DNA damage induced by radiation of different linear energy transfer:: initial fragmentation

DNA damage induced by radiation of different linear energy transfer:: initial fragmentation
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DOI:
10.1080/095530000138556
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发表时间:
2000-04-01
影响因子:
2.6
通讯作者:
Stenerlöw, B
Stenerlöw, B
中科院分区:
医学3区
文献类型:
--
作者:
Höglund, E;Blomquist, E;Stenerlöw, B

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目的:研究40-225keV/mLET加速离子辐照后DNA断裂与线性能量转移(LET)的关系。材料与方法:用Co-60光子、氦离子照射低传代人成纤维细胞GM 5758后,分析5kBBP~5.7MBP范围内双链DNA的断裂模式。采用两种不同的脉冲场凝胶电泳法,分别用于分离1-6MBP和5KBP-1.5MBP的片段。结果:高LET照射后,DNA短小和中等大小片段的形成几率增加。Co-60光子和离子的DNA双链断裂(DSB)诱导率分别为5.8和6.9-8.8×10(-9)DSB BP(-1)Gy1。在不考虑碎片分布的情况下,离子产率比按常规方法计算的离子产率高出约80110%。对于光子,产量要高出13%。相应的相对生物学效应(RBE)在1.2~1.5之间。结论:脉冲场凝胶电泳法对高LET照射后DSB的数量有显著的非随机性贡献。LET对初始DNA片段的分布有很大的影响,因此也对所测得的诱导率有很大影响。然而,当LET增加到研究的氮离子的最高值时,产率略有下降。
Purpose: To investigate DNA fragmentation as a function of linear energy transfer (LET) after exposure to accelerated ions in the LET range 40-225 keV/mu m.Materials and methods: Fragmentation patterns of double-stranded DNA in the range 5 kilobasepairs (kbp) to 5.7 megabasepairs (Mbp) were analysed after irradiation of low-passage GM 5758 normal human fibroblast cells with Co-60-photons, helium ions at. 40 keV/mu m and high-LET nitrogen ions between 80 and 225 keV/mu m. Two separate pulsed-field gel electrophoresis protocols were used, optimized for separation of 1-6 Mbp and 5 kbp to 1.5 Mbp, fragments.Results: An increased probability of formation of short and medium-sized DNA fragments was revealed following high-LET irradiation. The DNA double-strand break (dsb) induction yields were, respectively, 5.8 and 6.9-8.8 x 10(-9) dsb bp(-1) Gy(-1) for Co-60-photons and ions. The ion yields were some 80 110% higher than those calculated according to a conventional approach, disregarding the fragment distributions. For photons, the yield was 13% higher. The corresponding relative biological effectiveness (RBE) of dsb induction was in the range 1.2-1.5.Conclusions: A significant non-random contribution to the number of dsb after irradiation with high-LET was confirmed by detailed fragment analysis using pulsed-field gel electrophoresis. The LET had a strong influence on the initial DNA fragment distribution, and hence also on the induction yields measured. However, when the LET was increased to the highest values studied for nitrogen ions, the yield decreased slightly.