Presentation Genetic Changes in Progeny of Bystander Human Fibroblasts After Microbeam Irradiation with X Rays, Protons or Carbon Ions: The Relevance to Cancer Risk

Autsavapromporn, Narongchai  ,  Plante, Ianik  ,  hua Liu, Chi  ,  Konishi, Teruaki  ,  Usami, Noriko  ,  Funayama, Tomoo  ,  Uchihori, Yukio  ,  K. Hei, Tom  ,  I Azzam, Edouard  ,  Murakami, Takeshi  ,  Suzuki, Masao

Purpose: Radiation-induced bystander effects and genomic instability have important implication in radiotherapy and radioprotection. Their persistence in normal cells may contribute to risk of long-term health effects of radiation, including cancer. This study investigates the role of gap junction intercellular communication (GJIC) and radiation quality in the propagation of stressful effects in the bystander cells and their progeny.Material and methods: Confluent human skin fibroblasts 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 radiation. 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/um) and high-LET proton microbeams (LET ~11 keV/um) were more effective than low-LET X ray microbeam (LET ~6 keV/um) in the induction 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. Furthermore, 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 expression of stressful effects in the bystander cells and their progeny are dependent on the radiation quality or LET.Conclusions: These finding suggest that the involvement of GJIC in the propagation of radiation-induced stress to bystander cells and their progeny. In addition, our results provide strong support for carbon ions can reduce the risk of lesions associated with cancer.
15th International Congress of Radiation Research

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