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.

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Cesium-bearing microparticles (Cs-BMPs) can reach the human respiratory system after inhalation, resulting in chronic local internal exposure. We previously investigated the spatial distribution of DNA damage induced in areas around a Cs-BMP; however, the biological impacts have not been fully clarified due to the limited amount of data. Here, we investigated the inflammatory signaling and DNA damage responses after local exposure to a Cs-BMP in vitro. We used two normal human lung cell lines, i.e., lung fibroblast cells (WI-38) and bronchial epithelial cells (HBEC3-KT). After 24 h exposure to a Cs-BMP, inflammation was evaluated by immunofluorescent staining for nuclear factor κB (NF-κB) p65 and cyclooxygenase 2 (COX-2). The number of DNA double-strand breaks (DSBs) was also detected by means of phospholylated histone H2AX (γ-H2AX) focus formation assay. Cs-BMP exposure significantly increased NF-κB p65 and COX-2 expressions, which were related to the number of γ-H2AX foci in the cell nuclei. Compared to the uniform (external) exposure to 137Cs γ-rays, NF-κB tended to be more activated in the cells proximal to the Cs-BMP, while both NF-κB p65 and COX-2 were significantly activated in the distal cells. Experiments with chemical inhibitors for NF-κB p65 and COX-2 suggested the involvement of such inflammatory responses both in the reduced radiosensitivity of the cells proximal to Cs-BMP and the enhanced radiosensitivity of the cells distal from Cs-BMP. The data show that local exposure to Cs-BMP leads to biological effects modified by the NF-κB pathway, suggesting that the radiation risk for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.

Hypoxic cancer cells within solid tumours show radio-resistance, leading to malignant progression in fractionated radiotherapy. When prescribing dose to tumours under heterogeneous oxygen pressure with intensity-modulated radiation fields, intercellular signalling could have an impact on radiosensitivity between in-field and out-of-field (OF) cells. However, the impact of hypoxia on radio-sensitivity under modulated radiation intensity remains to be fully clarified. Here, we investigate the impact of hypoxia on in-field and OF radio-sensitivities using two types of cancer cells, DU145 and H1299. Using a nBIONIX hypoxic culture kit and a shielding technique to irradiate 50% of a cell culture flask, oxygen enhancement ratios for double-strand breaks (DSB) and cell death endpoints were determined. These in vitro measurements indicate that hypoxia impacts OF cells, although the hypoxic impacts on OF cells for cell survival were dose-dependent and smaller compared to those for in-field and uniformly irradiated cells. These decreased radio-sensitivities of OF cells were shown as a consistent tendency for both DSB and cell death endpoints, suggesting that radiation-induced intercellular communication is of importance in advanced radiotherapy dose-distributions such as with intensity-modulated radiotherapy.

Radiation weighting factor wR for photons and electrons has been defined as unity independently of the energy of the particles. However, the biological effects depend on the incident energies according to in vitro experimental data. In this study, we have quantified the energy concentration along electron tracks in terms of dose-mean lineal energy (yD) on chromosome (micro-meter) and DNA (nano-meter) order scales by Monte Carlo simulations, and evaluated the impact of photon energies on DNA double-strand break (DNA-DSB) induction from an experimental study of irradiated cells. Our simulation result shows that the yD values for diagnostic X-rays (60–250 kVp) are higher than that for therapeutic X-rays (linac 6 MV), which agrees well with the tissue equivalent proportional counter (TEPC) measurements. The relation between the yD values and the numbers of γ-H2AX foci for various photon energy spectra suggests that low energy X-rays induce DNA-DSB more efficiently than higher energy X-rays even at the same absorbed dose (e.g., 1.0 Gy). The relative biological effectiveness based on DNA-DSBs number (RBEDSB) is proportionally enhanced as the yD value increases, demonstrating that the biological impact of the photon irradiation depends on energy concentration along radiation tracks of electrons produced in the bio-tissues. Ultimately, our study implies that the value of wR for photons varies depending on their energies.