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重新评估新范式和现代分子研究的线性无阈(LNT)模型。

Re-evaluation of the linear no-threshold (LNT) model using new paradigms and modern molecular studies.

机构信息

Northern Ontario School of Medicine, Laurentian University, 935 Ramsey Lake Rd, Sudbury, ON, P3E 2C6, Canada.

Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main Street W, Hamilton ON, L8S 4K1, Canada.

出版信息

Chem Biol Interact. 2019 Mar 1;301:54-67. doi: 10.1016/j.cbi.2018.11.013. Epub 2019 Feb 11.

Abstract

The linear no-threshold (LNT) model is currently used to estimate low dose radiation (LDR) induced health risks. This model lacks safety thresholds and postulates that health risks caused by ionizing radiation is directly proportional to dose. Therefore even the smallest radiation dose has the potential to cause an increase in cancer risk. Advances in LDR biology and cell molecular techniques demonstrate that the LNT model does not appropriately reflect the biology or the health effects at the low dose range. The main pitfall of the LNT model is due to the extrapolation of mutation and DNA damage studies that were conducted at high radiation doses delivered at a high dose-rate. These studies formed the basis of several outdated paradigms that are either incorrect or do not hold for LDR doses. Thus, the goal of this review is to summarize the modern cellular and molecular literature in LDR biology and provide new paradigms that better represent the biological effects in the low dose range. We demonstrate that LDR activates a variety of cellular defense mechanisms including DNA repair systems, programmed cell death (apoptosis), cell cycle arrest, senescence, adaptive memory, bystander effects, epigenetics, immune stimulation, and tumor suppression. The evidence presented in this review reveals that there are minimal health risks (cancer) with LDR exposure, and that a dose higher than some threshold value is necessary to achieve the harmful effects classically observed with high doses of radiation. Knowledge gained from this review can help the radiation protection community in making informed decisions regarding radiation policy and limits.

摘要

线性无阈(LNT)模型目前用于估计低剂量辐射(LDR)引起的健康风险。该模型缺乏安全阈值,并假设电离辐射引起的健康风险与剂量成正比。因此,即使是最小的辐射剂量也有可能增加癌症风险。LDR 生物学和细胞分子技术的进步表明,LNT 模型不能恰当地反映低剂量范围内的生物学或健康效应。LNT 模型的主要缺陷是由于在高剂量率下进行的高剂量辐射的突变和 DNA 损伤研究的推断。这些研究构成了几个过时的范例的基础,这些范例要么是不正确的,要么不适用于 LDR 剂量。因此,本综述的目的是总结 LDR 生物学中的现代细胞和分子文献,并提供更好地代表低剂量范围内生物学效应的新范例。我们证明,LDR 激活了多种细胞防御机制,包括 DNA 修复系统、程序性细胞死亡(细胞凋亡)、细胞周期停滞、衰老、适应性记忆、旁观者效应、表观遗传学、免疫刺激和肿瘤抑制。本综述中提出的证据表明,LDR 暴露的健康风险(癌症)极小,只有高于某个阈值的剂量才会产生经典上观察到的高剂量辐射的有害效应。从本综述中获得的知识可以帮助辐射防护界就辐射政策和限制做出明智的决策。

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