikel; Alcalde, Juan; Jurado, Matias

2011-01-01

Purpose: To determine patient, tumor, and treatment factors predictive of local control (LC) in a series of patients treated with either perioperative high-dose-rate brachytherapy (PHDRB) alone (Group 1) or with PHDRB combined with external-beam radiotherapy (EBRT) (Group 2). Patient and Methods: Patients (n = 312) enrolled in several PHDRB prospective Phase I-II studies conducted at the Clinica Universidad de Navarra were analyzed. Treatment with PHDRB alone, mainly because of prior irradiation, was used in 126 patients to total doses of 32 Gy/8 b.i.d. or 40 Gy/10 b.i.d. treatments after R0 or R1 resections. Treatment with PHDRB plus EBRT was used in 186 patients to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments after R0 or R1 resections along with 45 Gy of EBRT with or without concomitant chemotherapy. Results: No dose-margin interaction was observed in Group 1 patients. In Group 2 patients there was a significant interaction between margin status and 2-Gy equivalent (Eq2Gy) dose (p = 0.002): (1) patients with negative margins had 9-year LC of 95.7% at Eq2Gy = 62.9Gy; (2) patients with close margins of >1 mm had 9-year LC of 92.4% at Eq2Gy = 72.2Gy, and (3) patients with positive/close <1-mm margins had 9-year LC of 68.0% at Eq2Gy = 72.2Gy. Conclusions: Two-gray equivalent doses ≥70 Gy may compensate the effect of close margins ≥1 mm but do not counterbalance the detrimental effect of unfavorable (positive/close <1 mm) resection margins. No dose-margin interaction is observed in patients treated at lower Eq2Gy doses ≤50 Gy with PHDRB alone.

Biologically effective dose in total-body irradiation and hematopoietic stem cell transplantation

International Nuclear Information System (INIS)

Kal, H.B.; Kempen-Harteveld, M.L. van; Heijenbrok-Kal, M.H.; Struikmans, H.

2006-01-01

Background and Purpose: Total-body irradiation (TBI) is an important part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. The results after treatment with various TBI regimes were compared, and dose-effect relationships for the endpoints relapse incidence, disease-free survival, treatment-related mortality, and overall survival were derived. The aim was to define requirements for an optimal treatment schedule with respect to leukemic cell kill and late normal-tissue morbidity. Material and Methods: A literature search was performed. Three randomized studies, four studies comparing results of two or three TBI regimens, and nine reports with results of one specific TBI regimen were identified. Biologically effective doses (BEDs) were calculated. The results of the randomized studies and the studies comparing results of two or three TBI regimens were pooled, and the pooled relative risk (RR) was calculated for the treatments with high BED values versus treatments with a low BED. BED-effect relationships were obtained. Results: RRs for the high BED treatments were significantly lower for relapse incidence, not significantly different for disease-free survival and treatment-related mortality, and significantly higher for overall survival. BED-effect relationships indicate a decrease in relapse incidence and treatment-related mortality and an increase in disease-free and overall survival with higher BED values. Conclusion: 'More dose is better', provided that a TBI setting is used limiting the BEDs of lungs, kidneys, and eye lenses. (orig.)

Low level dose induced chromosome aberrations in human blood lymphocytes

International Nuclear Information System (INIS)

Pohl-Rueling, J.

1992-01-01

Unstable structural aberrations in chromosomes of human blood lymphocytes cannot be used as biological dosemeters in the low dose range, when extrapolating from high doses using a linear dose response, as required by the original formula of the dual radiation action theory. A survey is given of experimental dose-response curves of chromosome aberrations, obtained in investigations not only by this institute, in cooperation with many other laboratories, but also by various authors in different areas of the world. The results are not compatible with the predicted linear dose relationships at in vivo dose ranges up to 30 mGy.y -1 . The aberration frequencies rise sharply with dose within the normal environmental exposure up to about twice that level. At higher doses, aberration frequencies increase less rapidly and reach a plateau. Some in vitro experiments of various authors with higher doses of low LET radiations, up to about 400 mGy have found dose responses with steps. (author)

Estimation of the dose distribution within, and total dose to, the body of an acutely overexposed person

International Nuclear Information System (INIS)

Beer, G.P. de; Feather, J.I.; Oude, A. de; Language, A.E.

