PURPOSE: The complex relationship between linear energy transfer (LET) and cellular response to radiation is not yet fully elucidated. To better characterize DNA damage after irradiations with therapeutic protons, we monitored formation and disappearance of DNA double-strand breaks (DNA DSB) as a function of LET and time. Comparisons with conventional γ-rays and high LET carbon ions were also performed. MATERIALS AND METHODS: In the present work, we performed immunofluorescence-based assay to determine the amount of DNA DSB induced by different LET values along the 62 MeV therapeutic proton Spread out Bragg peak (SOBP) in three cancer cell lines, i.e. HTB140 melanoma, MCF-7 breast adenocarcinoma and HTB177 non-small lung cancer cells. Time dependence of foci formation was followed as well. To determine irradiation positions, corresponding to the desired LET values, numerical simulations were carried out using Geant4 toolkit. We compared γ-H2AX foci persistence after irradiations with protons to that of γ-rays and carbon ions. RESULTS: With the rise of LET values along the therapeutic proton SOBP, the increase of γ-H2AX foci number is detected in the three cell lines up to the distal end of the SOBP, while there is a decrease on its distal fall-off part. With the prolonged incubation time, the number of foci gradually drops tending to attain the residual level. For the maximum number of DNA DSB, irradiation with protons attain higher level than that of γ-rays. Carbon ions produce more DNA DSB than protons but not substantially. The number of residual foci produced by γ-rays is significantly lower than that of protons and particularly carbon ions. Carbon ions do not produce considerably higher number of foci than protons, as it could be expected due to their physical properties. CONCLUSIONS: In situ visualization of γ-H2AX foci reveal creation of more lesions in the three cell lines by clinically relevant proton SOBP than γ-rays. The lack of significant differences in the number of γ-H2AX foci between the proton and carbon ion-irradiated samples suggests an increased complexity of DNA lesions and slower repair kinetics after carbon ions compared to protons. For all three irradiation types, there is no major difference between the three cell lines shortly after irradiations, while later on, the formation of residual foci starts to express the inherent nature of tested cells, therefore increasing discrepancy between them.

• MeSH
• dvouřetězcové zlomy DNA účinky záření   MeSH
• lidé MeSH
• lineární přenos energie * MeSH
• nádorové buněčné linie MeSH
• oprava DNA účinky záření   MeSH
• protony * MeSH
• relativní biologická účinnost MeSH
• viabilita buněk účinky záření   MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The biophysical simulation tool PARTRAC has been primarily developed to model radiation physics, chemistry and biology on nanometre to micrometre scales. However, the tool can be applied in simulating radiation effects in an event-by-event manner over macroscopic volumes as well. Benchmark simulations are reported showing that PARTRAC does reproduce the macroscopic Bragg peaks of proton beams, although the penetration depths are underestimated by a few per cent for high-energy beams. PARTRAC also quantifies the increase in DNA damage and its complexity along the beam penetration depth. Enhanced biological effectiveness is predicted in particular within distal Bragg peak parts of therapeutic proton beams.

• MeSH
• algoritmy MeSH
• DNA účinky záření   MeSH
• dvouřetězcové zlomy DNA účinky záření   MeSH
• lineární přenos energie MeSH
• metoda Monte Carlo MeSH
• počítačová simulace * MeSH
• poškození DNA MeSH
• protonová terapie MeSH
• protony MeSH
• relativní biologická účinnost MeSH
• software MeSH
• voda MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH

The topic of the article is to define the average value of linear energy transfer (LET) for carcinogenic effects of radon progeny. The microdosimetric model of boundary specific energy is used. It follows that the effect at high LET should decrease approximately with the third power of LET. This is verified by the analysis of the relationship between radiation effects ratio and LET in published experiments with oncogenic transformation of mammalian cells irradiated with the monoenergetic alpha particles. If these cells are exposed with the radon irradiator, our analysis leads us to conclude that the oncogenic effect of radon progeny is comparable to that of alpha particles with a LET of 75 keV/μm. It is about a quarter lower than the LET value, where the effect of the monoenergetic alpha particles reaches its maximum level. Some implications for lung cancer due to radon inhalation may also be carefully examined.

