Ianik Plante

High-LET Ion Radiolysis of Water: Visualization of the Formation and Evolution of Ion Tracks and Relevance to the Radiation-Induced Bystander Effect

Abstract Muroya, Y., Plante, I., Azzam, E. I., Meesungnoen, J., Katsumura, Y. and Jay-Gerin, J-P. High-LET Ion Radiolysis of Water: Visualization of the Formation and Evolution of Ion Tracks and Relevance to the Radiation-Induced Bystander Effect. Radiat. Res. 165, 485–491 (2006). Ionizing radiation-induced bystander effects, commonly observed in cell populations exposed to high-linear energy transfer (LET) radiations, are initiated by damage to a cellular molecule which then gives rise to a toxic signal exported to neighboring cells not directly hit by radiation. A major goal in studies of this phenomenon is the identification of this initial radiation-induced lesion. Liquid water being the main constituent of biological matter, reactive species produced by water radiolysis in the cellular environment are likely to be major contributors to the induction of this lesion. In this context, the radiation track structure is of crucial importance in specifying the precise location and identity of all the radiolytic species and their subsequent signaling or damaging effects. We report here Monte Carlo track structure simulations of the radiolysis of liquid water by four different impacting ions 1H+, 4He2+, 12C6+ and 20Ne10+, with the same LET (∼70 keV/ μm). The initial radial distribution profiles of the various water decomposition products (eaq−, ·OH, H·, H2 and H2O2) for the different ions considered are presented and discussed briefly in the context of track structure theory. As an example, the formation and temporal evolution of simulated 24 MeV 4He2+ ion tracks (LET ∼26 keV/μm) are reported for each radiolytic species from 1 ps to 10 μs. The calculations reveal that the ion track structure is completely lost by ∼1 μs.

Superexchange coupling and electron transfers in large three-dimensional disordered media

Abstract The superexchange coupling ( V s ) in large three-dimensional electron-transfer systems is an intricate function of a huge number of variables suggesting the possibility for a self-averaged and universal behavior. By studying a wide class of disordered model systems presenting through-space interactions, we find that self-averaging does occur in narrow-band systems. V s is then characterized by a unique control parameter ( E / Γ ), the ratio of the energy gap to the half-bandwidth of the medium. The sign of E / Γ , distinguishing electron- from hole-transfer processes, is a major determining factor of the behavior of V s .

Monte-Carlo ''step-by-step'' simulation of the early stages of liquid water radiolysis: 3D visualization of the initial radiation track structure and its subsequent chemical development

The understanding of radiation action on liquid water, an important constituent of cells and living organisms (~85%), is a crucial prerequisite for the accurate description of the effects of radiation on more complex chemical and biological systems. Gel dosimeters, which are used to modelize the biological medium upon irradiation, also have an important water content (~90%) and are another example that requires a detailed knowledge of the complex succession of events that follow absorption in water of ionizing radiation. In the calculations reported here, the complete sequence of all individual stochastic events that take place following the irradiation of water is modeled using our Monte-Carlo code IONLYS-SBS.

Bystander effect and genomic instability in human cells and their progeny after irradiation with X rays, protons or carbon ions: role of gap junction communication

Purpose: Ionizing Radiation (IR)-induced bystander effects and genomic instability have important implication in radiotherapy and radioprotection. Their persistence in the progeny of normal cells may contribute to risk of long-term radiation-related health effect in human, including cancer. Hence, this study investigates the role of gap junction intercellular communication (GJIC) and the quality of radiation in the propagation of stressful effects in the unirradiated bystander cells and their progeny. Material and methods: Human skin fibroblasts in the confluent state were exposed to microbeam irradiations with different linear energy transfer (LET) at mean absorbed dose of 0.4 Gy, in the presence or absence of GJIC inhibitor (AGA) by which 0.036-0.4% of cells were directly targeted by IR. After 4 h irradiation or following 20 population doublings, the cells were harvested and assayed for micronucleus (MN) formation, gene mutation and protein oxidation. Results: Our results showed that high-LET carbon microbeams (LET ∼103 keV/μm) and high-LET proton microbeams (LET ∼11 keV/μm) were more effective than low-LET X ray microbeam (LET ∼6 keV/μm) in the induction of DNA damage (MN formation) in bystander cells. Interestingly, significant attenuation of MN formation occurred in bystander cells in the presence of AGA after proton and carbon microbeams. In contrast, incubation of the cells with AGA did not significantly affect the induction of MN formation in bystander cells during confluent holding after X irradiation. Further, the progeny of bystander cells exposed to X rays or protons showed persistent oxidative stress which correlated MN formation and mutation frequency. Such effects were not observed after irradiation by carbon ions. Importantly, the progeny of bystander cells from cultures exposed to protons or carbon ions under conditions where GJIC was inhibited harbored reduced oxidative and genetic damage. This mitigating effect was not detected when the cultured were exposed to X rays. Taken together, the overall results show the expression of stressful effects in the bystander cells and their progeny are dependent on the radiation quality or LET. Conclusions: Our findings suggest that the involvement of GJIC-dependent of radiation quality in the propagation of radiation induces stressful effects to bystander cells and their progeny. In addition, this work provides a strong support to the fact that carbon ions can significantly reduce the risk of cancer and have potential implications in the therapeutic outcome of radiotherapy compared to X rays or protons. Citation Format: Narongchai Autsavapromporn, Ianik Plante, Cuihua Liu, Teruaki Konishi, Noriko Usami, Tomoo Funayama, Yukio Uchihori, Tom K. Hei, Edouard I. Azzam, Sirikan Yamada, Takeshi Murakami, Masao Suzuki. Bystander effect and genomic instability in human cells and their progeny after irradiation with X rays, protons or carbon ions: role of gap junction communication. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1815. doi:10.1158/1538-7445.AM2015-1815