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

IF 2.1 4区 医学 Q2 BIOLOGY International Journal of Radiation Biology Pub Date : 2023-01-01 DOI:10.1080/09553002.2022.2047822
Mario Enrique Alcocer Ávila, Elif Hindié, Christophe Champion
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引用次数: 2

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 Å-12 Å, 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 Å to 11.5 Å, 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 (4π) emission of 125I low-energy Auger electrons. The positioning of Auger emitters for targeted radionuclide therapy can be envisioned accordingly.

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如何解释DNA双链断裂率对125I位置的敏感性?
目的:俄歇发射体表现出有趣的特征,因为它们发射的是一串短程俄歇电子。当DNA附近发生衰变时,达到最大的DNA断裂效果。对质粒中双链断裂(DSBs)产率的研究表明,与DNA轴的切断距离为10.5 Å-12 Å,超过这个距离,DSBs的作用机制从直接作用转向间接作用,产率迅速下降。一些作者认为,储存在DNA圆柱体中的平均能量可以解释这种切断。我们的目的是进一步详细研究这一假设。材料和方法:使用蒙特卡罗代码CELLDOSE,我们研究了125I原子位置对能量沉积和每次衰变的吸收剂量的影响,不仅在DNA圆柱体中,而且在单个链中,每个链被建模为包含磷酸二酯键断裂的脆弱位点的10个球体。结果:在近端链中,每次衰减的剂量比在DNA圆柱体中下降得快得多。例如,当125I源从10.5 Å移动到11.5 Å时,球体的平均剂量下降了43%,而在圆柱体的情况下仅下降了13%。结论:解释dsb产率随125I位置的变化应考虑近端链(最靠近125I原子)诱导损伤的可能性。该链中脆弱位点所接收的能量受到125I低能俄歇电子的各向同性(4π)发射的高度影响。可以相应地设想用于靶向放射性核素治疗的俄歇发射器的定位。
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来源期刊
CiteScore
5.00
自引率
11.50%
发文量
142
审稿时长
3 months
期刊介绍: The International Journal of Radiation Biology publishes original papers, reviews, current topic articles, technical notes/reports, and meeting reports on the effects of ionizing, UV and visible radiation, accelerated particles, electromagnetic fields, ultrasound, heat and related modalities. The focus is on the biological effects of such radiations: from radiation chemistry to the spectrum of responses of living organisms and underlying mechanisms, including genetic abnormalities, repair phenomena, cell death, dose modifying agents and tissue responses. Application of basic studies to medical uses of radiation extends the coverage to practical problems such as physical and chemical adjuvants which improve the effectiveness of radiation in cancer therapy. Assessment of the hazards of low doses of radiation is also considered.
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