Spectrum of complex DNA damages depends on the incident radiation

Spectrum of complex DNA damages depends on the incident radiation
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DOI:
10.1667/rr3498.1
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发表时间:
2006-02-01
期刊:
影响因子:
3.4
通讯作者:
Sutherland, BM
Sutherland, BM
中科院分区:
医学3区
文献类型:
--
作者:
Hada, M;Sutherland, BM

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电离辐射会诱发双链聚集性损伤——两个或多个脱碱基位点、氧化碱基以及几个螺旋圈内相对 DNA 链上的链断裂。由于簇难以修复并且是双链断裂 (DSB) 的潜在来源,因此它们具有潜在的致命性和致突变性。尽管单链断裂(SSB)和孤立损伤的诱导已被广泛研究,但除了 DSB 之外,对影响簇诱导的因素知之甚少。为了确定入射辐射的类型是否会影响特定簇的产量或光谱,我们用离子束[铁(970 MeV/核子)、碳(293 MeV/核子)、钛(980 MeV/核子)、硅(586 MeV/核子)、质子(1 GeV/核子)]照射基因组T7 DNA(一种简单的40 kbp线性平端分子)或 100 kVp X 射线,然后使用凝胶电泳、电子成像和数均长度分析对 DSB、Fpg-oxypurine 簇和 Nfo-basic 簇进行定量。所有损伤的产量(损伤/Mbp Gy(-1))随着辐射线性能量转移(LET)的增加而降低。与无碱基和氧碱基团簇相比,带电粒子(包括高能、低 LET 质子)的 DSB 相对频率高于电离光子。 (c) 2006 年,辐射研究协会。
Ionizing radiation induces bistranded clustered damages-two or more abasic sites, oxidized bases and strand breaks on opposite DNA strands within a few helical turns. Since clusters are refractory to repair and are potential sources of double-strand breaks (DSBs), they are potentially lethal and mutagenic. Although induction of single-strand breaks (SSBs) and isolated lesions has been studied extensively, little is known about the factors affecting induction of clusters other than DSBs. To determine whether the type of incident radiation could affect the yields or spectra of specific clusters, we irradiated genomic T7 DNA, a simple 40-kbp linear, blunt-ended molecule, with ion beams [iron (970 MeV/nucleon), carbon (293 MeV/nucleon), titanium (980 MeV/nucleon), silicon (586 MeV/nucleon), protons (1 GeV/nucleon)] or 100 kVp X rays and then quantified DSBs, Fpg-oxypurine clusters and Nfo-abasic clusters using gel electrophoresis, electronic imaging and number average length analysis. The yields (damages/Mbp Gy(-1)) of all damages decreased with increasing linear energy transfer (LET) of the radiation. The relative frequencies of DSBs compared to abasic and oxybase clusters were higher for the charged particles-including the high-energy, low-LET protons-than for the ionizing photons. (c) 2006 by Radiation Research Society.