• MeSH
• alfa částice * MeSH
• dceřiné produkty radonu škodlivé účinky   MeSH
• karcinogeneze * MeSH
• křeček rodu Mesocricetus MeSH
• lidé MeSH
• lineární přenos energie * MeSH
• myši inbrední C3H MeSH
• myši MeSH
• nádorová transformace buněk účinky záření   MeSH
• nádory plic MeSH
• nádory vyvolané zářením MeSH
• onkogeny MeSH
• radon škodlivé účinky   MeSH
• relativní biologická účinnost * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.

• MeSH
• alfa částice terapeutické užití   MeSH
• bor chemie   terapeutické užití   MeSH
• borohydridy chemie   MeSH
• buněčná smrt účinky záření   MeSH
• chromozomální aberace účinky záření   MeSH
• cyklotrony MeSH
• DNA nádorová genetika   metabolismus   účinky záření   MeSH
• fluorescenční barviva chemie   MeSH
• izotopy uhlíku chemie   MeSH
• karyotypizace MeSH
• kombinovaná terapie přístrojové vybavení   metody   MeSH
• lidé MeSH
• lineární přenos energie MeSH
• nádorové buněčné linie MeSH
• nádory prostaty patologie   radioterapie   MeSH
• neutrony * MeSH
• poškození DNA MeSH
• protonová terapie * přístrojové vybavení   metody   MeSH
• relativní biologická účinnost MeSH
• sulfhydrylové sloučeniny chemie   MeSH
• terapie metodou neutronového záchytu (bor-10) přístrojové vybavení   metody   MeSH
• vztah dávky záření a odpovědi MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In recent years, there is an increased interest in using scanning modes in proton therapy, due to the more conformal dose distributions, thanks to the spot-weighted dose delivery. The dose rate in each spot is however much higher than the dose rate when using passive irradiation modes, which could affect the cell response. The purpose of this work was to investigate how the relative biological effectiveness changes along the spread-out Bragg peak created by protons delivered by the pencil beam scanning mode. Cell survival and micronuclei formation were investigated in four positions along the spread-out Bragg peak for various doses. Monte Carlo simulations were used to estimate the dose-averaged linear energy transfer values in the irradiation positions. The cell survival was found to decrease the deeper the sample was placed in the spread-out Bragg peak, which corresponds to the higher linear energy transfer values found using Monte Carlo simulations. The micronuclei frequencies indicate more complex cell injuries at that distal position compared to the proximal part of the spread-out Bragg peak. The relative biological effectiveness determined in this study varies significantly and systematically from 1.1, which is recommended value by the International Commission on Radiation Units, in all the studied positions. In the distal position of spread-out Bragg peak the relative biological effectiveness values were found to be 2.05 ± 0.44, 1.85 ± 0.42, 1.53 ± 0.38 for survival levels 90, 50 and 10%, respectively.

• MeSH
• lidé MeSH
• lineární přenos energie MeSH
• mikrojaderné testy MeSH
• novorozenec MeSH
• počítačová simulace MeSH
• protony * MeSH
• radiometrie MeSH
• relativní biologická účinnost * MeSH
• viabilita buněk účinky záření   MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: To investigate the clinical implications of a variable relative biological effectiveness (RBE) on proton dose fractionation. Using acute exposures, the current clinical adoption of a generic, constant cell killing RBE has been shown to underestimate the effect of the sharp increase in linear energy transfer (LET) in the distal regions of the spread-out Bragg peak (SOBP). However, experimental data for the impact of dose fractionation in such scenarios are still limited. METHODS AND MATERIALS: Human fibroblasts (AG01522) at 4 key depth positions on a clinical SOBP of maximum energy 219.65 MeV were subjected to various fractionation regimens with an interfraction period of 24 hours at Proton Therapy Center in Prague, Czech Republic. Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and parameterized using a linear quadratic formalism. RESULTS: Significant variations in the cell killing RBE for fractionated exposures along the proton dose profile were observed. RBE increased sharply toward the distal position, corresponding to a reduction in cell sparing effectiveness of fractionated proton exposures at higher LET. The effect was more pronounced at smaller doses per fraction. Experimental survival fractions were adequately predicted using a linear quadratic formalism assuming full repair between fractions. Data were also used to validate a parameterized variable RBE model based on linear α parameter response with LET that showed considerable deviations from clinically predicted isoeffective fractionation regimens. CONCLUSIONS: The RBE-weighted absorbed dose calculated using the clinically adopted generic RBE of 1.1 significantly underestimates the biological effective dose from variable RBE, particularly in fractionation regimens with low doses per fraction. Coupled with an increase in effective range in fractionated exposures, our study provides an RBE dataset that can be used by the modeling community for the optimization of fractionated proton therapy.

