RRC ID 44616
著者 Autsavapromporn N, Suzuki M, Funayama T, Usami N, Plante I, Yokota Y, Mutou Y, Ikeda H, Kobayashi K, Kobayashi Y, Uchihori Y, Hei TK, Azzam EI, Murakami T.
タイトル Gap junction communication and the propagation of bystander effects induced by microbeam irradiation in human fibroblast cultures: the impact of radiation quality.
ジャーナル Radiat Res
Abstract Understanding the mechanisms underlying the bystander effects of low doses/low fluences of low- or high-linear energy transfer (LET) radiation is relevant to radiotherapy and radiation protection. Here, we investigated the role of gap-junction intercellular communication (GJIC) in the propagation of stressful effects in confluent normal human fibroblast cultures wherein only 0.036-0.144% of cells in the population were traversed by primary radiation tracks. Confluent cells were exposed to graded doses from monochromatic 5.35 keV X ray (LET ~6 keV/μm), 18.3 MeV/u carbon ion (LET ~103 keV/μm), 13 MeV/u neon ion (LET ~380 keV/μm) or 11.5 MeV/u argon ion (LET ~1,260 keV/μm) microbeams in the presence or absence of 18-α-glycyrrhetinic acid (AGA), an inhibitor of GJIC. After 4 h incubation at 37°C, the cells were subcultured and assayed for micronucleus (MN) formation. Micronuclei were induced in a greater fraction of cells than expected based on the fraction of cells targeted by primary radiation, and the effect occurred in a dose-dependent manner with any of the radiation sources. Interestingly, MN formation for the heavy-ion microbeam irradiation in the absence of AGA was higher than in its presence at high mean absorbed doses. In contrast, there were no significant differences in cell cultures exposed to X-ray microbeam irradiation in presence or absence of AGA. This showed that the inhibition of GJIC depressed the enhancement of MN formation in bystander cells from cultures exposed to high-LET radiation but not low-LET radiation. Bystander cells recipient of growth medium harvested from 5.35 keV X-irradiated cultures experienced stress manifested in the form of excess micronucleus formation. Together, the results support the involvement of both junctional communication and secreted factor(s) in the propagation of radiation-induced stress to bystander cells. They highlight the important role of radiation quality and dose in the observed effects.
巻・号 180(4)
ページ 367-75
公開日 2013-10-1
DOI 10.1667/RR3111.1
PMID 23987132
PMC PMC4058832
MeSH Bystander Effect / radiation effects* Cells, Cultured DNA Damage Dose-Response Relationship, Radiation Fibroblasts / cytology* Fibroblasts / radiation effects* Gap Junctions / radiation effects* Humans Linear Energy Transfer Monte Carlo Method
IF 2.657
引用数 45
WOS 分野 BIOLOGY RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING BIOPHYSICS
リソース情報
ヒト・動物細胞 NB1RGB(RCB0222)