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1.
Radiat Prot Dosimetry ; 186(1): 143-147, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-30809673

RESUMO

Progress in the field of ionising radiation (IR) metrology achieved in the BioQuaRT project raised the question to what extent radiobiological investigations would benefit from metrological support of the applied methodologies. A panel of experts from the medical field, fundamental research and radiation protection attended a workshop at Physikalisch-Technische Bundesanstalt to consult on metrology needs related to biological radiation effects. The panel identified a number of metrological needs including the further development of experimental and computational techniques for micro- and nanodosimetry, together with the determination of related fundamental material properties and the establishment of rigorous uncertainty budgets. In addition to this, a call to develop a metrology support for assisting quality assurance of radiobiology experiments was expressed. Conclusions from the workshop were presented at several international conferences for further discussion with the scientific community and stakeholder groups that led to an initiative within the metrology community to establish a European Metrology Network on biological effects of IR.


Assuntos
Bioensaio/métodos , Proteção Radiológica/normas , Radiobiologia/organização & administração , Radiobiologia/normas , Radiometria/métodos , Humanos , Proteção Radiológica/métodos , Radiação Ionizante
2.
Radiat Prot Dosimetry ; 180(1-4): 278-281, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29069437

RESUMO

We present predictions of neutron relative biological effectiveness (RBE) for cell irradiations with neutron beams at PTB-Braunschweig. A neutron RBE model is adopted to evaluate initial DNA damage induction given the neutron-induced charged particle field. RBE values are predicted for cell exposures to quasi-monoenergetic beams (0.56 MeV, 1.2 MeV) and to a broad energy distribution neutron field with dose-averaged energy of 5.75 MeV. Results are compared to what obtained with our RBE predictions for neutrons at similar energies, when a 30-cm sphere is irradiated in an isotropic neutron field. RBE values for experimental conditions are higher for the lowest neutron energies, because, as expected, target geometry determines the weight of the low-effectiveness photon component of the neutron dose. These results highlight the importance of characterizing neutron fields in terms of physical interactions, to fully understand neutron-induced biological effects, contributing to risk estimation and to the improvement of radiation protection standards.


Assuntos
Biologia/métodos , Nêutrons , Física/métodos , Eficiência Biológica Relativa , Dano ao DNA , Relação Dose-Resposta à Radiação , Humanos , Íons , Fótons , Risco , Software
3.
Sci Rep ; 6: 32441, 2016 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-27578260

RESUMO

Ultra-short proton pulses originating from laser-plasma accelerators can provide instantaneous dose rates at least 10(7)-fold in excess of conventional, continuous proton beams. The impact of such extremely high proton dose rates on A549 human lung cancer cells was compared with conventionally accelerated protons and 90 keV X-rays. Between 0.2 and 2 Gy, the yield of DNA double strand breaks (foci of phosphorylated histone H2AX) was not significantly different between the two proton sources or proton irradiation and X-rays. Protein nitroxidation after 1 h judged by 3-nitrotyrosine generation was 2.5 and 5-fold higher in response to conventionally accelerated protons compared to laser-driven protons and X-rays, respectively. This difference was significant (p < 0.01) between 0.25 and 1 Gy. In conclusion, ultra-short proton pulses originating from laser-plasma accelerators have a similar DNA damaging potential as conventional proton beams, while inducing less immediate nitroxidative stress, which probably entails a distinct therapeutic potential.


Assuntos
Quebras de DNA de Cadeia Dupla/efeitos da radiação , DNA/efeitos da radiação , Histonas/efeitos da radiação , Prótons , Eficiência Biológica Relativa , Células A549 , Relação Dose-Resposta à Radiação , Histonas/metabolismo , Humanos , Lasers , Óxidos de Nitrogênio/metabolismo , Fosforilação , Tirosina/análogos & derivados , Tirosina/biossíntese
4.
Radiat Prot Dosimetry ; 166(1-4): 197-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25877532