1981-01-01

In a case of accidental overexposure of a person, it is important to obtain a reliable value of the whole body dose as well as of the dose distribution within the body. Any follow-up treatment based only on the clinical effects as and when they appear, may result in insufficient or even erroneous therapy. In this respect knowledge of total dose and its distribution within the body may be a valuable aid in deciding on the follow-up treatment, taking into account the latent nature of the clinical effects. The calculated whole body dose and its distribution within the body of a person overexposed to a 192 Ir radiography source, are compared to experimentally determined values. In both cases the calculated values prove to be of sufficient accuracy to serve as an aid in decisions on the follow-up treatment. (author)

Analysis of Chromosomal Aberrations after Low and High Dose Rate Gamma Irradiation in ATM or NBS Suppressed Human Fibroblast Cells

Science.gov (United States)

Hada, M.; Huff, J. L.; Patel, Z.; Pluth, J. M.; George, K. A.; Cucinotta, F. A.

2009-01-01

A detailed understanding of the biological effects of heavy nuclei is needed for space radiation protection and for cancer therapy. High-LET radiation produces more complex DNA lesions that may be non-repairable or that may require additional processing steps compared to endogenous DSBs, increasing the possibility of misrepair. Interplay between radiation sensitivity, dose, and radiation quality has not been studied extensively. Previously we studied chromosome aberrations induced by low- and high- LET radiation in several cell lines deficient in ATM (ataxia telangactasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. We found that the yields of both simple and complex chromosomal aberrations were significantly increased in the DSB repair defective cells compared to normal cells. The increased aberrations observed for the ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher in NBS cells only for simple exchanges. These results point to the importance of the functions of ATM and NBS in chromatin modifications that function to facilitate correct DSB repair and minimize aberration formation. To further understand the sensitivity differences that were observed in ATM and NBS deficient cells, in this study, chromosomal aberration analysis was performed in normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, or Mirin, an MRN complex inhibitor involved in activation of ATM. We are also testing siRNA knockdown of these proteins. Normal and ATM or NBS suppressed cells were irradiated with gamma-rays and chromosomes were collected with a premature chromosome

Biological dose estimation for accidental supra-high dose gamma-ray exposure

International Nuclear Information System (INIS)

Chen, Y.; Yan, X.K.; Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K.

2011-01-01

To correctly estimate the biological dose of victims accidentally exposed to a very high dose of 60 Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of 60 Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0 -3 D 2 . Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy γ-irradiation from a supra-high dose 60 Co gamma-ray accident.

High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth

International Nuclear Information System (INIS)

Inoue, Takehiro; Inoue, Toshihiko; Yamazaki, Hideya; Koizumi, Masahiko; Kagawa, Kazufumi; Yoshida, Ken; Shiomi, Hiroya; Imai, Atsushi; Shimizutani, Kimishige; Tanaka, Eichii; Nose, Takayuki; Teshima, Teruki; Furukawa, Souhei; Fuchihata, Hajime

1998-01-01

Purpose: Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth. Methods and Materials: From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using 198 Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. Results: Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with 198 Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR. Conclusion: HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff

Time- and radiation-dose dependent changes in the plasma proteome after total body irradiation of non-human primates: Implications for biomarker selection.

Directory of Open Access Journals (Sweden)

Stephanie D Byrum

Full Text Available Acute radiation syndrome (ARS is a complex multi-organ disease resulting from total body exposure to high doses of radiation. Individuals can be exposed to total body irradiation (TBI in a number of ways, including terrorist radiological weapons or nuclear accidents. In order to determine whether an individual has been exposed to high doses of radiation and needs countermeasure treatment, robust biomarkers are needed to estimate radiation exposure from biospecimens such as blood or urine. In order to identity such candidate biomarkers of radiation exposure, high-resolution proteomics was used to analyze plasma from non-human primates following whole body irradiation (Co-60 at 6.7 Gy and 7.4 Gy with a twelve day observation period. A total of 663 proteins were evaluated from the plasma proteome analysis. A panel of plasma proteins with characteristic time- and dose-dependent changes was identified. In addition to the plasma proteomics study reported here, we recently identified candidate biomarkers using urine from these same non-human primates. From the proteomic analysis of both plasma and urine, we identified ten overlapping proteins that significantly differentiate both time and dose variables. These shared plasma and urine proteins represent optimal candidate biomarkers of radiation exposure.