• MeSH
• analýza kolonii tvořících jednotek MeSH
• fibroblasty účinky záření   MeSH
• frakcionace dávky záření MeSH
• lidé MeSH
• lineární přenos energie * MeSH
• metoda Monte Carlo MeSH
• nejistota MeSH
• protonová terapie metody   MeSH
• protony * MeSH
• relativní biologická účinnost * MeSH
• viabilita buněk MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

An internal contamination with (241)Am was detected in a worker during a routine monitoring of workers from a company producing Am sources for smoke detectors and Am-Be neutron sources. During the 4-year period after the exposure, the number of urine and faecal samples from the worker were analysed; in vivo measurements were also performed. Specific values for absorption parameters of the human respiratory tract model and particle transport values were applied to improve the model fit to the measurement data. A good agreement of the bioassay data with the so-modified model predictions was obtained.

• MeSH
• americium farmakokinetika   moč   MeSH
• biotest MeSH
• celotělové počítání MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• kosti a kostní tkáň účinky záření   MeSH
• lidé MeSH
• obsah radioaktivních látek v organizmu MeSH
• plíce účinky záření   MeSH
• počítačová simulace MeSH
• pracovní expozice analýza   MeSH
• relativní biologická účinnost MeSH
• tkáňová distribuce MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

Radon is recognized as a public health concern for indoor exposure. Precise quantification derived from occupational exposure in miners is still needed for estimating the risk and the factors that modify the dependence on cumulated exposure. The present paper reports on relationship between radon exposure and lung cancer risk in French and Czech cohorts of uranium miners (n = 10,100). Miners from these two cohorts are characterized by low levels of exposure (average cumulated exposure of less than 60 WLM) protracted over a long period (mean duration of exposure of 10 years) and by a good quality of individual exposure estimates (95% of annual exposures based on radon measurements). The modifying effect of the quality of exposure on the risk is analyzed. A total of 574 lung cancer deaths were observed, which is 187% higher than expected from the national statistics. This significantly elevated risk is strongly associated with cumulated radon exposure. The estimated overall excess relative risk per WLM is 0.027 (95% CI: 0.017-0.043, related to measured exposures). For age at exposure of 30 and 20 years since exposure, the ERR/WLM is 0.042, and this value decreases by approximately 50% for each 10-year increase in age at exposure and time since exposure. The present study emphasizes that the quality of exposure estimates is an important factor that may substantially influence results. Time since exposure and simultaneously age at exposure were the most important effect modifiers. No inverse exposure-rate effect below 4 WL was observed. The results are consistent with estimates of the BEIR VI report using the concentration model at an exposure rate below 0.5 WL.

• MeSH
• analýza přežití MeSH
• časové faktory MeSH
• dávka záření MeSH
• dospělí MeSH
• financování organizované MeSH
• hodnocení rizik metody   MeSH
• hornictví statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory plic mortalita   MeSH
• nádory vyvolané zářením mortalita   MeSH
• obsah radioaktivních látek v organizmu MeSH
• pracovní expozice statistika a číselné údaje   MeSH
• radon analýza   MeSH
• relativní biologická účinnost MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• uran analýza   MeSH
• věk při počátku nemoci MeSH
• věkové rozložení MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Česká republika MeSH
• Francie MeSH