RESUMO

The aim of the 'BioQuaRT' (Biologically weighted Quantities in RadioTherapy) project is to develop measurement techniques for characterising charged particle track structure on different length scales, and to correlate at the cellular level the track structure properties with the biological effects of radiation. This multi-scale approach will allow characterisation of the radiation qualities used in radiotherapy and the related biological effects. Charged-particle microbeam facilities were chosen as the platforms for all radiobiology experiments in the 'BioQuaRT' project, because they allow targeting single cells (or compartments of a cell) with a predefined number of ionising particles and correlating the cell-by-cell induced damage with type and energy of the radiation and with the number of ions per cell. Within this project, a novel in situ protocol was developed for the analysis of the misrepaired and/or unrepaired chromosome damage induced by charged-particle irradiations at the Physikalisch-Technische Bundesanstalt (PTB) ion microbeam facility. Among the cytogenetic biomarkers to detect and estimate radiation-induced DNA damage in radiobiology, chromosomal aberrations and micronuclei were chosen. The characteristics of the PTB irradiation system required the design of a special in situ assay: specific irradiation dishes with a base made from a biofoil 25-µm thick and only 3000-4000 cells seeded and irradiated per dish. This method was developed on Chinese hamster ovary (CHO) cells, one of the most commonly used cell lines in radiobiology in vitro experiments. The present protocol allows the simultaneous scoring of chromosome aberrations and micronuclei on the same irradiated dish. Thanks to its versatility, this method could also be extended to other radiobiological applications besides the single-ion microbeam irradiations.


Assuntos
Núcleo Celular/efeitos da radiação , Fenômenos Fisiológicos Celulares/efeitos da radiação , Aberrações Cromossômicas/efeitos da radiação , Dano ao DNA/efeitos da radiação , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Aceleradores de Partículas/instrumentação , Animais , Células CHO , Cricetinae , Cricetulus , Relação Dose-Resposta à Radiação , Hélio/efeitos adversos , Humanos , Transferência Linear de Energia/efeitos da radiação , Prótons , Doses de Radiação
5.
Br J Radiol ; 88(1045): 20140392, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25257709

RESUMO

Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented.


Assuntos
Radiobiologia/tendências , Radiometria/tendências , Humanos , Dosagem Radioterapêutica , Eficiência Biológica Relativa
6.
Radiat Prot Dosimetry ; 161(1-4): 23-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24262925

RESUMO

The increasing importance of ion beams in cancer therapy and the lack of experimental data for W-values for protons and heavy ions in air require new measurements. A new experimental set-up was developed at PTB and consistent measurements of W-values in argon, nitrogen and air for protons and alpha particles with energies from 0.7 to 3.5 MeV u(-1) at PTB, and for carbon ions between 3.6 and 7.0 MeV u(-1) at GSI were carried out. This publication concentrates on the measurements with protons and alpha particles at PTB. The experimental methods and the determination of corrections for recombination effects, beam-induced background radiation and additional effects are presented.


Assuntos
Partículas alfa , Neoplasias/radioterapia , Prótons , Radiometria/instrumentação , Radiometria/métodos , Ar , Argônio , Radiação de Fundo , Elétrons , Desenho de Equipamento , Gases , Radioterapia com Íons Pesados , Humanos , Íons , Nitrogênio , Dosagem Radioterapêutica
7.
Radiat Prot Dosimetry ; 143(2-4): 349-52, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21149293

RESUMO

In an inter-disciplinary collaboration of Physikalisch-Technische Bundesanstalt (PTB), German Collection of Microorganisms and Cell Cultures (DSMZ) and Heinrich-Heine University, live-cell imaging has been established at the charged-particle microbeam facility of PTB. Candidate genes participating in DNA strand-break repair pathways such as PARP-1, MRE11, MSH2, MDC1 and p53BP1 have been modified to generate fluorescent fusion proteins. Using multi-cistronic expression vectors, stable genomic integration was achieved in HT-1080 fibroblasts. The aim of this study is to characterise and use these highly reliable cell lines for studying initial steps of DNA damage responses and kinetics of repair after microbeam irradiation with high- and low-linear energy transfer (LET) particles in living cells at physiological conditions.