Experimental data and dose-response models

International Nuclear Information System (INIS)

Ullrich, R.L.

1985-01-01

Dose-response relationships for radiation carcinogenesis have been of interest to biologists, modelers, and statisticians for many years. Despite his interest there are few instances in which there are sufficient experimental data to allow the fitting of various dose-response models. In those experimental systems for which data are available the dose-response curves for tumor induction for the various systems cannot be described by a single model. Dose-response models which have been observed following acute exposures to gamma rays include threshold, quadratic, and linear models. Data on sex, age, and environmental influences of dose suggest a strong role of host factors on the dose response. With decreasing dose rate the effectiveness of gamma ray irradiation tends to decrease in essentially every instance. In those cases in which the high dose rate dose response could be described by a quadratic model, the effect of dose rate is consistent with predictions based on radiation effects on the induction of initial events. Whether the underlying reasons for the observed dose-rate effect is a result of effects on the induction of initial events or is due to effects on the subsequent steps in the carcinogenic process is unknown. Information on the dose response for tumor induction for high LET (linear energy transfer) radiations such as neutrons is even more limited. The observed dose and dose rate data for tumor induction following neutron exposure are complex and do not appear to be consistent with predictions based on models for the induction of initial events

Total body irradiation

International Nuclear Information System (INIS)

Novack, D.H.; Kiley, J.P.

1987-01-01

The multitude of papers and conferences in recent years on the use of very large megavoltage radiation fields indicates an increased interest in total body, hemibody, and total nodal radiotherapy for various clinical situations. These include high dose total body irradiation (TBI) to destroy the bone marrow and leukemic cells and provide immunosuppression prior to a bone marrow transplant, high dose total lymphoid irradiation (TLI) prior to bone marrow transplantation in severe aplastic anemia, low dose TBI in the treatment of lymphocytic leukemias or lymphomas, and hemibody irradiation (HBI) in the treatment of advanced multiple myeloma. Although accurate provision of a specific dose and the desired degree of dose homogeneity are two of the physicist's major considerations for all radiotherapy techniques, these tasks are even more demanding for large field radiotherapy. Because most large field radiotherapy is done at an extended distance for complex patient geometries, basic dosimetry data measured at the standard distance (isocenter) must be verified or supplemented. This paper discusses some of the special dosimetric problems of large field radiotherapy, with specific examples given of the dosimetry of the TBI program for bone marrow transplant at the authors' hospital

Influence of dose and its distribution in time on dose-response relationships for low-LET radiation

International Nuclear Information System (INIS)

Anon.

1980-01-01

This book examines the influence of dose rate and magnitude on the genetic and carcinogenic effects of radiation exposure in animals and man. It systematically examines a broad range of biological effects in simple systems, plants, laboratory animals, and man with special attention given to the effects of prenatal irradiation, changes in life span, and tumorigenesis. An enormous volume of data is provided about human tumorigenesis and the data and shortcomings are summarized. There is an extended general discussion of the consideration in quantitative dose and dose rate relationships and of the limitations of the data and analyses which have led to a linear interpolation of risk at low doses and dose rates. An argument is made for dose rate dependence in tumorigenesis as being consistent with all other radiation effects and for the applicability of Dose Rate Effectiveness Factors (DREF) in providing a more realistic assessment of the risk of radiation carcinogenesis. The report is documented with 24 pages of references. There are numerous graphs and tables, all clear and to the point. This book is a superb review and summary of the data on radiation risks

Transperineal high-dose-rate interstitial radiation therapy in the management of gynecologic malignancies

Energy Technology Data Exchange (ETDEWEB)

Itami, Jun; Hara, Ryuseke; Kozuka, Takuyou; Yamashita, Hideomi; Nakajima, Kaori; Shibata, Kouji; Abe, Yoshihisa; Fuse, Masashi; Ito, Masashi [International Medical Center of Japan, Tokyo (Japan). Dept. of Radiation Therapy and Oncology

