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Complex DNA double-strand break (DSB), which is defined as a DSB coupled with additional strand breaks within 10 bp in this study, induced after ionizing radiation or X-rays, is recognized as fatal damage which can induce cell death with a certain probability. In general, a DSB site inside the nucleus of live cells can be experimentally detected using the γ-H2AX focus formation assay. DSB complexity is believed to be detected by analyzing the focus size using such an assay. However, the relationship between focus size and DSB complexity remains uncertain. In this study, using Monte Carlo (MC) track-structure simulation codes, i.e., an in-house WLTrack code and a Particle and Heavy Ion Transport code System (PHITS), we developed an analytical method for qualifying the DSB complexity induced by photon irradiation from the microscopic image of γ-H2AX foci. First, assuming that events (i.e., ionization and excitation) potentially induce DNA strand breaks, we scored the number of events in a water cube (5.03 × 5.03 × 5.03 nm3) along electron tracks. Second, we obtained the relationship between the number of events and the foci size experimentally measured by the γ-H2AX focus formation assay. Third, using this relationship, we evaluated the degree of DSB complexity induced after photon irradiation for various X-ray spectra using the foci size, and the experimental DSB complexity was compared to the results estimated by the well-verified DNA damage estimation model in the PHITS code. The number of events in a water cube was found to be proportional to foci size, suggesting that the number of events intrinsically related to DSB complexity at the DNA scale. The developed method was applicable to focus data measured for various X-ray spectral situations (i.e., diagnostic kV X-rays and therapeutic MV X-rays). This method would contribute to a precise understanding of the early biological impacts of photon irradiation by means of the γ-H2AX focus formation assay. [ABSTRACT FROM AUTHOR]

DNA strand breaks are induced in cells mainly composed of liquid water along ionizing radiation tracks. For estimating DNA strand break yields, track structures for electrons in liquid water in Monte Carlo simulations are of great importance; however, detailed simulations to obtain both energy deposition and free radical reaction to DNA are time-consuming processes. Here, we present a simple model for estimating yields of single- and double-strand breaks (SSB, DSB, and DSB/SSB ratio) based only on spatial patterns of inelastic interactions (i.e., ionization and electronic excitation) generated by electrons, which are evaluated by the track structure mode of Particle and Heavy Ion Transport code System without analyzing the production and diffusion of free radicals. In the present model, the number of events per track and that of a pair composed of two events within 3.4 nm (10 base pairs) were stochastically sampled for calculating SSB and DSB yields. The results calculated by this model agree well with other simulations and experimental data on the DSB yield and the DSB/SSB ratio for monoenergetic electron irradiation. This model also demonstrates the relative biological effectiveness at the DSB endpoint for various photon irradiations, indicating that the spatial pattern composed of ionization and electronic excitation without physicochemical and chemical stages is sufficient to obtain the impact of electrons on the initial DNA strand break induction. [ABSTRACT FROM AUTHOR]