Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4K1.
Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4K1.
J Environ Radioact. 2014 Jul;133:5-9. doi: 10.1016/j.jenvrad.2013.04.002. Epub 2013 May 10.
The last 20 years have seen a major paradigm shift in radiation biology. Several discoveries challenge the DNA centric view which holds that DNA damage is the critical effect of radiation irrespective of dose. This theory leads to the assumption that dose and effect are simply linked - the more energy deposition, the more DNA damage and the greater the biological effect. This is embodied in radiation protection (RP) regulations as the linear-non-threshold (LNT) model. However the science underlying the LNT model is being challenged particularly in relation to the environment because it is now clear that at low doses of concern in RP, cells, tissues and organisms respond to radiation by inducing responses which are not readily predictable by dose. These include adaptive responses, bystander effects, genomic instability and low dose hypersensitivity, and are commonly described as stress responses, while recognizing that "stress" can be good as well as bad. The phenomena contribute to observed radiation responses and appear to be influenced by genetic, epigenetic and environmental factors, meaning that dose and response are not simply related. The question is whether our discovery of these phenomena means that we need to re-evaluate RP approaches. The so-called "non-targeted" mechanisms mean that low dose radiobiology is very complex and supra linear or sub-linear (even hormetic) responses are possible but their occurrence is unpredictable for any given system level. Issues which may need consideration are synergistic or antagonistic effects of other pollutants. RP, at present, only looks at radiation dose but the new (NTE) radiobiology means that chemical or physical agents, which interfere with tissue responses to low doses of radiation, could critically modulate the predicted risk. Similarly, the "health" of the organism could determine the effect of a given low dose by enabling or disabling a critical response. These issues will be discussed.
过去 20 年来，放射生物学发生了重大的范式转变。有几项发现挑战了以 DNA 为中心的观点，该观点认为，无论剂量如何，DNA 损伤都是辐射的关键效应。这一理论导致了这样的假设，即剂量和效应是简单相关的——能量沉积越多，DNA 损伤越大，生物效应越大。这体现在放射防护（RP）法规中的线性非阈值（LNT）模型中。然而，LNT 模型的基础科学正受到挑战，特别是在与环境有关的方面，因为现在很明显，在 RP 中关注的低剂量下，细胞、组织和生物体通过诱导不易通过剂量预测的反应来对辐射作出反应。这些反应包括适应性反应、旁观者效应、基因组不稳定性和低剂量超敏反应，通常被描述为应激反应，同时认识到“应激”既可以是好的，也可以是坏的。这些现象促成了观察到的辐射反应，并似乎受到遗传、表观遗传和环境因素的影响，这意味着剂量和反应并不简单相关。问题是，我们对这些现象的发现是否意味着我们需要重新评估 RP 方法。所谓的“非靶向”机制意味着低剂量放射生物学非常复杂，可能会出现超线性或亚线性（甚至是激素样）反应，但对于任何给定的系统水平，其发生都是不可预测的。需要考虑的问题是其他污染物的协同或拮抗效应。目前，RP 只考虑辐射剂量，但新的（NTE）放射生物学意味着，干扰组织对低剂量辐射反应的化学或物理剂，可能会严重调节预测的风险。同样，生物体的“健康”状况可以通过使或不使关键反应失效来决定给定低剂量的效应。这些问题将被讨论。