Assuntos
Dano ao DNA/fisiologia , Reparo do DNA/fisiologia , Fibroblastos/citologia , Fibroblastos/fisiologia , Microscopia de Fluorescência/instrumentação , Linhagem Celular , Reparo do DNA/efeitos da radiação , Desenho de Equipamento , Fibroblastos/efeitos da radiação , Humanos , Doses de Radiação
8.
Radiat Environ Biophys ; 49(3): 331-6, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20340029

RESUMO

The ambient dose equivalent from the secondary radiation produced during irradiation of a cylindrical water phantom with 200 MeV/u (12)C-ions was investigated at the biophysics cave at GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. Pencil-like ion beams were delivered by the heavy-ion synchrotron SIS18 using the slow extraction mode. Since the secondary radiation field outside the phantom is complex in its particle composition and particle energy distribution, microdosimetric methods developed for the dosimetry of the cosmic radiation field at flight altitudes, which is similar in terms of complexity, were applied. Lineal energy distributions and the ambient dose equivalent were measured with a tissue-equivalent proportional counter at different particle emission angles. An additional veto counter allowed the identification of the different contributions of charged and neutral particles. A significant increase in the mean quality factor was observed at large emission angles which could be attributed to the decreasing contributions of charged particles compared to the (relative) contributions from neutrons.


Assuntos
Carbono/uso terapêutico , Radiometria/instrumentação , Alemanha , Nêutrons , Imagens de Fantasmas , Dosagem Radioterapêutica
9.
Radiat Prot Dosimetry ; 138(1): 29-39, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19828717

RESUMO

The neoplastic transformation of human hybrid CGL1 cells is affected by perturbations from external influences such as serum batch and concentration, the number of medium changes during the 21-day expression period and cell seeding density. Nevertheless, for doses up to 1.5 Gy, published transformation frequencies for low linear energy transfer (LET) radiations (gamma-rays, MeV electrons or photons) are in good agreement, whereas for higher doses larger variations are reported. The (60)Co gamma-ray data here for doses up to 1.5 Gy, using a low-yield serum batch and only one medium change, are in agreement with published frequencies of neoplastic transformation of human hybrid cells. For 3.4 MeV alpha-particles (LET = 124 keV/mum) and 0.565 MeV monoenergetic neutrons relative to low doses of (60)Co gamma-rays, a maximum relative biological effectiveness (RBE(M)) of 2.8 +/- 0.2 and 1.5 +/- 0.2, respectively, was calculated. Surprisingly, at higher doses of (60)Co gamma-rays lower frequencies of neoplastic transformation were observed. This non-monotonic dose relationship for neoplastic transformation by (60)Co gamma-rays is likely due to the lack of a G2/M arrest observed at low doses resulting in higher transformation frequencies per dose, whereas the lower frequencies per dose observed for higher doses are likely related to the induction of a G2/M arrest.


Assuntos
Técnicas de Cultura de Células/métodos , Transformação Celular Neoplásica/patologia , Transformação Celular Neoplásica/efeitos da radiação , Radioisótopos de Cobalto , Células Híbridas/patologia , Células Híbridas/efeitos da radiação , Relação Dose-Resposta à Radiação , Raios gama , Células HeLa , Humanos , Nêutrons , Doses de Radiação , Eficiência Biológica Relativa
10.
Radiat Prot Dosimetry ; 126(1-4): 600-3, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17504749

RESUMO

A compact and transportable water calorimeter has been developed and extensively tested in the intensive, collimated neutron field of the PTB. It has been applied for absorbed dose to water measurements in the neutron therapy field of the University of Essen, in the proton therapy fields of the HMI in Berlin and at the iThemba therapy centre near Cape Town, South Africa, as well as in the (12)C-beam of the therapy facility at GSI in Darmstadt, Germany. Absolute dosimetry with relative standard uncertainties of less than 1.8% was achieved in all radiation fields. The results obtained using the water calorimeter are compared with the ionisation chamber measurements in the same radiation fields. The heat defect for the water in the calorimeter core was determined separately in independent measurements by irradiation with different charged particle beams covering a wide range of linear energy transfer.


