Role of gap junctional intercellular communication in radiation-induced bystander effects in human fibroblasts.
Involvement of gap junctional intercellular communication (GJIC) in bystander responses of confluent human fibroblasts irradiated with a carbon-ion beam was investigated. It was found that the lower the radiation dose, the higher the yield of radiation-induced micronuclei per nuclear traversal, suggesting the existence of bystander effects. This low-dose sensitivity was increased when GJIC was enhanced by treating cells with 8-Br-cAMP, but it was partly reduced by treating cells with DMSO, an effective scavenger of reactive oxygen species (ROS). Moreover, no low-dose sensitivity was observed when cells were treated with 100 micro M lindane, an inhibitor of GJIC. The survival of irradiated cells was increased by DMSO but was not influenced significantly by cAMP or lindane. On the other hand, G(1)-phase arrest was detected in the irradiated cells, and it was enhanced by cAMP. In contrast, this arrest was reduced or almost eliminated by DMSO or lindane, respectively, even when cells were irradiated with such a high dose that each cell received five nuclear traversals on average. Thus the bystander responses occurred after both low-dose and relatively high-dose irradiation. Our results indicated that both GJIC and ROS contributed to the radiation-induced bystander effect, but gap junctional channels might play an essential role by modulating the release of radiation-induced signaling factors.
Shao
Chunlin
C
Heavy-Ion Radiobiology Research Group, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
Furusawa
Yoshiya
Y
Aoki
Mizuho
M
Ando
Koichi
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism; D024201:Bystander Effect / Q000528:radiation effects*; D002453:Cell Cycle / Q000528:radiation effects; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D000242:Cyclic AMP / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D005456:Fluorescent Dyes / Q000494:pharmacology; D017629:Gap Junctions / Q000502:physiology*; D001556:Hexachlorocyclohexane / Q000494:pharmacology; D006801:Humans; D007365:Intercellular Junctions / Q000528:radiation effects*; D007546:Isoquinolines / Q000494:pharmacology; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects*; D017382:Reactive Oxygen Species
D005456:Fluorescent Dyes; D007546:Isoquinolines; D017382:Reactive Oxygen Species; D015124:8-Bromo Cyclic Adenosine Monophosphate; D001556:Hexachlorocyclohexane; C017475:lucifer yellow; D000242:Cyclic AMP; D004121:Dimethyl Sulfoxide