Lehnert B E, Iyer R
Bioscience Division, Los Alamos National Laboratory, New Mexico 87545, USA.
Hum Exp Toxicol. 2002 Feb;21(2):65-9. doi: 10.1191/0960327102ht212oa.
Reactive oxygen species (ROS), which contribute to the energy landscapes in and around cells, play numerous roles in maintaining normal cell homeostasis as components of signaling pathways. Excessively high levels of ROS, on the other hand, can lead to pronounced DNA damage and a variety of cellular responses, including cell cycle arrests, senescence, apoptosis and possibly cancer. Far less is known, however, about how supra-basal levels of ROS that can be generated in response to low doses of ionizing radiation or chemicals in the environment may bring about untoward or perhaps even beneficial cellular responses. Even so, some evidence suggests that adaptive responses that have been associated with ROS-generating stimuli can have protective effects by fundamentally altering subsequent cellular dose-response profiles to otherwise detrimental stresses. Yet, even these seemingly favorable 'adaptive' effects may have longer-term untoward consequences. Other effects that have been associated with supra-basal levels of ROS, such as enhanced states of cell proliferation, potentially could have a protective function. But again, such increases in cell growth, which may be accompanied by greater than normal ROS-mediated damage to DNA, as well may ultimately favour the expansion of cells with heritable mutations. Unfortunately, the state of the art of our current understanding of how elevated but still low-level increases in ROS that may be induced by environmental stimuli presently precluded incorporation of supra-basal ROS-associated mechanisms in predictive risk assessment models, both at the population level and at the level of individualized risk assessment.
活性氧（ROS）作为信号通路的组成部分，参与细胞内及周围的能量代谢，在维持细胞正常稳态中发挥着多种作用。另一方面，过高水平的ROS会导致明显的DNA损伤和多种细胞反应，包括细胞周期停滞、衰老、凋亡，甚至可能引发癌症。然而，对于低剂量电离辐射或环境中的化学物质所产生的高于基础水平的ROS如何引发不良甚至可能有益的细胞反应，我们了解得还很少。即便如此，一些证据表明，与ROS生成刺激相关的适应性反应可能通过从根本上改变后续细胞对有害应激的剂量反应曲线而产生保护作用。然而，即使是这些看似有利的“适应性”效应也可能产生长期的不良后果。与高于基础水平的ROS相关的其他效应，如细胞增殖增强状态，可能具有保护功能。但同样，这种细胞生长的增加可能伴随着高于正常水平的ROS介导的DNA损伤，最终也可能有利于具有可遗传突变的细胞的扩增。不幸的是，就目前我们对环境刺激可能诱导的ROS水平升高但仍处于低水平增加的理解而言，在人群水平和个体风险评估层面的预测风险评估模型中，都无法纳入与高于基础水平的ROS相关的机制。
