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Intercellular and intracellular signaling pathways mediating ionizing radiation-induced bystander effects

Hamada, Nobuyuki*; Matsumoto, Hideki*; Hara, Takamitsu*; Kobayashi, Yasuhiko

Experimental evidence has accumulated demonstrating that biological effects of ionizing radiation arise in non-irradiated bystander cells that have received signals from near or distant irradiated cells. This phenomenon has been termed the radiation-induced bystander effect and challenges the long-held tenet that cell nucleus is the quintessential target for radiation damage. Bystander effects encompass a range of endpoints, such as genetic and epigenetic alterations, changes in gene expression, signal transduction pathway activation, and late-arising effects in their descendants. Proposed mechanisms involve gap junctional cell-to-cell communication, transmissible soluble factors, oxidative stress, lipid rafts, and calcium fluxes. In this article, we review proposed mechanisms underpinning the bystander effect and also briefly discuss the potential benefit of bystander effects in cancer radiotherapy.

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