2003-11-01

Background: High-dose-rate interstitial radiation therapy is a newly introduced modality, and its role in the management of gynecologic malignancies remains to be studied. Clinical experience in high-dose-rate interstitial radiation therapy was retrospectively investigated. Patients and Methods: Eight patients with primary and nine with recurrent gynecologic malignancies underwent high-dose-rate interstitial radiation therapy with/without external-beam irradiation. Fractional dose of the high-dose-rate interstitial radiation therapy ranged between 4 and 6 Gy with total doses of 15-54 Gy. Interstitial irradiation was performed twice daily with an interval of > 6 h. Results: 2-year local control rate was 75% for primary treatment and 47% for treatment of recurrence (p = 0.46). Maximum tumor size had a statistically significant impact on local control (p < 0.002). Grade 2 and 4 late complications were seen in five patients, and the incidence was significantly higher in patients with a larger volume enclosed by the prescribed fractional dose of high-dose-rate interstitial radiation therapy. The incidence of grade 2 and 4 complications at 18 months was 78% and 0% with a volume > 100 cm{sup 3} and {<=} 100 cm{sup 3}, respectively (p < 0.04). Conclusion: Although high-dose-rate interstitial radiation therapy is a promising modality, it must be applied cautiously to patients with bulky tumors because of the high incidence of serious complications. (orig.)

Evaluation of Total Daily Dose and Glycemic Control for Patients on U-500 Insulin Admitted to the Hospital

Science.gov (United States)

2016-05-20

regular insulin has significantly increased in recent years. These patients are severely insulin resistant requiring high doses of insulin to achieve...on U-500 Insulin Admitted to the Hospital presented at SURF Conference, San Antonio, TX 20 May 201 6 with MDWI 41-108, and has been assigned local...59th CSPG/SGVU) C.201 4 . I 52d PROTOCOL TITLE Evaluation of Total Dai ly Dose and Glycemic Control for Patients on U-500 Insulin Admitted to the

An Approach to Energy Education for High School, Junior High School and Elementary School Students at Aichi Institute of Technology

Science.gov (United States)

Yukita, Kazuto; Ichiyanagi, Katsuhiro; Mori, Tsuyoshi; Goto, Yasuyuki

This paper discusses the methods of implementation and improvement adopted in the energy education program of “Marugoto Taiken World” (“Total Experience World”) at Aichi Institute of Technology. The program, which is aimed at high school, junior high school and elementary school students, has been carried on at Aichi Institute of Technology for a number of years now, and the authors have been involved in the energy education project for the past four years. During that time, the following four courses have been held : 1) Let's use wind power to generate electricity, 2) Let's use flowers to build a solar battery, 3) Let's use bottles to build a fuel cell battery, 4) Let's make all sorts of batteries.

Neutron dose to patients treated with high-energy medical accelerators

International Nuclear Information System (INIS)

McGinley, P.H.

2001-01-01

The neutron dose equivalent received by patients treated with high energy x-ray beams was measured in this research. A total of 13 different medical accelerators were evaluated in terms of the neutron dose equivalent in the patient plane and at the beam center. The neutron dose equivalent at the beam center was found to ranged from 0.02 to 9.4 mSv per Sv of x-ray dose and values from 0.029 to 2.58 mSv per Sv of x-ray were measured in the patient plane. It was concluded that the neutron levels meet the International Electrotechnical Commission standard for the patient plane. It was also concluded that when intensity modulated radiation treatment is conducted the neutron dose equivalent received by the patient will increase by a factor of 2 to 10. (author)

Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

International Nuclear Information System (INIS)

Renis, M.; Malfa, G.; Tomasello, B.; Borghesi, M.; Schettino, G.; Favetta, M.; Romano, F.; Cirrone, G. A. P.; Manti, L.

