Heavy-ion microbeam irradiation induces bystander killing of human cells

Hamada, Nobuyuki*; Hara, Takamitsu*; Omura, Motoko*; Ni, M.*; Funayama, Tomoo; Sakashita, Tetsuya; Sora, Sakura*; Nakano, Takashi*; Kobayashi, Yasuhiko

Significant evidence indicates that ionizing radiation causes biological effects in nonirradiated bystander cells having received signals from directly irradiated cells. There is little information available hitherto as to the bystander effect of energetic heavy ions; however, our previous work has shown that in confluent cultures of normal human fibroblast AG01522 cells, targeted exposure of 0.0003% of cells to microbeams of 18.3 MeV/u C (103 keV/m) and 13.0 MeV/u Ne (375 keV/m) ions can similarly cause almost 10% decreases in the clonogenic survival, and twofold increments in the incidence of apoptosis whose temporal kinetics varies between irradiated and bystander cells. Using this experimental system, here we further report that bystander responses of AG01522 cells to 17.5 MeV/u 20Ne ions (294 keV/m) are consistent with those to 18.3 MeV/u C and 13.0 MeV/u Ne ions. We also demonstrate that such bystander-induced reductions in the survival are less pronounced and occur independently of Bcl-2 overexpression in human cervical cancer HeLa cells.