Low dose, low-LET ionizing radiation-induced radioadaptation and associated early responses in unirradiated cells

Low dose, low-LET ionizing radiation-induced radioadaptation and associated early responses in unirradiated cells
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DOI:
10.1016/s0027-5107(02)00068-4
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发表时间:
2002-06-19
影响因子:
2.3
通讯作者:
Lehnert, BE
Lehnert, BE
中科院分区:
医学4区
文献类型:
--
作者:
Iyer, R;Lehnert, BE

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许多研究人员报告说,用低剂量的电离辐射(IR)照射细胞可以诱发放射抗性增强的情况,即放射适应性反应。在本报告中,我们研究了这样的假设:暴露于低剂量伽马射线的细胞上清液中存在的可传播因子可能在未受辐射的细胞中诱导放射适应性旁观者效应。用 1 cGy 剂量的伽马射线照射正常人肺成纤维细胞 (HFL-1),并将其上清液转移至未照射的 HFL-1 作为旁观者细胞模型。与直接照射的细胞相比,这种处理导致随后用 2 和 4 Gy 的伽马射线照射后克隆形成存活率增加。研究发现,这种放射适应性旁观者效应先于细胞内 TP53 蛋白水平的早期降低、细胞内 ROS 的增加以及氧化还原和 DNA 修复蛋白 AP 核酸内切酶 (APE) 的增加而发生。放射适应可以通过流体相、可转移因子在未照射细胞中发生的证明增加了目前对低剂量、低 LET IR 诱导放射适应反应机制的理解的复杂性。 (C) 2002 Elsevier Science B.V. 保留所有权利。
Numerous investigators have reported that irradiation of cells with a low dose of ionizing radiation (IR) can induce a condition of enhanced radioresistance, i.e. a radioadaptive response. In this report, we investigated the hypothesis that a radioadaptive bystander effect may be induced in unirradiated cells by a transmissible factor(s) present in the supernatants of cells exposed to low dose gamma-rays. Normal human lung fibroblasts (HFL-1) were irradiated with a 1 cGy dose of gamma-rays and their supernatants were transferred to unirradiated HFL-1 as a bystander cell model. Compared with the directly irradiated cells, such treatment resulted in increased clonogenic survival following subsequent gamma-irradiation with 2 and 4 Gy. This radioadaptive bystander effect was found to be preceded by early decreases in cellular levels of TP53 protein, increase in intracellular ROS, and increase in the redox and DNA repair protein AP-endonuclease (APE). The demonstration that radioadaptation can occur in unirradiated cells via a fluid-phase, transferable factor(s) adds to the complexity of the current understanding of mechanisms by which radioadaptive responses can be induced by low dose, low-LET IR. (C) 2002 Elsevier Science B.V. All rights reserved.