An improvement of the Local Effect Model (LEM) is presented which takes clustered DNA damage into account. Single strand breaks (SSBs) and double strand breaks (DSBs) are distributed stochastically onto the DNA molecule and additional DSBs are recorded. Consideration of this additional damage leads to a modification of the underlying photon survival curve at high doses. As a consequence of the new approach, the ratio of maximum relative biological effectiveness (RBE) values to minimum RBEs is increased. This can be understood in terms of a higher radiation effect resulting from the cluster damage at high local doses. We find that the extended LEM including cluster effects reproduces experimental data for V79 cells significantly better than the original LEM.
Double-strand breaks (DSBs) are the most critical radiation-induced lesions, because they result in the fragmentation of the DNA molecule and because a single unrepaired DSB may lead to cell death. We present the results of radiation-induced fragmentation of plasmid DNA analyzed by atomic force microscopy (AFM) to allow the visualization of individual DNA molecules. Linear PhiX174 plasmid DNA was exposed to a wide range of doses of low-LET X rays and high-LET carbon, nickel and uranium ions. The induced DNA fragments were detected and measured based on the recorded AFM images and fragment length distributions were derived for each radiation type and dose. The results show a dose- and radiation type-dependent DNA fragmentation with a significantly larger fraction of short fragments produced by high-LET radiation compared to X rays. This can be considered as experimental evidence of DSB clustering due to inhomogeneous energy deposition at the level of the plasmid DNA molecule. Additionally, the experimentally derived fragment profiles were compared and found to be in agreement with the prediction of a model simulating the fragmentation of DNA molecules induced by radiation.
Purpose: To analyze predictions of the relative biological effectiveness (RBE) for carbon ion treatment planning based on different descriptions of the radial dose distributions around ion tracks and to discuss the implications on clinically relevant depth dose profiles. Method and Materials: We investigate the impact of track structure on calculations of RBE values using the Local Effect Model (LEM). It calculates the RBE for cell lines or tissues starting from the corresponding experimental/clinical photon data and an amorphous track structure model. Different track structure models that use energy‐dependent as well as energy‐independent core radii are investigated and compared to in vitro and in vivo data. Additionally, we apply them to calculate the biologically effective dose along a spread‐out Bragg peak for typical chordoma treatments. Results: We show that the LEM is sensitive to different descriptions of the radial dose distributions. However, by changing a single model parameter of the photon reference curve, reasonable RBE values can be achieved for all dose distributions. The general improvement of predictions using a modified version of the LEM with an energy‐dependent core radius is demonstrated by comparison to in vitro data of human cell lines and to experimental data of the radiation tolerance of the rat spinal cord. Additionally, we find a larger therapeutic ratio for the modified model version relative to the original LEM for a typical treatment scenario for chordoma patients. Conclusion: The Local Effect Model is sensitive to the inner part (few nanometers) of different track structure descriptions. Since these interactions of ions with liquid water are neither well understood experimentally nor theoretically, more studies should address the energy deposition around ion tracks. This will be in particular useful for further optimization of carbon ion therapy in general and with respect to comparison with other treatment modalities like protons or IMRT.
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