A significant role of non-thermal equilibrated electrons in the formation of deleterious complex DNA damage
A significant role of non-thermal equilibrated electrons in the formation of deleterious complex DNA damage
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DOI：
10.1039/c7cp06903k
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发表时间：
2018-01-28
影响因子：
3.3
通讯作者：
Watanabe, Ritsuko
中科院分区：
文献类型：
--
作者：
Kai, Takeshi;Yokoya, Akinari;Watanabe, Ritsuko
尽管使用活细胞中的修复酶可以使基因组DNA的大部分辐射损伤变得无害，但一定比例的损伤是持续的，从而导致严重的遗传效应，如突变诱导。为了从辐射径迹末端最早的物理阶段来理解有害DNA损伤形成的机制，用动态蒙特卡罗程序研究了DNA分子周围低能电子的动力学及其热化过程。一次入射电子(1keV)在1 nm内倍增碰撞(相当于3个DNA碱基对，3BP)，并在300fs内产生非高斯和非热平衡分布的二次电子。另一方面，次级电子主要分布在离母阳离子约10 nm的范围内，但由于库仑场的相互作用，约有5%的电子定域在离阳离子1 nm的范围内。平均电子能量为0.7 eV；然而，在300fs时，超过10%的电子落入比0.1 eV低得多的能区。这些结果表明，预水化电子是由离阳离子几纳米的极减速电子形成的。因此，包括多个碱基损伤或单链断裂的DNA损伤部位可以由这些电子在3bp内的多次碰撞形成。这种多重损伤部位很难被碱基切除修复酶处理。然而，也可以产生预水化电子，导致距离多损伤部位超过3BP的额外碱基损伤(或链断裂)。当碱基切除酶处理额外的碱基损伤时，这些损伤位置可能最终转化为双链断裂(DSB)。这种双链断裂在其末端包括另一个碱基损伤(S)，并可能通过双链断裂修复酶引入错配重新连接，从而可能导致存活细胞的突变等生物学效应。
Although most of the radiation damage to genomic DNA could be rendered harmless using repair enzymes in a living cell, a certain fraction of the damage is persistent resulting in serious genetic effects, such as mutation induction. In order to understand the mechanisms of the deleterious DNA damage formation in terms of its earliest physical stage at the radiation track end, dynamics of low energy electrons and their thermalization processes around DNA molecules were investigated using a dynamic Monte Carlo code. The primary incident (1 keV) electrons multiply collide within 1 nm (equivalent to three DNA-base-pairs, 3bp) and generate secondary electrons which show non-Gaussian and non-thermal equilibrium distributions within 300 fs. On the other hand, the secondary electrons are mainly distributed within approximately 10 nm from their parent cations although approximately 5% of the electrons are localized within 1 nm of the cations owing to the interaction of their Coulombic fields. The mean electron energy is 0.7 eV; however, more than 10% of the electrons fall into a much lower-energy region than 0.1 eV at 300 fs. These results indicate that pre-hydrated electrons are formed from the extremely decelerated electrons over a few nm from the cations. DNA damage sites comprising multiple nucleobase lesions or single strand breaks can therefore be formed by multiple collisions of these electrons within 3bp. This multiple damage site is hardly processed by base excision repair enzymes. However, pre-hydrated electrons can also be produced resulting in an additional base lesion (or a strand break) more than 3bp away from the multi-damage site. These damage sites may be finally converted into a double strand break (DSB) when base excision enzymes process the additional base lesions. This DSB includes another base lesion(s) at their termini, and may introduce miss-rejoining by DSB repair enzymes, and hence may result in biological effects such as mutation in surviving cells.