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The advancement of multidisciplinary research fields dealing with ionising radiation induced biological damage-radiobiology, radiation physics, radiation protection and, in particular, medical physics-requires a clear mechanistic understanding of how cellular damage is induced by ionising radiation. Monte Carlo (MC) simulations provide a promising approach for the mechanistic simulation of radiation transport and radiation chemistry, towards the in silico simulation of early biological damage. We have recently developed a fully integrated MC simulation that calculates early single strand breaks (SSBs) and double strand breaks (DSBs) in a fractal chromatin based human cell nucleus model. The results of this simulation are almost equivalent to past MC simulations when considering direct/indirect strand break fraction, DSB yields and fragment distribution. The simulation results agree with experimental data on DSB yields within 13.6% on average and fragment distributions agree within an average of 34.8%.

An overview of the electromagnetic (EM) physics of the Geant4 toolkit is presented. Two sets of EM models are available: the "Standard" initially focused on high energy physics (HEP) while the "Low-energy" was developed for medical, space and other applications. The "Standard" models provide a faster computation but are less accurate for keV energies, the "Low-energy" models are more CPU time consuming. A common interface to EM physics models has been developed allowing a natural combination of ultra-relativistic, relativistic and low-energy models for the same run providing both precision and CPU performance. Due to this migration additional capabilities become available. The new developments include relativistic models for bremsstrahlung and e+e-pair production, models of multiple and single scattering, hadron/ion ionization, microdosimetry for very low energies and also improvements in existing Geant4 models. In parallel, validation suites and benchmarks have been intensively developed.

It appears that protons reduce the number of HTB140 cells by apoptosis as well as by severe DNA damage, while gamma-rays eliminate viable cells primarily by the production of irreparable DNA damage. Protons have an increased RBE relative to gamma-rays.

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Survival data confirmed very high radioresistance of HTB140 cells. An effect similar to low-dose hyper radiosensitivity (HRS) was observed for order of magnitude larger doses. Better response of cells to protons than to gamma-rays was illustrated by rather high RBE. Strong killing ability at the SOBP distal declining edge was the consequence of increasing proton linear energy transfer.

Effects of single irradiation with gamma rays and protons on human HTB140 melanoma cell growth were compared. Exponentially growing cells were irradiated close to the Bragg peak maximum of the unmodulated 62 MeV protons, as well as with (60)Co gamma rays. Applied doses ranged from 8 to 24 Gy. Viability of cells and proliferation capacity were assessed 7 days after irradiation. Induction of apoptosis and cell cycle phase redistribution were observed 6 and 48 h after irradiation. Significant inhibitory effects of both irradiation qualities were detected 7 days after irradiation. Important reduction of HTB140 cell viability was observed after irradiation with protons. Almost linear and highly significant (P < 0.001) decrease of cell proliferation was observed 7 days after irradiation with gamma rays and protons, as compared to nonirradiated controls. Protons induced apoptosis, both 6 and 48 h after irradiation. With the increase of post-irradiation incubation time, number of apoptotic cells decreased. Exposure of HTB140 cells to gamma rays did not provoke apoptotic cell death. Important number of cells in G1-S phase, detected by the cell cycle phase redistribution analyses, suggested high metabolic activity of irradiated melanoma cells within the first 48 h. Both irradiation qualities caused modest G2-M arrest 6 and 48 h after irradiation, thus supporting results that illustrated high radioresistance of HTB140 cells.

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