Intercellular and Intracellular Signaling Pathways Mediating Ionizing Radiation-Induced Bystander Effects

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  • HAMADA Nobuyuki
    Department of Quantum Biology, Division of Bioregulatory Medicine, Gunma University Graduate School of Medicine The 21st Century Center of Excellence (COE) Program for Biomedical Research Using Accelerator Technology Microbeam Radiation Biology Group, Radiation-Applied Biology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency (JAEA)
  • MATSUMOTO Hideki
    Division of Oncology, Biomedical Imaging Research Center, University of Fukui
  • HARA Takamitsu
    Department of Quantum Biology, Division of Bioregulatory Medicine, Gunma University Graduate School of Medicine The 21st Century Center of Excellence (COE) Program for Biomedical Research Using Accelerator Technology Microbeam Radiation Biology Group, Radiation-Applied Biology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency (JAEA)
  • KOBAYASHI Yasuhiko
    Department of Quantum Biology, Division of Bioregulatory Medicine, Gunma University Graduate School of Medicine The 21st Century Center of Excellence (COE) Program for Biomedical Research Using Accelerator Technology Microbeam Radiation Biology Group, Radiation-Applied Biology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency (JAEA)

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Abstract

A rapidly growing body of experimental evidence indicates that ionizing radiation induces biological effects in non-irradiated bystander cells that have received signals from adjacent or distant irradiated cells. This phenomenon, which has been termed the ionizing radiation-induced bystander effect, challenges the long-standing paradigm that radiation traversal through the nucleus of a cell is a prerequisite to elicit genetic damage or a biological response. Bystander effects have been observed in a number of experimental systems, and cells whose nucleus or cytoplasm is irradiated exert bystander responses. Bystander cells manifest a multitude of biological consequences, such as genetic and epigenetic changes, alterations in gene expression, activation of signal transduction pathways, and delayed effects in their progeny. Several mediating mechanisms have been proposed. These involve gap junction-mediated intercellular communication, secreted soluble factors, oxidative metabolism, plasma membrane-bound lipid rafts, and calcium fluxes. This paper reviews briefly the current knowledge of the bystander effect with a focus on proposed mechanisms. The potential benefit of bystander effects to cancer radiotherapy will also be discussed.<br>

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