title: Monte Carlo simulation of ionizing radiation induced DNA strand breaks utilizing coarse grained high-order chromatin structures.
abstract: Ionizing radiation threatens genome integrity by causing DNA damage. Monte Carlo simulation of the interaction of a radiation track structure with DNA provides a powerful tool for investigating the mechanisms of the biological effects. However, the more or less oversimplification of the indirect effect and the inadequate consideration of high-order chromatin structures in current models usually results in discrepancies between simulations and experiments, which undermine the predictive role of the models. Here we present a biophysical model taking into consideration factors that influence indirect effect to simulate radiation-induced DNA strand breaks in eukaryotic cells with high-order chromatin structures. The calculated yields of single-strand breaks and double-strand breaks (DSBs) for photons are in good agreement with the experimental measurements. The calculated yields of DSB for protons and α particles are consistent with simulations by the PARTRAC code, whereas an overestimation is seen compared with the experimental results. The simulated fragment size distributions for (60)Co γ irradiation and α particle irradiation are compared with the measurements accordingly. The excellent agreement with (60)Co irradiation validates our model in simulating photon irradiation. The general agreement found in α particle irradiation encourages model applicability in the high linear energy transfer range. Moreover, we demonstrate the importance of chromatin high-order structures in shaping the spectrum of initial damage.
authors.affiliation: State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing, 100871, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.forename: Gen
authors.initials: G
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000512:Alpha Particles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000528:radiation effects*; D004247:DNA / Q000528:radiation effects*; D053903:DNA Breaks, Double-Stranded; D006801:Humans; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D011522:Protons
chemical_list: D002843:Chromatin; D011522:Protons; D004247:DNA