Abstract
In this work we present results obtained in the frame of the BioQuaRT project. The objective of the study was the correlation between the number of radiation-induced double strand breaks (DSB) of the DNA molecule and the probability of detecting nuclear foci after targeted microbeam irradiation of cells with protons and alpha particles of different LET. The former were obtained by simulation with new methods integrated into Geant4-DNA that permit calculating the number of DSB in a DNA target model induced by direct and indirect radiation effects. A particular focus was laid in this work on evaluating the influence of different criteria applied to the simulated results for predicting the formation of a direct SSB. Indeed, these criteria have an important impact on the predicted number of DSB per particle track and its dependence with LET. Among the criteria tested in this work, the case that a direct radiation interaction leads to a strand break if the cumulative energy deposited in the backbone part of one nucleotide exceeds a threshold of 17.5 eV leads to the best agreement with the relative LET dependence of number of radiation induced foci. Further calculations and experimental data are nevertheless needed in order to fix the simulation parameters and to help interpreting the biological experimental data observed by immunofluorescence in terms of the DSB complexity.
Highlights
In cancer treatment using ionising radiation, dosage is quantified by the absorbed dose to water expressed in the derived SI unit gray (Gy)
As it can be seen from these values, the criteria used for determining the formation of a direct single strand breaks (SSB) in the DNA backbone has a strong influence on both the absolute value of the number of double strand breaks (DSB) per track and the dependence of DSB formation on LET
For the linear probability or the energy threshold, the indirect damages are more frequent than the direct ones and the ratio SSBindirect over SSBdirect decreases with increasing LET: in order to calculate the probability of radiation-induced foci (RIF) formation in the cell nucleus per track, the important simulated result is the cumulative probability of obtaining at least 1 DSB in the track
Summary
In cancer treatment using ionising radiation (radiotherapy), dosage is quantified by the absorbed dose to water expressed in the derived SI unit gray (Gy) Several radiotherapy modalities such as proton and ion beams require an additional weighting factor to account for increased tumor cell mortality for a given absorbed dose (as compared to a high-energy photon beam). The joint research project “Biologically weighted quantities in radiotherapy” (BioQuaRT [1], 2012-2015) aimed at laying the foundation for these biologicallyweighted radiation quantities based on a multi-scale approach This approach used measurement and simulation techniques to determine the physical properties of ionising particle tracks on different length scales (from about 2 nm to 10 μm), which were correlated with biological effects of radiation
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