Participation of gap junction communication in potentially lethal damage repair and DNA damage in human fibroblasts exposed to low- or high-LET radiation.
Participation of gap junction communication in potentially lethal damage repair and DNA damage in human fibroblasts exposed to low- or high-LET radiation.
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DOI：
10.1016/j.mrgentox.2013.07.001
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发表时间：
2013-08-30
影响因子：
1.9
通讯作者：
Murakami, Takeshi
中科院分区：
文献类型：
--
作者：
Autsavapromporn, Narongchai;Suzuki, Masao;Plante, Ianik;Liu, Cuihua;Uchihori, Yukio;Hei, Tom K.;Azzam, Edouard I.;Murakami, Takeshi
关键词：
现有的研究还没有完全解释不同类型的电离辐射（IR）如何调节细胞群或组织的反应。在我们以前的工作中，我们表明，间隙连接细胞间通讯（GJIC）介导的高线性能量转移（LET）辐射，其中几乎每个细胞都是由IR轨道穿过照射细胞之间的传播的压力效应。在本研究中，我们对GJIC在调节暴露于低或高LET IR的细胞中潜在致死性损伤（PLDR）修复和微核形成中的作用进行了深入研究。将汇合的人成纤维细胞在存在或不存在间隙连接抑制剂的情况下暴露于200 kV X射线（LET ≤ 1.7 keV/µm）、碳离子（LET ≤ 76 keV/µm）、硅离子（LET ≤ 113 keV/µm）或铁离子（LET ≤ 400 keV/µm）。将成纤维细胞在37 °C下孵育不同时间。正如预期的那样，高LET IR比低LET X射线在照射后不久杀死细胞和破坏DNA更有效。然而，当细胞在融合状态下保持数小时时，PLDR与DNA损伤的减少相关，仅发生在暴露于X射线的细胞中。有趣的是，GJIC的抑制消除了毒性作用的增强，这导致暴露于高，实验表明，间隙连接通讯在暴露于高LET IR的辐射细胞中的应激效应传播中起重要作用。而GJIC在低LET照射后对PLDR和DNA损伤仅具有最小的影响。总之，我们的研究结果表明，PLDR和诱导DNA损伤显然取决于间隙连接通信和辐射质量。
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 200 kV X rays (LET ∼ 1.7 keV/µm), carbon ions (LET ∼ 76 keV/µm), silicon ions (LET ∼ 113 keV/µm) or iron ions (LET ∼ 400 keV/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.
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影响因子：
2.6
作者：
GOODHEAD, DT
通讯作者：
GOODHEAD, DT
影响因子：
2
作者：
Autsavapromporn N;De Toledo SM;Buonanno M;Jay-Gerin JP;Harris AL;Azzam EI
通讯作者：
Azzam EI
影响因子：
2.6
作者：
GOODHEAD, DT;MUNSON, RJ;COX, R
通讯作者：
COX, R
影响因子：
3.4
作者：
ELKIND, MM
通讯作者：
ELKIND, MM
DOI：
10.1073/pnas.011417098
发表时间：
2001-01-16
影响因子：
11.1
作者：
Azzam, EI;de Toledo, SM;Little, JB
通讯作者：
Little, JB