2013-01-01

Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/μm on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately

Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

Energy Technology Data Exchange (ETDEWEB)

Renis, M.; Malfa, G.; Tomasello, B. [Drug Sciences Department, University of Catania, Catania (Italy); Borghesi, M.; Schettino, G. [Queen' s University Belfast, Northern Ireland (United Kingdom); Favetta, M.; Romano, F.; Cirrone, G. A. P. [National Institute for Nuclear Physics (INFN-LNS), Catania (Italy); Manti, L. [Physics Science Department, University of Naples Federico II, Naples, and National Institute for Nuclear Physics (INFN), Naples (Italy)

2013-07-26

Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/μm on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately

TU-F-CAMPUS-T-01: Dose and Energy Spectra From Neutron Induced Radioactivity in Medical Linear Accelerators Following High Energy Total Body Irradiation

International Nuclear Information System (INIS)

Keehan, S; Taylor, M; Franich, R; Smith, R; Dunn, L; Kron, T

2015-01-01

Purpose: To assess the risk posed by neutron induced activation of components in medical linear accelerators (linacs) following the delivery of high monitor unit 18 MV photon beams such as used in TBI. Methods: Gamma spectroscopy was used to identify radioisotopes produced in components of a Varian 21EX and an Elekta Synergy following delivery of photon beams. Dose and risk estimates for TBI were assessed using dose deliveries from an actual patient treatment. A 1 litre spherical ion chamber (PTW, Germany) has been used to measure the dose at the beam exit window and at the total body irradiation (TBI) treatment couch following large and small field beams with long beam-on times. Measurements were also made outside of the closed jaws to quantify the benefit of the attenuation provided by the jaws. Results: The radioisotopes produced in the linac head have been identified as 187 W, 56 Mn, 24 Na and 28 Al, which have half-lives from between 2.3 min to 24 hours. The dose at the beam exit window following an 18 MV 2197 MU TBI beam delivery was 12.6 µSv in ten minutes. The dose rate at the TBI treatment couch 4.8 m away is a factor of ten lower. For a typical TBI delivered in six fractions each consisting of four beams and an annual patient load of 24, the annual dose estimate for a staff member at the treatment couch for ten minutes is 750 µSv. This can be further reduced by a factor of about twelve if the jaws are closed before entering the room, resulting in a dose estimate of 65 µSv. Conclusion: The dose resulting from the activation products for a representative TBI workload at our clinic of 24 patients per year is 750 µSv, which can be further reduced to 65 µSv by closing the jaws

Estimation of the total effective dose from low-dose CT scans and radiopharmaceutical administrations delivered to patients undergoing SPECT/CT explorations

International Nuclear Information System (INIS)

Montes, C.; Hernandez, J.; Gomez-Caminero, F.; Garcia, S.; Martin, C.; Rosero, A.; Tamayo, P.

2013-01-01

Hybrid imaging, such as single photon emission computed tomography (SPECT)/CT, is used in routine clinical practice, allowing coregistered images of the functional and structural information provided by the two imaging modalities. However, this multimodality imaging may mean that patients are exposed to a higher radiation dose than those receiving SPECT alone. The study aimed to determine the radiation exposure of patients who had undergone SPECT/CT examinations and to relate this to the Background Equivalent Radiation Time (BERT). 145 SPECT/CT studies were used to estimate the total effective dose to patients due to both radiopharmaceutical administrations and low-dose CT scans. The CT contribution was estimated by the Dose-Length Product method. Specific conversion coefficients were calculated for SPECT explorations. The radiation dose from low-dose CTs ranged between 0.6 mSv for head and neck CT and 2.6 mSv for whole body CT scan, representing a maximum of 1 year of background radiation exposure. These values represent a decrease of 80-85% with respect to the radiation dose from diagnostic CT. The radiation exposure from radiopharmaceutical administration varied from 2.1 mSv for stress myocardial perfusion SPECT to 26 mSv for gallium SPECT in patients with lymphoma. The BERT ranged from 1 to 11 years. The contribution of low-dose CT scans to the total radiation dose to patients undergoing SPECT/CT examinations is relatively low compared with the effective dose from radiopharmaceutical administration. When a CT scan is only acquired for anatomical localization and attenuation correction, low-dose CT scan is justified on the basis of its lower dose. (author)

Let-7 microRNAs are developmentally regulated in circulating human erythroid cells

Directory of Open Access Journals (Sweden)

