PMID- 23987132 OWN - NLM STAT- MEDLINE DCOM- 20131212 LR - 20240321 IS - 1938-5404 (Electronic) IS - 0033-7587 (Print) IS - 0033-7587 (Linking) VI - 180 IP - 4 DP - 2013 Oct TI - Gap junction communication and the propagation of bystander effects induced by microbeam irradiation in human fibroblast cultures: the impact of radiation quality. PG - 367-75 LID - 10.1667/RR3111.1 [doi] AB - 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/mum), 18.3 MeV/u carbon ion (LET ~103 keV/mum), 13 MeV/u neon ion (LET ~380 keV/mum) or 11.5 MeV/u argon ion (LET ~1,260 keV/mum) microbeams in the presence or absence of 18-alpha-glycyrrhetinic acid (AGA), an inhibitor of GJIC. After 4 h incubation at 37 degrees 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. FAU - Autsavapromporn, Narongchai AU - Autsavapromporn N AD - a Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, 263-8555, Japan. FAU - Suzuki, Masao AU - Suzuki M FAU - Funayama, Tomoo AU - Funayama T FAU - Usami, Noriko AU - Usami N FAU - Plante, Ianik AU - Plante I FAU - Yokota, Yuichiro AU - Yokota Y FAU - Mutou, Yasuko AU - Mutou Y FAU - Ikeda, Hiroko AU - Ikeda H FAU - Kobayashi, Katsumi AU - Kobayashi K FAU - Kobayashi, Yasuhiko AU - Kobayashi Y FAU - Uchihori, Yukio AU - Uchihori Y FAU - Hei, Tom K AU - Hei TK FAU - Azzam, Edouard I AU - Azzam EI FAU - Murakami, Takeshi AU - Murakami T LA - eng GR - P01 CA049062/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130829 PL - United States TA - Radiat Res JT - Radiation research JID - 0401245 SB - IM MH - Bystander Effect/*radiation effects MH - Cells, Cultured MH - DNA Damage MH - Dose-Response Relationship, Radiation MH - Fibroblasts/*cytology/*radiation effects MH - Gap Junctions/*radiation effects MH - Humans MH - Linear Energy Transfer MH - Monte Carlo Method PMC - PMC4058832 MID - NIHMS584046 EDAT- 2013/08/31 06:00 MHDA- 2013/12/18 06:00 PMCR- 2014/06/16 CRDT- 2013/08/31 06:00 PHST- 2013/08/31 06:00 [entrez] PHST- 2013/08/31 06:00 [pubmed] PHST- 2013/12/18 06:00 [medline] PHST- 2014/06/16 00:00 [pmc-release] AID - 10.1667/RR3111.1 [doi] PST - ppublish SO - Radiat Res. 2013 Oct;180(4):367-75. doi: 10.1667/RR3111.1. Epub 2013 Aug 29.