ABSTRACT
Boron has been suggested to enhance the biological effectiveness of proton beams in the Bragg peak region via the p + 11B â 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.
Subject(s)
Boron Neutron Capture Therapy , Proton Therapy , Humans , Boron Neutron Capture Therapy/methods , Proton Therapy/methods , Cell Line, Tumor , Male , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/drug therapy , Glioblastoma/radiotherapy , Glioblastoma/drug therapy , Boron/chemistry , Cell Survival/drug effects , Cell Survival/radiation effects , ProtonsABSTRACT
Hyperthermia along with hydrocortisone (HC) are proven teratogens that can negatively influence embryo development during early pregnancy. Proliferation of cells is one of the main developmental processes during the early embryogenesis. This study was focused on testing the effect of elevated temperature and HC addition on proliferation of cells in in vitro cultures. The V79-4 cell line was treated with HC and cultured in vitro at 37 °C or 39 °C, respectively. To reveal the effect of both factors, the proliferation of cells cultured under different conditions was evaluated using various approaches (colony formation assay, generation of growth curves, computation of doubling times, and mitotic index estimation). Our results indicate that a short-term exposure to elevated temperature slightly stimulates and a long-term exposure suppresses cell proliferation. However, HC (0.1 mg/ml) acts as a stimulator of cell proliferation. Interestingly, the interaction of HC and long-term elevated temperature (39 °C) exposure results in at least partial compensation of the negative impact of elevated temperature by HC addition and in higher proliferation if compared with cells cultured at 39 °C without addition of HC.
Subject(s)
Cell Proliferation , Fibroblasts , Hydrocortisone , Cell Proliferation/drug effects , Hydrocortisone/pharmacology , Fibroblasts/drug effects , Fibroblasts/cytology , Fibroblasts/metabolism , Animals , Cells, Cultured , Temperature , Cricetulus , Hot TemperatureABSTRACT
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.
Subject(s)
Boron Neutron Capture Therapy , Proton Therapy , Boron , Neutrons , ProtonsABSTRACT
LET spectra can be measured by track-etched detectors. However, these detectors are not able to identify the type of interacting particles. Monte Carlo simulations can provide this missing information. In this work, Monte Carlo simulations based on the EURADOS Work Group 9 experiment consisting of systematic 3D mapping of out-of-field doses and LET spectra in a prototype water phantom were performed. The simulations aimed to identify the types of particles contributing to the out-of-field LET spectra. The total absorbed dose, LET and energy spectra were calculated. The calculated dose distributions and LET spectra were compared with the ones measured by radiophotoluminiscence and track-etched detectors. The out-of-field particles and their LET values were identified. No statistically significant differences between the measured and simulated spectra were revealed in the LET range of 100-2000 keV µm-1.
Subject(s)
Proton Therapy , Protons , Linear Energy Transfer , Monte Carlo Method , Radiotherapy Dosage , WaterABSTRACT
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.