title: Heavy-ion-induced bystander killing of human lung cancer cells: role of gap junctional intercellular communication.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. kusauko@showa.gunma-u.ac.jp
authors.forename: Kosaku
authors.initials: K
authors.lastname: Harada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nonaka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamada
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Tomoo
authors.initials: T
authors.lastname: Funayama
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kakizaki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D024201:Bystander Effect / Q000528:radiation effects*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D004307:Dose-Response Relationship, Radiation; D017629:Gap Junctions / Q000502:physiology*; D020450:Heavy Ions; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology