Boron has been suggested to enhance the biological effectiveness of proton beams in the Bragg peak region via the p + 11B → 3α nuclear capture reaction. However, a number of groups have observed no such enhancement in vitro or questioned its proposed mechanism recently. To help elucidate this phenomenon, we irradiated DU145 prostate cancer or U-87 MG glioblastoma cells by clinical 190 MeV proton beams in plateau or Bragg peak regions with or without 10B or 11B isotopes added as sodium mercaptododecaborate (BSH). The results demonstrate that 11B but not 10B or other components of the BSH molecule enhance cell killing by proton beams. The enhancement occurs selectively in the Bragg peak region, is present for boron concentrations as low as 40 ppm, and is not due to secondary neutrons. The enhancement is likely initiated by proton-boron capture reactions producing three alpha particles, which are rare events occurring in a few cells only, and their effects are amplified by intercellular communication to a population-level response. The observed up to 2-3-fold reductions in survival levels upon the presence of boron for the studied prostate cancer or glioblastoma cells suggest promising clinical applications for these tumour types.
- MeSH
- bor chemie MeSH
- glioblastom radioterapie farmakoterapie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prostaty radioterapie farmakoterapie MeSH
- protonová terapie * metody MeSH
- protony MeSH
- terapie metodou neutronového záchytu (bor-10) * metody MeSH
- viabilita buněk účinky léků účinky záření MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Boron derivatives have great potential in cancer diagnostics and treatment. Borocaptates are used in boron neutron capture therapy and potentially in proton boron fusion therapy. This work examines modulation effects of two borocaptate compounds on radiation-induced DNA damage. Aqueous solutions of pBR322 plasmid containing increasing concentrations of borocaptates were irradiated with 60Co gamma rays or 30 MeV protons. Induction of single and double DNA strand breaks was investigated using agarose gel electrophoresis. In this model system, representing DNA without the intervention of cellular repair mechanisms, the boron derivatives acted as antioxidants. Clinically relevant boron concentrations of 40 ppm reduced the DNA single strand breakage seven-fold. Possible mechanisms of the observed effect are discussed.
Organic inclusions in lime binders provide useful samples for radiocarbon dating of historical objects. Two Czech castles Týřov and Pyšolec from Late Middle Ages were explored, and tens of charcoals were found in their walls. The radiocarbon content of the charcoals was measured with accelerator mass spectrometry. The dating results showed that none of the charcoals were younger than the known historical ages (Týřov: 1260 - 1270, Pyšolec: 1300 - 1340), but some were considerably older. Two charcoals from Pyšolec castle dated to Palaeolithic, likely originating from fluvial sediments added as an aggregate to the mortar. When excluding these two charcoals, the others indicated most likely dates being 50-100 y older than the building dates of the castles. This systemic effect corresponds to the age of wood used for lime burning and shall be accounted for when dating mortars using charcoals.
- MeSH
- dřevěné a živočišné uhlí * MeSH
- dřevo MeSH
- radioaktivní datování * metody MeSH
- Publikační typ
- časopisecké články MeSH
Proton radiotherapy for the treatment of cancer offers an excellent dose distribution. Cellular experiments have shown that in terms of biological effects, the sharp dose distribution is further amplified, by as much as 75%, in the presence of boron. It is a matter of debate whether the underlying physical processes involve the nuclear reaction of 11B with protons or 10B with secondary neutrons, both producing densely ionizing short-ranged particles. Likewise, potential roles of intercellular communication or boron acting as a radiosensitizer are not clear. We present an ongoing research project based on a multiscale approach to elucidate the mechanism by which boron enhances the effectiveness of proton irradiation in the Bragg peak. It combines experimental with simulation tools to study the physics of proton-boron interactions, and to analyze intra- and inter-cellular boron biology upon proton irradiation.
Nowadays, the irradiation methodology in proton therapy is switching from the use of passively scattered beams to active pencil beams due to the possibility of more conformal dose distributions. The dose rates of active pencil beams are much higher than those of passive beams. The purpose of this study was to investigate whether there is any difference in the biological effectiveness of these passive and active irradiation modes. The beam qualities of double scattering and pencil beam scanning were measured dosimetrically and simulated using the Monte Carlo code. Using the medulloblastoma cell line DAOY, we performed an in vitro comparison of the two modes in two positions along the dose-deposition curve plateau and inside the Bragg peak. We followed the clonogenic cell survival, apoptosis, micronuclei, and γH2AX assays as biological endpoints. The Monte Carlo simulations did not reveal any difference between the beam qualities of the two modes. Furthermore, we did not observe any statistically significant difference between the two modes in the in vitro comparison of any of the examined biological endpoints. Our results do not show any biologically relevant differences related to the different dose rates of passive and active proton beams.
