BORON-ENHANCED BIOLOGICAL EFFECTIVENESS OF PROTON IRRADIATION: STRATEGY TO ASSESS THE UNDERPINNING MECHANISM.

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.

EXPERIMENTAL IN VITRO DOSIMETRY OF 223RA AND 177LU.

Targeted alpha therapy with radionuclides undergoing multiple alpha-particle decays is a promising method of nuclear medicine. To study the effectiveness of alpha versus beta emitters, survival of DU145 prostate cancer cells exposed to 223Ra or 177Lu was assessed. Per decay, the cells were much more sensitive to the alpha than beta emitter. However, per unit dose the sensitivities would be comparable, contrary to the well-known evidence, if the decay energy were deposited within the sample completely and homogeneously. Measurements by Timepix detectors showed about three times higher counts of alpha particles above than below the sample. After the first alpha decay of 223Ra to 219Rn, this gas likely moves upwards and its subsequent three alpha decays occur in the upper part of the sample. Correct estimation of absorbed dose is a critical issue when analysing in vitro data and when translating their results to clinical applications.

RADIATION DAMAGE TO DNA PLASMIDS IN THE PRESENCE OF BOROCAPTATES.

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.

Assessment of DNA damage with an adapted independent reaction time approach implemented in Geant4-DNA for the simulation of diffusion-controlled reactions between radio-induced reactive species and a chromatin fiber.

PURPOSE: Simulation of indirect damage originating from the attack of free radical species produced by ionizing radiation on biological molecules based on the independent pair approximation is investigated in this work. In addition, a new approach, relying on the independent pair approximation that is at the origin of the independent reaction time (IRT) method, is proposed in the chemical stage of Geant4-DNA. METHODS: This new approach has been designed to respect the current Geant4-DNA chemistry framework while proposing a variant IRT method. Based on the synchronous algorithm, this implementation allows us to access the information concerning the position of radicals and may make it more convenient for biological damage simulations. Estimates of the evolution of free species as well as biological hits in a segment of DNA chromatin fiber in Geant4-DNA were compared for the dynamic time step approach of the step-by-step (SBS) method, currently used in Geant4-DNA, and this newly implemented IRT. RESULTS: Results show a gain in computation time of a factor of 30 for high LET particle tracks with a better than 10% agreement on the number of DNA hits between the value obtained with the IRT method as implemented in this work and the SBS method currently available in Geant4-DNA. CONCLUSION: Offering in Geant4-DNA more efficient methods for the chemical step based on the IRT method is a task in progress. For the calculation of biological damage, information on the position of chemical species is a crucial point. This can be achieved using the method presented in this paper.

RADIATION-INDUCED PLASMID DNA DAMAGE: EFFECT OF CONCENTRATION AND LENGTH.

Plasmid DNA is commonly used as a simpler substitute for a cell in studies of early effects of ionizing radiation because it allows to determine yields of primary DNA lesions. Experimental studies often employ plasmids of different lengths, in different concentrations in the aqueous solution. Influence of these parameters on the heavy-ion induced yields of primary DNA damage has been studied, using plasmids pUC19 (2686 bp), pBR322 (4361 bp) and pKLAC2 (9107 bp) in 10 and 50 ng/µl concentration. Results demonstrate the impact of plasmid length, while no significant difference was observed between the two concentrations. The uncertainty of the results is discussed.

CR10-A PUBLIC DATABASE OF COSMIC RADIATION MEASUREMENTS AT AVIATION ALTITUDES OF ABOUT 10 KM.

Long-term measurements using silicon radiation spectrometer Liulin on board commercial aircraft have been performed since 2001; results were put into a new database, which covers more than 4500 flights with more than 130 000 measurements. Methodology and tools were developed to normalize the data with respect to latitude and altitude and thus enable comparison with other radiation detectors and with model calculations. This capability is demonstrated using data from the neutron monitor at Lomnický stít. Instead of providing data files for individual measurement period, two software solutions are delivered. First is a web-based user interface for visualizing and downloading arbitrary time window of interest from the database hosted at http://cr10.odz.ujf.cas.cz. The second is a set of interactive Python notebooks available at GitHub. Those implement the calibration, normalization and visualization methods-so the outputs can be tailored to user needs. The software and data are provided under GNU/CC license.

HOW DETECTION OF PLASMID DNA FRAGMENTATION AFFECTS RADIATION STRAND BREAK YIELDS.

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.

Comparison of cosmic rays radiation detectors on-board commercial jet aircraft.

Aircrew members and passengers are exposed to increased rates of cosmic radiation on-board commercial jet aircraft. The annual effective doses of crew members often exceed limits for public, thus it is recommended to monitor them. In general, the doses are estimated via various computer codes and in some countries also verified by measurements. This paper describes a comparison of three cosmic rays detectors, namely of the (a) HAWK Tissue Equivalent Proportional Counter; (b) Liulin semiconductor energy deposit spectrometer and (c) TIMEPIX silicon semiconductor pixel detector, exposed to radiation fields on-board commercial Czech Airlines company jet aircraft. Measurements were performed during passenger flights from Prague to Madrid, Oslo, Tbilisi, Yekaterinburg and Almaty, and back in July and August 2011. For all flights, energy deposit spectra and absorbed doses are presented. Measured absorbed dose and dose equivalent are compared with the EPCARD code calculations. Finally, the advantages and disadvantages of all detectors are discussed.

Significance of 8-oxoG in the spectrum of DNA damages caused by ionising radiation of different quality.

The yields and composition of DNA damages caused by ionising radiation depends on radiation quality. With increasing light energy transfer (LET), the proportion of isolated DNA damages with respect to cluster damaged sites decreases. Non-double strand break complex damages are induced by gamma radiation in mammalian cells at least four times more frequently that prompt DSB. The most important product of oxidative damage to DNA bases is 8-oxo-7,8-dihydroguanine (8-oxoG). The modelling of DNA damage induced by ionising radiation of different qualities was performed to assess frequencies and composition of complex damages containing 8-oxoG. The occurrence of clusters containing 8-oxoG increases from 6 to 11% for LET in the range 0.4-160 keV microm(-1). Distributions of single strand break (SSB) on opposite DNA strand around induced 8-oxoG have similar shape for different ionising radiations, but differ in their occurrence in the whole spectrum of DNA damages. The most probable configuration is a strand break localised at position +/-3 bases from 8-oxoG.