Assuntos
Calorimetria/instrumentação , Íons Pesados , Nêutrons , Prótons , Monitoramento de Radiação/instrumentação , Proteção Radiológica/instrumentação , Água/química , Desenho de Equipamento , Análise de Falha de Equipamento , Exposição Ocupacional/análise , Doses de Radiação , Monitoramento de Radiação/métodos , Proteção Radiológica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Radiat Environ Biophys ; 44(3): 211-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16273382

RESUMO

The purpose of this study was to systematically investigate how high doses of sparsely and densely ionizing radiations influence the proliferation time of lymphocytes in short-term cultures and, consequently, the observed frequencies of dicentric and centric ring chromosomes. Peripheral blood samples from five volunteers were irradiated with high doses of 200 kV X-rays and with neutrons with a mean energy of or=2.1 MeV. First division metaphase cells were collected after different culture times of 48, 56, and 72 h and dicentrics, centric ring chromosomes, and acentric fragments were determined. The data hint at considerable mitotic delay. The main increase in the number of chromosome aberrations occurred between 48 and 72 h after an X-ray exposure and between 56 and 72 h after neutron exposure. When the data were used for a calibration of aberration frequency versus dose, subsequent dose estimations resulted, however, in comparable values. Thus, in spite of the influence of mitotic delay on observable chromosome aberrations, at least for the radiation types investigated here, a culture time of 48 h is acceptable for biological dosimetry.


Assuntos
Aberrações Cromossômicas , Cromossomos/genética , Cromossomos/efeitos da radiação , Linfócitos/efeitos da radiação , Mitose/genética , Mitose/efeitos da radiação , Radiometria/métodos , Adulto , Bioensaio/métodos , Proliferação de Células/efeitos da radiação , Células Cultivadas , Relação Dose-Resposta à Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Nêutrons/efeitos adversos , Doses de Radiação , Eficiência Biológica Relativa , Fatores de Tempo , Raios X/efeitos adversos
12.
Phys Rev Lett ; 94(14): 142501, 2005 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-15904059

RESUMO

We have set limits on contributions of scalar interactions to nuclear beta decay. A magneto-optical trap provides a localized source of atoms suspended in space, so the low-energy recoiling nuclei can freely escape and be detected in coincidence with the beta. This allows reconstruction of the neutrino momentum, and the measurement of the beta-nu correlation, in a more direct fashion than previously possible. The beta-nu correlation parameter of the 0(+)-->0(+) pure Fermi decay of (38)K(m) is a =0.9981+/-0.0030+0.0032 / -0.0037, consistent with the standard model prediction a =1.

13.
Phys Rev Lett ; 90(1): 012501, 2003 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-12570603

RESUMO

A new technique, full neutrino momentum reconstruction, is used to set limits on the admixture of heavy neutrinos into the electron neutrino. We measure coincidences between nuclear recoils and positrons from the beta decay of trapped radioactive atoms and deduce the neutrino momentum. A search for peaks in the reconstructed recoil time-of-flight spectrum as a function of positron energy is performed. The admixture upper limits range from 4 x 10(-3) to 2 x 10(-2) and are the best direct limits for neutrinos (as opposed to antineutrinos) for the mass region of 0.7 to 3.5 MeV.

14.
Phys Rev Lett ; 88(7): 072501, 2002 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-11863889

RESUMO

Angular distributions of 12C(alpha,alpha)12C have been measured for E(alpha) = 2.6-8.2 MeV, at angles from 24 to 166, yielding 12 864 data points. R-matrix analysis of the ratios of elastic scattering yields a reduced width amplitude of gamma12 = 0.47 +/- 0.06 MeV(1/2) for the Ex = 6.917 MeV (2+) state in 16O(a = 5.5 fm). The dependence of the chi2 surface on the interaction radius a has been investigated and a deep minimum is found at a = 5.42(+0.16)(-0.27) fm. Using this value of gamma12, radiative alpha capture and 16N beta-delayed alpha-decay data, the S factor is calculated at E(c.m.) = 300 keV to be S(E2)(300) = 53(+13)(-18) keV b for destructive interference between the subthreshold resonance tail and the ground state E2 direct capture.

