title: Participation of gap junction communication in potentially lethal damage repair and DNA damage in human fibroblasts exposed to low- or high-LET radiation.
abstract: Existing research has not fully explained how different types of ionizing radiation (IR) modulate the responses of cell populations or tissues. In our previous work, we showed that gap junction intercellular communication (GJIC) mediates the propagation of stressful effects among irradiated cells exposed to high linear energy transfer (LET) radiations, in which almost every cells is traversed by an IR track. In the present study, we conducted an in-depth study of the role of GJIC in modulating the repair of potentially lethal damage (PLDR) and micronuclei formation in cells exposed to low- or high-LET IR. Confluent human fibroblasts were exposed in the presence or absence of a gap junction inhibitor to 200kV X rays (LET∼1.7keV/μm), carbon ions (LET∼76keV/μm), silicon ions (LET∼113keV/μm) or iron ions (LET∼400keV/μm) that resulted in isosurvival levels. The fibroblasts were incubated for various times at 37°C. As expected, high-LET IR were more effective than were low-LET X rays at killing cells and damaging DNA shortly after irradiation. However, when cells were held in a confluent state for several hours, PLDR associated with a reduction in DNA damage, occurred only in cells exposed to X rays. Interestingly, inhibition of GJIC eliminated the enhancement of toxic effects, which resulted in an increase of cell survival and reduction in the level of micronucleus formation in cells exposed to high, but not in those exposed to low-LET IR. The experiment shows that gap-junction communication plays an important role in the propagation of stressful effects among irradiated cells exposed to high-LET IR while GJIC has only a minimal effect on PLDR and DNA damage following low-LET irradiation. Together, our results show that PLDR and induction of DNA damage clearly depend on gap-junction communication and radiation quality.
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Narongchai
authors.initials: N
authors.lastname: Autsavapromporn
authors.forename: Masao
authors.initials: M
authors.lastname: Suzuki
authors.forename: Ianik
authors.initials: I
authors.lastname: Plante
authors.forename: Cuihua
authors.initials: C
authors.lastname: Liu
authors.forename: Yukio
authors.initials: Y
authors.lastname: Uchihori
authors.forename: Tom K
authors.initials: TK
authors.lastname: Hei
authors.forename: Edouard I
authors.initials: EI
authors.lastname: Azzam
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murakami
mesh_terms: D002450:Cell Communication / Q000502:physiology / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D017629:Gap Junctions / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D018499:Linear Energy Transfer; D015162:Micronucleus Tests; D014965:X-Rays
keywords: Gap junction intercellular communication; Heavy-ion beams; Ionizing radiation; Linear energy transfer; Potentially lethal damage repair