Distinct response of irradiated and bystander fibroblasts to heavy-ion radiation

Hamada, Nobuyuki*; Ni, M.; Iwakawa, Mayumi*; Imadome, Kaori*; Funayama, Tomoo; Sakashita, Tetsuya; Sora, Sakura*; Imai, Takashi*; Kobayashi, Yasuhiko

Considering that less irradiated cells should coexist with more bystander cells in a population exposed to a lower dose of heavy ions, a clarification of the effects arising not only in irradiated cells but in their bystander cells would be crucial to comprehend the mechanism of action of heavy ions. Herein we have investigated heavy ion-induced bystander response in a situation whereby 0.0003% of cells in a confluent human fibroblast population were targeted using precise microbeams. Conventional broadfield irradiation was conducted in parallel to see the effects in irradiated cells. Intriguingly, bystander cells manifested a more transient apoptotic response and delayed p53 phosphorylation, compared with irradiated cells. Taken together, nearly three quarters of the genes whose expression changed in bystander cells were downregulated, and most of the genes upregulated in irradiated cells were downregulated in bystander cells. These findings highlight the distinct response of irradiated and bystander cells. Furthermore, interleukin genes were upregulated in irradiated cells whereas its receptor gene was upregulated in bystander cells, suggestive of the signal transmission from irradiated to bystander cells. Collectively, these induced bystander responses might be a defensive mechanism that would avert or minimize further expansion of aberrant cells.