Dynamics of cellular responses to radiation.
Dynamics of cellular responses to radiation.
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DOI：
10.1371/journal.pcbi.1003513
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发表时间：
2014-04
影响因子：
4.3
通讯作者：
Komarova NL
中科院分区：
文献类型：
--
作者：
Wodarz D;Sorace R;Komarova NL
了解暴露于低剂量电离辐射的后果是一个重要的公共卫生问题。虽然低剂量辐射的风险是根据线性非阈值模型根据高剂量数据进行外推估计的，但很明显，与高剂量辐射相比，低剂量辐射下的细胞反应可能有很大不同。这方面的重要现象包括辐射适应性反应以及低剂量超辐射敏感性（HRS）和增加的辐射抗性（IRR）。对于辐射适应性反应，低剂量暴露可以防止随后的挑战，并且已经提出了两种机制：细胞内机制，由于启动辐射而诱导细胞变化，以及通过细胞间通信诱导保护状态。我们使用数学模型来检验这些机制对细胞对低剂量辐射反应的影响。我们发现细胞内机制可以解释辐射适应性反应的发生。有趣的是，同样的机制也可以解释HRS和IRR现象的存在，并成功地描述了实验观察到的各种细胞类型的剂量-反应关系。这表明不同的、看似不相关的低剂量现象可能是由共同的核心过程连接和驱动的。关于细胞间通信机制，我们发现它也可以解释辐射适应性反应的发生，表明这方面的冗余。然而，该模型还表明，通信机制对于持续暴露于相对低水平辐射的细胞群体的长期生存至关重要，这是我们模型中的细胞内机制无法实现的。提出了解决我们的模型预测的实验测试。低剂量辐射对细胞和组织的影响是一个公共卫生问题，因为人类暴露于来自各种来源的低剂量电离辐射，如宇宙射线、土壤放射性、环境污染和各种医疗程序。在低剂量辐射下，可以观察到在高剂量下不会发生的现象，例如辐射适应反应以及低剂量超辐射敏感性（HRS）和辐射抗性增加（IRR），这些迄今尚未完全了解。这些现象都被分别研究过，并提出了具体的机制来解释它们。我们利用数学模型成功地拟合了各种条件下的实验数据，证明了关于细胞对低剂量辐射反应的一组基本假设和文献假设可以解释所有三种低剂量现象，表明它们是相互关联的。根据该模型，这些现象是由构成相关细胞种群动态基础的多因素相互作用造成的，这为了解这些反应和评估低剂量辐射暴露对人类健康造成的风险提供了一个新的框架。
Understanding the consequences of exposure to low dose ionizing radiation is an important public health concern. While the risk of low dose radiation has been estimated by extrapolation from data at higher doses according to the linear non-threshold model, it has become clear that cellular responses can be very different at low compared to high radiation doses. Important phenomena in this respect include radioadaptive responses as well as low-dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR). With radioadaptive responses, low dose exposure can protect against subsequent challenges, and two mechanisms have been suggested: an intracellular mechanism, inducing cellular changes as a result of the priming radiation, and induction of a protected state by inter-cellular communication. We use mathematical models to examine the effect of these mechanisms on cellular responses to low dose radiation. We find that the intracellular mechanism can account for the occurrence of radioadaptive responses. Interestingly, the same mechanism can also explain the existence of the HRS and IRR phenomena, and successfully describe experimentally observed dose-response relationships for a variety of cell types. This indicates that different, seemingly unrelated, low dose phenomena might be connected and driven by common core processes. With respect to the inter-cellular communication mechanism, we find that it can also account for the occurrence of radioadaptive responses, indicating redundancy in this respect. The model, however, also suggests that the communication mechanism can be vital for the long term survival of cell populations that are continuously exposed to relatively low levels of radiation, which cannot be achieved with the intracellular mechanism in our model. Experimental tests to address our model predictions are proposed. The effect of low-dose radiation on cells and tissues is a public health concern, because the human population is exposed to low-dose ionizing radiation coming from a variety of sources, such as cosmic rays, soil radioactivity, environmental contaminations, and various medical procedures. At low doses of radiation, phenomena are observed that do not occur at higher doses, such as radioadaptive responses as well as low-dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR), which are so far not fully understood. Each of these phenomena have been investigated separately, and specific mechanisms have been suggested to explain them. Using mathematical models that are successfully fitted to experimental data under a variety of conditions, we show that a set of basic and documented assumptions about cellular responses to low-dose radiation can explain all three low-dose phenomena, indicating that they are inter-related. According to the model, these phenomena are brought about by the multi-factorial interactions that underlie the population dynamics of the cells involved, and this provides a new framework to understand these responses, and to evaluate the risk to human health posed by exposure to low-dose radiation.
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影响因子：
3.4
作者：
JOINER, MC;JOHNS, H
通讯作者：
JOHNS, H
DOI：
10.1073/pnas.0830918100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Rothkamm, K;Löbrich, M
通讯作者：
Löbrich, M
影响因子：
3.4
作者：
Chang, CC;Sun, W;Trosko, JE
通讯作者：
Trosko, JE
DOI：
10.2187/bss.18.247
发表时间：
2004-12-01
期刊：
Uchu Seibutsu Kagaku
影响因子：
--
作者：
Matsumoto, Hideki;Takahashi, Akihisa;Ohnishi, Takeo
通讯作者：
Ohnishi, Takeo
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