How to explain the sensitivity of DNA double-strand breaks yield to 125I position?

Mario Enrique Alcocer ÁvilaCELIA, IP2I Lyon, Elif HindiéIUF, INCIA, Christophe ChampionCELIA
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Abstract

Purpose: Auger emitters exhibit interesting features due to their emission of a cascade of short-range Auger electrons. Maximum DNA breakage efficacy is achieved when decays occur near DNA. Studies of double-strand breaks (DSBs) yields in plasmids revealed cutoff distances from DNA axis of 10.5-12 {\AA}, beyond which the mechanism of DSBs moves from direct to indirect effects, and the yield decreases rapidly. Some authors suggested that the average energy deposited in a DNA cylinder could explain such cutoffs. We aimed to study this hypothesis in further detail.Materials and methods: Using the Monte Carlo code CELLDOSE, we investigated the influence of the 125I atom position on energy deposits and absorbed doses per decay not only in a DNA cylinder, but also in individual strands, each modeled as 10 spheres encompassing the fragility sites for phosphodiester bond cleavage.Results: The dose per decay decreased much more rapidly for a sphere in the proximal strand than for the DNA cylinder. For example, when moving the 125I source from 10.5 {\AA} to 11.5 {\AA}, the average dose to the sphere dropped by 43%, compared to only 13% in the case of the cylinder.Conclusions: Explaining variations in DSBs yields with 125I position should consider the probability of inducing damage in the proximal strand (nearest to the 125I atom). The energy received by fragility sites in this strand is highly influenced by the isotropic (4$\pi$) emission of 125I low-energy Auger electrons. The positioning of Auger emitters for targeted radionuclide therapy can be envisioned accordingly.
如何解释 DNA 双链断裂对 125I 位置的敏感性?
目的:奥奇发射器因其发射的短程奥奇电子级联而呈现出有趣的特征。当衰变发生在 DNA 附近时,DNA 的断裂效率最高。对质粒中双链断裂(DSBs)产量的研究表明,DNA轴的截止距离为10.5-12 {\AA} ,超过这个距离,DSBs的机制就会从直接效应转变为间接效应,产量也会迅速下降。一些学者认为,沉积在DNA圆柱中的平均能量可以解释这种截点。我们旨在进一步详细研究这一假设:使用蒙特卡洛代码CELLDOSE,我们不仅研究了125I原子位置对DNA圆柱体中能量沉积和每次衰变吸收剂量的影响,还研究了单条链(每条链建模为10个球体,包含磷酸二酯键裂解的脆性位点)中能量沉积和每次衰变吸收剂量的影响:结果:与 DNA 柱相比,近端链中的球体的每次衰变剂量下降得更快。例如,当 125I 源从 10.5 {\AA} 移动到 11.5 {\AA} 时,球体的平均剂量下降了 43%,而圆柱体的平均剂量仅下降了 13%:解释 125I 位置对 DSB 产量的影响时,应考虑在近端链上(离 125I 原子最近的位置)诱发损伤的概率。脆性位点在该链中接收到的能量在很大程度上受 125I 低能奥杰电子的各向同性(4$\pi$)发射的影响。可以据此设想用于放射性核素靶向治疗的奥杰电子发射器的位置。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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