15.
Nucleic Acids Res ; 26(21): 5004-6, 1998 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-9776766

RESUMO

An empirical formula for thermal stability (T m) prediction of PNA/DNA duplexes has been derived. The model is based on the T m as calculated for the corresponding DNA/DNA duplex employing a nearest neighbour approach, by including terms for the pyrimidine content and length of the PNA to take into account the increased thermostability of PNA/DNA hybrids and the asymmetry of the PNA-DNA heteroduplex. The predictive power of the T m prediction formula was challenged with an independent data set not used for model building. The T m of >90% of the sequences was predicted within 5 K; 98% of the predicted T ms differ by not more than 10 K from the experimentally determined T m.


Assuntos
DNA/química , Ácidos Nucleicos Peptídicos/química , Estabilidade de Medicamentos , Técnicas In Vitro , Modelos Químicos , Conformação de Ácido Nucleico , Ácidos Nucleicos Heteroduplexes/química , Termodinâmica
16.
Biophys Chem ; 69(1): 85-96, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9440211

RESUMO

A high-angle neutron fibre diffraction study of the hydration of A-DNA has been performed using the single-crystal diffractometer D19 at the Institut Laue-Langevin (Grenoble, France). The sample was prepared using deuterated DNA extracted from E. Coli cells cultured on deuterated nutrients. In common with our previous neutron fibre diffraction studies of DNA, this work exploits the ability to isotopically replace H2O around the DNA by D2O. However this study benefitted additionally from the fact that the hydrogen atoms which are covalently bonded to carbon atoms in the DNA sugars and bases were replaced by deuterium so that incoherent scattering and absorption effects were minimised. Successive cycles of Fourier synthesis and Fourier difference synthesis allowed water peaks to be identified and their positional and occupancy parameters to be refined against the observed diffraction data. The results confirm the main hydration features noted in our earlier studies with a clear network of water running along the inside edge of the major groove linking successive OI phosphate oxygen atoms. The central core of water running along the axis of the double helix is very much clearer in this work. Additionally this study shows chains of ordered water lying in the centre of the major groove.


Assuntos
DNA Bacteriano/química , Deutério , Conformação de Ácido Nucleico , Cristalografia/métodos , Escherichia coli/genética , Estrutura Molecular , Nêutrons , Água/química
17.
Basic Life Sci ; 64: 359-67, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9031520

RESUMO

The diffractometer SXD at the Rutherford Appleton Laboratory ISIS pulsed neutron source has been used to record high resolution time-of-flight Laue fiber diffraction data from DNA. These experiments, which are the first of their kind, were undertaken using fibers of DNA in the A conformation and prepared using deuterated DNA in order to minimise incoherent background scattering. These studies complement previous experiments on instrument D19 at the Institut Laue Langevin using monochromatic neutrons. Sample preparation involved drawing large numbers of these deuterated DNA fibers and mounting them in a parallel array. The strategy of data collection is discussed in terms of camera design, sample environment and data collection. The methods used to correct the recorded time-of-flight data and map it into the final reciprocal space fiber diffraction dataset are also discussed. Difference Fourier maps showing the distribution of water around A-DNA calculated on the basis of these data are compared with results obtained using data recorded from hydrogenated A-DNA on D19. Since the methods used for sample preparation, data collection and data processing are fundamentally different for the monochromatic and Laue techniques, the results of these experiments also afford a valuable opportunity to independently test the data reduction and analysis techniques used in the two methods.


Assuntos
DNA Bacteriano/química , DNA/química , Conformação de Ácido Nucleico , Cristalografia/instrumentação , Cristalografia/métodos , Cristalografia por Raios X/métodos , DNA Bacteriano/isolamento & purificação , Deutério , Escherichia coli , Modelos Moleculares , Nêutrons , Espalhamento de Radiação
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