Presentation Late Effects in the Progeny of Bystander Human Cells are Dependent on Radiation Quality: The Relevance to Cancer Risk

Autsavapromporn, Narongchai  ,  Plante, Ianik  ,  hua Liu, Cui  ,  Konishi, Teruaki  ,  Usami, Noriko  ,  Funayama, Tomoo  ,  I. Azzam, Edouard  ,  Murakami, Takeshi  ,  Suzuki, Masao

Purpose: Considerable evidence exists regarding ionizing radiation (IR) induced bystander effect has important implication in clinical radiotherapy [1]. Their persistence in the progeny of human cells may contribute to risk of long-term radiation-related human health effect, including cancer [2]. The objective of this study is to elucidate the involvement of radiation quality and gap junction intercellular communication (GJIC) in the propagation of delayed stressful effects in the progeny of bystander normal human cells. Materials and method: Confluent human skin fibroblasts (NB1RGB) were exposed to various types of microbeam with a different linear energy transfer (LET) at mean absorbed doses 0.4 Gy, wherein 0.036-0.4% of the cells were targeted by IR. Following 20 populations post-irradiation, the cells were harvested and assayed for micronucleus formation, mutation assay and protein oxidation. Results: Our results showed that the delayed stressful effects in the progeny of bystander cells are dependent on radiation quality or LET. The progeny of bystander cells exposed to X rays (LET ~6 keV/µm) and protons (LET ~11 keV/µm) showed the persistence of oxidative stress, and correlate with the increased micronucleus formation and mutant fraction. However, such effects were not observed after irradiation by carbon ions (LET~103 keV/µm). Interestingly, inhibition of GJIC mitigated the damaging effects in the progeny of bystander cells exposed to protons and carbon ions but not X rays. Conclusions: These data show, for the first time, carbon ions can reduce cancer risk after microbeam irradiation compared with X rays or protons, and GJIC may be a critical mediator in the observed effect.
The 12th International Workshop on Microbeam Probes of Cellular Radiation Response

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