Reed Christopher

2009-11-01

Full Text Available Abstract Background MicroRNAs are ~22nt-long small non-coding RNAs that negatively regulate protein expression through mRNA degradation or translational repression in eukaryotic cells. Based upon their importance in regulating development and terminal differentiation in model systems, erythrocyte microRNA profiles were examined at birth and in adults to determine if changes in their abundance coincide with the developmental phenomenon of hemoglobin switching. Methods Expression profiling of microRNA was performed using total RNA from four adult peripheral blood samples compared to four cord blood samples after depletion of plasma, platelets, and nucleated cells. Labeled RNAs were hybridized to custom spotted arrays containing 474 human microRNA species (miRBase release 9.1. Total RNA from Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines provided a hybridization reference for all samples to generate microRNA abundance profile for each sample. Results Among 206 detected miRNAs, 79% of the microRNAs were present at equivalent levels in both cord and adult cells. By comparison, 37 microRNAs were up-regulated and 4 microRNAs were down-regulated in adult erythroid cells (fold change > 2; p let-7 miRNA family consistently demonstrated increased abundance in the adult samples by array-based analyses that were confirmed by quantitative PCR (4.5 to 18.4 fold increases in 6 of 8 let-7 miRNA. Profiling studies of messenger RNA (mRNA in these cells additionally demonstrated down-regulation of ten let-7 target genes in the adult cells. Conclusion These data suggest that a consistent pattern of up-regulation among let-7 miRNA in circulating erythroid cells occurs in association with hemoglobin switching during the fetal-to-adult developmental transition in humans.

The relationships between RBE and LET for different types of lethal damage in mammalian cells: biophysical and molecular mechanisms

NARCIS (Netherlands)

Barendsen, G. W.

1994-01-01

The relative biological effectiveness (RBE) of radiations as a function of linear energy transfer (LET) is analyzed for different types of damage causing reproductive death of mammalian cells. Survival curves are evaluated assuming a linear-quadratic dose dependence of the induction of reproductive

Development of Real-Time Measurement of Effective Dose for High Dose Rate Neutron Fields

CERN Document Server

Braby, L A; Reece, W D

2003-01-01

Studies of the effects of low doses of ionizing radiation require sources of radiation which are well characterized in terms of the dose and the quality of the radiation. One of the best measures of the quality of neutron irradiation is the dose mean lineal energy. At very low dose rates this can be determined by measuring individual energy deposition events, and calculating the dose mean of the event size. However, at the dose rates that are normally required for biology experiments, the individual events can not be separated by radiation detectors. However, the total energy deposited in a specified time interval can be measured. This total energy has a random variation which depends on the size of the individual events, so the dose mean lineal energy can be calculated from the variance of repeated measurements of the energy deposited in a fixed time. We have developed a specialized charge integration circuit for the measurement of the charge produced in a small ion chamber in typical neutron irradiation exp...

Optimized dose distribution of a high dose rate vaginal cylinder

International Nuclear Information System (INIS)

Li Zuofeng; Liu, Chihray; Palta, Jatinder R.

1998-01-01

Purpose: To present a comparison of optimized dose distributions for a set of high-dose-rate (HDR) vaginal cylinders calculated by a commercial treatment-planning system with benchmark calculations using Monte-Carlo-calculated dosimetry data. Methods and Materials: Optimized dose distributions using both an isotropic and an anisotropic dose calculation model were obtained for a set of HDR vaginal cylinders. Mathematical optimization techniques available in the computer treatment-planning system were used to calculate dwell times and positions. These dose distributions were compared with benchmark calculations with TG43 formalism and using Monte-Carlo-calculated data. The same dwell times and positions were used for a quantitative comparison of dose calculated with three dose models. Results: The isotropic dose calculation model can result in discrepancies as high as 50%. The anisotropic dose calculation model compared better with benchmark calculations. The differences were more significant at the apex of the vaginal cylinder, which is typically used as the prescription point. Conclusion: Dose calculation models available in a computer treatment-planning system must be evaluated carefully to ensure their correct application. It should also be noted that when optimized dose distribution at a distance from the cylinder surface is calculated using an accurate dose calculation model, the vaginal mucosa dose becomes significantly higher, and therefore should be carefully monitored

The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

Science.gov (United States)

McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

2017-07-07

The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Experimental evaluation of a MOSFET dosimeter for proton dose measurements