PURPOSE: The purpose of our study is to examine phospho-ATF-2(Thr-69/71) (phospho-activating transcription factor-2, p-ATF-2), phospho-CREB(Ser-133) (phospho-cAMP response binding element protein, p-CREB), and phospho-c-Myc(Thr-58/Ser-62) (phosho-myelocytomatosis protooncogene, p-c-Myc) expression in irradiated rat colon transversum. MATERIALS AND METHODS: Male Wistar rats were randomly divided to 28 groups and irradiated with whole-body gamma-radiation of 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 Gy. Samples were taken 4 and 24 hours after the irradiation, immunohistochemically stained. P-ATF-2, p-CREB, and p-c-Myc expression was measured. RESULTS: We measured increased cytoplasmatic p-ATF-2 expression 4 hours after irradiation by 0.25 - 1, 10 Gy and 24 hours after irradiation by 0.5 - 1, 10 Gy. Increased cytoplasmatic p-CREB expression was found 4 hours after irradiation by 0.25 - 1, 9, 10 Gy and 24 hours after irradiation by 0.25 - 1, 4, 10 Gy. Increased p-c-Myc cytoplasmatic expression was found 4 hours after irradiation by 0.25, 0.75, 4, 5 Gy and 24 hours after irradiation by 0.75, 1, 10 Gy. Nuclear p-ATF-2, p-CREB, and p-c-Myc expressions were similar to their cytoplasmatic expressions. CONCLUSION: The detection of p-ATF-2 and p-CREB might be considered as a perspective biodosimetric tool for irradiated enterocytes in vivo. The use of p-c-Myc appears to be controversial due to the ambivalent expression values.

• MeSH
• biotest metody   MeSH
• celotělové ozáření MeSH
• celotělové počítání metody   MeSH
• exprese genu účinky záření   MeSH
• financování organizované MeSH
• kolon metabolismus   účinky záření   MeSH
• krysa rodu rattus MeSH
• obsah radioaktivních látek v organizmu MeSH
• potkani Wistar MeSH
• protein vázající element responzivní pro cyklický AMP metabolismus   MeSH
• relativní biologická účinnost MeSH
• transkripční faktor ATF2 metabolismus   MeSH
• záření gama MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

We have focused on the usage of MCNP code for calculation of Gamma Knife radiation field parameters with a homogenous polystyrene phantom. We have investigated several parameters of the Leksell Gamma Knife radiation field and compared the results with other studies based on EGS4 and PENELOPE code as well as the Leksell Gamma Knife treatment planning system Leksell GammaPlan (LGP). The current model describes all 201 radiation beams together and simulates all the sources in the same time. Within each beam, it considers the technical construction of the source, the source holder, collimator system, the spherical phantom, and surrounding material. We have calculated output factors for various sizes of scoring volumes, relative dose distributions along basic planes including linear dose profiles, integral doses in various volumes, and differential dose volume histograms. All the parameters have been calculated for each collimator size and for the isocentric configuration of the phantom. We have found the calculated output factors to be in agreement with other authors' works except the case of 4 mm collimator size, where averaging over the scoring volume and statistical uncertainties strongly influences the calculated results. In general, all the results are dependent on the choice of the scoring volume. The calculated linear dose profiles and relative dose distributions also match independent studies and the Leksell GammaPlan, but care must be taken about the fluctuations within the plateau, which can influence the normalization, and accuracy in determining the isocenter position, which is important for comparing different dose profiles. The calculated differential dose volume histograms and integral doses have been compared with data provided by the Leksell GammaPlan. The dose volume histograms are in good agreement as well as integral doses calculated in small calculation matrix volumes. However, deviations in integral doses up to 50% can be observed for large volumes such as for the total skull volume. The differences observed in treatment of scattered radiation between the MC method and the LGP may be important in this case. We have also studied the influence of differential direction sampling of primary photons and have found that, due to the anisotropic sampling, doses around the isocenter deviate from each other by up to 6%. With caution about the details of the calculation settings, it is possible to employ the MCNP Monte Carlo code for independent verification of the Leksell Gamma Knife radiation field properties.

• MeSH
• algoritmy MeSH
• analýza selhání vybavení MeSH
• biologické modely MeSH
• celková dávka radioterapie MeSH
• design vybavení MeSH
• lidé MeSH
• metoda Monte Carlo MeSH
• nádory mozku radioterapie   MeSH
• obsah radioaktivních látek v organizmu MeSH
• plánování radioterapie pomocí počítače metody   MeSH
• počítačová simulace MeSH
• radiochirurgie metody   přístrojové vybavení   MeSH
• radiometrie metody   MeSH
• relativní biologická účinnost MeSH
• statistické modely MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• hodnotící studie MeSH