- MeSH
- apoptóza účinky záření MeSH
- histony metabolismus MeSH
- lidé MeSH
- lineární přenos energie MeSH
- metoda Monte Carlo MeSH
- mikrojaderné testy MeSH
- nádorové buněčné linie MeSH
- neutrony MeSH
- počítačová simulace MeSH
- protonová terapie * MeSH
- viabilita buněk účinky záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Track-etched detectors are commonly used also for radiation monitoring onboard International Space Station. To be registered in track-etched detectors, the particle needs to meet several criteria-it must have linear energy transfer above the detection threshold and strike the detector's surface under an angle higher than the so-called critical angle. Linear energy transfer is then estimated from calibration curve from the etch rate ratio V that is calculated from parameters of individual tracks appearing on the detector's surface after chemical etching. It has been observed that V can depend on the incident angle and this dependence can vary for different detector materials, etching and evaluating conditions. To investigate angular dependence, detectors (Harzlas TD-1) were irradiated at HIMAC by several ions under angles from 0° to 90°. The correction accounting not only for critical angle but also for dependence of V on the incident angle is introduced and applied to spectra measured onboard International Space Station.
- MeSH
- dávka záření MeSH
- ionty MeSH
- kalibrace MeSH
- kosmická loď * MeSH
- kosmické záření MeSH
- kosmický let přístrojové vybavení MeSH
- lineární přenos energie MeSH
- monitorování radiace přístrojové vybavení metody MeSH
- termoluminiscenční dozimetrie přístrojové vybavení metody MeSH
- těžké ionty * MeSH
- Publikační typ
- časopisecké články MeSH
A compromised detection of radiation-induced plasmid DNA fragments results in underestimation of calculated damage yields. Electrophoretic methods are easy and cheap, but they can only detect a part of the fragments, neglecting the shortest ones. These can be detected with atomic force microscopy, but at the expense of time and price. Both methods were used to investigate their capabilities to detect the DNA fragments induced by high-energetic heavy ions. The results were taken into account in calculations of radiation-induced yields of single and double strand breaks. It was estimated that the double strand break yield is twice as high when the fragments are at least partially detected with the agarose electrophoresis, compared to when they were completely omitted. Further increase by 13% was observed when the measured fragments were corrected for the fraction of the shortest fragments up to 300 base pairs, as detected with the atomic force microscopy. The effect of fragment detection on the single strand break yield was diminished.
Compromised detection of short DNA fragments can result in underestimation of radiation-induced clustered DNA damage. The fragments can be detected with atomic force microscopy (AFM), followed by image analysis to compute the length of plasmid molecules. Plasmid molecules imaged with AFM are represented by open or closed curves, possibly with crossings. For the analysis of such objects, a dedicated algorithm was developed, and its usability was demonstrated on the AFM images of plasmid pBR322 irradiated with 60Co gamma rays. The analysis of the set of the acquired AFM images revealed the presence of DNA fragments with lengths shorter than 300 base pairs that would have been neglected by a conventional detection method.
Experimental radiobiological studies in which the effects of ionizing radiation on a biological model are examined often highlight the biological aspects while missing detailed descriptions of the geometry, sample and dosimetric methods used. Such omissions can hinder the reproducibility and comparability of the experimental data. An application based on the Geant4 simulation toolkit was developed to design experiments using a biological solution placed in a microtube. The application was used to demonstrate the influence of the type of microtube, sample volume and energy of a proton source on the dose distribution across the sample, and on the mean dose in the whole sample. The results shown here are for samples represented by liquid water in the 0.4-, 1.5- and 2.0-ml microtubes irradiated with 20, 30 and 100 MeV proton beams. The results of this work demonstrate that the mean dose and homogeneity of the dose distribution within the sample strongly depend on all three parameters. Furthermore, this work shows how the dose uncertainty propagates into the scored primary DNA damages in plasmid DNA studies using agarose gel electrophoresis. This application is provided freely to assist users in verifying their experimental setup prior to the experiment.
