Heavy-ion-induced bystander killing of human lung cancer cells; Role of gap junctional intercellular communication

ヒト肺がん由来細胞における重イオン誘発バイスタンダー細胞死; ギャップジャンクションを介した細胞間情報伝達の役割

原田 耕作*; 野中 哲生*; 浜田 信行*; 桜井 英幸*; 長谷川 正俊*; 舟山 知夫; 柿崎 竹彦*; 小林 泰彦; 中野 隆史*

Harada, Kosaku*; Nonaka, Tetsuo*; Hamada, Nobuyuki*; Sakurai, Hideyuki*; Hasegawa, Masatoshi*; Funayama, Tomoo; Kakizaki, Takehiko*; Kobayashi, Yasuhiko; Nakano, Takashi*

The aim of the present study was to clarify the mechanisms of cell death induced by heavy-ion irradiation focusing on the bystander effect in human lung cancer A549 cells. In microbeam irradiation, each of 1, 5 and 25 cells under confluent cell conditions was irradiated with 1, 5 or 10 particles of energetic carbon ions, and then the surviving fraction of the population was measured by a clonogenic assay in order to investigate the bystander effect of heavy-ions. In this experiment, the limited number of cells (0.0001-0.002%, 5-25 cells) under confluent cell conditions irradiated with 5 or 10 carbon ions resulted in an exaggerated 8-14% increase in cell death by clonogenic assay. However, these overshooting responses were not observed under exponentially growing cell conditions. Furthermore, these responses were inhibited in cells treated with an inhibitor of gap junctional intercellular communication (GJIC), whereas these were markedly enhanced by the addition of a stimulator of GJIC. The present results suggest that bystander cell killing by heavy-ions was induced mainly by direct cell-to-cell communication, such as GJIC, which might play important roles in the bystander responses.