Center for Radiological Research, Columbia University Medical Center, 630 West 168th St., New York, NY 10032, USA.
J Theor Biol. 2009 Nov 21;261(2):305-17. doi: 10.1016/j.jtbi.2009.08.003. Epub 2009 Aug 11.
Ionizing radiation triggers oxidative stress, which can have a variety of subtle and profound biological effects. Here we focus on mathematical modeling of potential synergistic interactions between radiation damage to DNA and oxidative stress-induced damage to proteins involved in DNA repair/replication. When sensitive sites on these proteins are attacked by radiation-induced radicals, correct repair of dangerous DNA lesions such as double strand breaks (DSBs) can be compromised. In contrast, if oxidation of important proteins is prevented by strong antioxidant defenses, DNA repair may function more efficiently. These processes probably occur to some extent even at low doses of radiation/oxidative stress, but they are easiest to investigate at high doses, where both DNA and protein damage are extensive. As an example, we use data on survival of Deinococcus radiodurans after high doses (thousands of Gy) of acute and chronic irradiation. Our model of radiogenic oxidative stress is consistent with these data and can potentially be generalized to other organisms and lower radiation doses.
电离辐射会引发氧化应激，从而产生各种微妙而深远的生物学效应。在这里，我们专注于数学建模，研究辐射对 DNA 的损伤与氧化应激诱导的 DNA 修复/复制相关蛋白损伤之间可能存在的协同作用。当这些蛋白上的敏感位点受到辐射诱导自由基的攻击时，对双链断裂（DSB）等危险 DNA 损伤的正确修复可能会受到影响。相比之下，如果通过强大的抗氧化防御来防止重要蛋白的氧化，则 DNA 修复可能会更有效地发挥作用。即使在低剂量的辐射/氧化应激下，这些过程也可能在一定程度上发生，但在高剂量下，DNA 和蛋白质损伤广泛存在，这些过程最容易被研究。作为一个例子，我们使用了 Deinococcus radiodurans 在高剂量（数千戈瑞）急性和慢性照射后的存活数据。我们的放射氧化性应激模型与这些数据一致，并有可能推广到其他生物体和更低的辐射剂量。
