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染色质环导致高传能线密度辐射诱导产生的小DNA片段数量增加,而染色体结构域并不影响片段大小。

Chromatin loops are responsible for higher counts of small DNA fragments induced by high-LET radiation, while chromosomal domains do not affect the fragment sizes.

作者信息

Ponomarev Artem L, Cucinotta Francis A

机构信息

USRA, Houston, Texas, USA.

出版信息

Int J Radiat Biol. 2006 Apr;82(4):293-305. doi: 10.1080/09553000600637716.

Abstract

PURPOSE

To apply a polymer model of DNA damage induced by high-LET (linear energy transfer) radiation and determine the influence of chromosomal domains and loops on fragment length distribution.

MATERIALS AND METHODS

The yields of DSB (double-strand breaks) induced by high-LET radiation were calculated using a track structure model along with a polymer model of DNA packed in the cell nucleus. The cell nucleus was constructed to include the chromosomal domains and chromatin loops. The latter were generated by the random walk method.

RESULTS AND CONCLUSIONS

We present data for DSB yields per track per cell, DNA fragment sizes, the radial distribution of DSB with respect to the track center, and the distribution of 0, 1, 2, and more DSB from a single particle. Calculations were carried out for a range of particles including He (40 keV/microm), N (225 keV/microm), and Fe ions (150 keV/mum). Situations relevant to PFGE (pulsed-field gel electrophoresis) and microbeam experiments with direct irradiation of the cell nucleus were simulated to demonstrate the applicability of the model. Data show that chromosomal domains do not have a significant influence on fragment-size distribution, while the presence of DNA loops increases the frequencies of smaller fragments by nearly 30% for fragment sizes in the range from 2 kbp (bp = base pair) to 20 kbp.

摘要

目的

应用高传能线密度(LET)辐射诱导的DNA损伤聚合物模型,确定染色体结构域和环对片段长度分布的影响。

材料与方法

使用径迹结构模型以及细胞核中包装的DNA聚合物模型,计算高LET辐射诱导的双链断裂(DSB)产额。构建的细胞核包含染色体结构域和染色质环。染色质环通过随机游走方法生成。

结果与结论

我们给出了每个细胞每条径迹的DSB产额、DNA片段大小、DSB相对于径迹中心的径向分布以及单个粒子产生的0、1、2及更多个DSB的分布数据。对一系列粒子进行了计算,包括氦离子(40 keV/μm)、氮离子(225 keV/μm)和铁离子(150 keV/μm)。模拟了与脉冲场凝胶电泳(PFGE)和直接照射细胞核的微束实验相关的情况,以证明该模型的适用性。数据表明,染色体结构域对片段大小分布没有显著影响,而对于2 kbp(bp = 碱基对)至20 kbp范围内的片段大小,DNA环的存在使较小片段的频率增加了近30%。

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