Intercellular communication amplifies stressful effects in high-charge, high-energy (HZE) particle-irradiated human cells.
Intercellular communication amplifies stressful effects in high-charge, high-energy (HZE) particle-irradiated human cells.
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DOI：
10.1269/jrr.10114
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发表时间：
2011
影响因子：
2
通讯作者：
Azzam EI
中科院分区：
文献类型：
--
作者：
Autsavapromporn N;De Toledo SM;Buonanno M;Jay-Gerin JP;Harris AL;Azzam EI
了解粒子辐射生物效应的机制对于空间探索和放射治疗至关重要。在这里，我们研究了间隙连接细胞间通讯（GJIC）在调节融合培养物中诱导的有害效应中的作用，其中大多数细胞被一个或多个辐射轨道穿过。我们专注于辐射质量（线性能量转移; LET）的影响，在受照射的细胞之间的DNA损伤和细胞死亡的交界处传播。将融合的正常人成纤维细胞暴露于分级剂量的1 GeV质子（LET ~0.2 keV/μm）或1 GeV/u铁离子（LET ~151 keV/μm），并在照射后不久和较长的孵育期后测定克隆存活率和微核形成，这是DNA损伤的反映。当在照射后5-10分钟内测定时，铁离子在杀死暴露培养物中90%的细胞方面比质子有效约2.7倍。当细胞在照射后保持融合状态数小时时，潜在致死性损伤（PLDR）的实质性修复，加上微核形成的减少，发生在暴露于质子的细胞中，而不是暴露于铁离子的细胞中。事实上，在暴露于类似毒性剂量的铁离子后，这种汇合保持增强了诱导的毒性作用。然而，在铁离子照射后，18-α-大黄酸对GJIC的抑制消除了增强的毒性，并将微核形成降低至低于照射后不久在细胞中检测到的水平。数据显示，低LET辐射在数小时内诱导强烈的PLDR，但具有类似即时毒性的高LET辐射不会诱导PLDR，并且其毒性在照射后随时间增加。结果还表明，GJIC之间的照射细胞放大应激效应后，暴露于高，但不是LET辐射，和GJIC只有最小的影响，细胞恢复低LET辐射。
Understanding the mechanisms that underlay the biological effects of particulate radiations is essential for space exploration and for radiotherapy. Here, we investigated the role of gap junction intercellular communication (GJIC) in modulating harmful effects induced in confluent cultures wherein most cells are traversed by one or more radiation tracks. We focused on the effect of radiation quality (linear energy transfer; LET) on junctional propagation of DNA damage and cell death among the irradiated cells. Confluent normal human fibroblasts were exposed to graded doses of 1 GeV protons (LET ~0.2 keV/μm) or 1 GeV/u iron ions (LET ~151 keV/μm) and were assayed for clonogenic survival and for micronucleus formation, a reflection of DNA damage, shortly after irradiation and following longer incubation periods. Iron ions were ~2.7 fold more effective than protons at killing 90% of the cells in the exposed cultures when assayed within 5–10 minutes after irradiation. When cells were held in the confluent state for several hours after irradiation, substantial repair of potentially lethal damage (PLDR), coupled with a reduction in micronucleus formation, occurred in cells exposed to protons, but not in those exposed to iron ions. In fact, such confluent holding after exposure to a similarly toxic dose of iron ions enhanced the induced toxic effect. However, following iron ion irradiation, inhibition of GJIC by 18-α-glycyrrhetinic acid eliminated the enhanced toxicity and reduced micronucleus formation to levels below those detected in cells assayed shortly after irradiation. The data show that low LET radiation induces strong PLDR within hours, but that high LET radiation with similar immediate toxicity does not induce PLDR and its toxicity increases with time following irradiation. The results also show that GJIC among irradiated cells amplifies stressful effects following exposure to high, but not LET radiation, and that GJIC has only minimal effect on cellular recovery following low LET irradiation.
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影响因子：
3.5
作者：
Jiang, HY;Wang, B;Paganetti, H
通讯作者：
Paganetti, H
DOI：
10.1016/0165-1161(85)90015-9
发表时间：
1985-01-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
FENECH, M;MORLEY, AA
通讯作者：
MORLEY, AA
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
影响因子：
4.1
作者：
Koreen, IV;Elsayed, WA;Harris, AL
通讯作者：
Harris, AL
影响因子：
5.7
作者：
Harada, Kosaku;Nonaka, Tetsuo;Nakano, Takashi
通讯作者：
Nakano, Takashi