
Heavy‐ion‐induced bystander killing of human lung cancer cells: Role of gap junctional intercellular communication
Author(s) -
Harada Kosaku,
aka Tetsuo,
Hamada Nobuyuki,
Sakurai Hideyuki,
Hasegawa Masatoshi,
Funayama Tomoo,
Kakizaki Takehiko,
Kobayashi Yasuhiko,
Nakano Takashi
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01093.x
Subject(s) - bystander effect , clonogenic assay , intracellular , cell , gap junction , cancer cell , programmed cell death , microbiology and biotechnology , irradiation , a549 cell , population , cell growth , chemistry , biology , biophysics , cancer research , medicine , immunology , cancer , apoptosis , biochemistry , genetics , environmental health , physics , nuclear physics
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 carbon ions (220 MeV), 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 they 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 bystander responses. ( Cancer Sci 2009; 100: 684–688)