A model of interactions between radiation-induced oxidative stress, protein and DNA damage in Deinococcus radiodurans

被引:27
|
作者
Shuryak, Igor [1 ]
Brenner, David J. [1 ]
机构
[1] Columbia Univ, Med Ctr, Ctr Radiol Res, New York, NY 10032 USA
基金
美国国家卫生研究院;
关键词
Mathematical model; DNA repair; Protein oxidation; Dose response; Clonogenic survival; Bacteria; Deinococcus radiodurans; STRAND BREAK REPAIR; HYDROGEN-PEROXIDE ELIMINATION; FREE-RADICAL REACTIONS; IONIZING-RADIATION; SHEWANELLA-ONEIDENSIS; INACTIVATION; CELLS; RESISTANCE; SURVIVAL; REDOX;
D O I
10.1016/j.jtbi.2009.08.003
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:305 / 317
页数:13
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