通过对淋巴细胞进行45种发射α和β/γ射线的放射性核素的体内外照射，对辐射诱导的双链断裂进行计算机模拟分析。

In silico analysis of radiation-induced double-strand breaks by internal ex vivo irradiation of lymphocytes for 45 alpha- and beta/gamma-emitting radionuclides.

作者信息

Salas-Ramirez Maikol, Lassmann Michael, Eberlein Uta

机构信息

Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.

出版信息

EJNMMI Res. 2025 Mar 10;15(1):21. doi: 10.1186/s13550-025-01214-w.

DOI:10.1186/s13550-025-01214-w

PMID:40063302

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11893945/

Abstract

BACKGROUND

The aim of this study is to evaluate the induction of DNA damage by 45 radionuclides, including those used in medical applications and others relevant to radiation protection. The research focuses on understanding the differential effects of irradiating lymphocytes with beta/gamma- and alpha-emitting radionuclides using Monte Carlo simulations. A validated Monte Carlo simulation model was used to assess radiation-induced DNA damage in lymphocytes. The model integrates GATE for macroscopic radiation transport and Geant4-DNA for microscopic simulations at the cellular level. For the study, 45 radionuclides were selected and their S-values and DNA double-strand break (DSB) induction were investigated. For beta- and gamma-emitting radionuclides, DSBs per cell per mGy were quantified, while for alpha-emitters, alpha tracks per cell per mGy, DSBs per cell per mGy, and DSBs per micrometer of alpha track were calculated.

RESULT

For beta/gamma emitters, the lowest number of DSBs was observed with I at 0.006 ± 0.003 DSBs·cell⁻¹·mGy⁻¹, while Tc had the highest at approximately 0.015 ± 0.005 DSBs·cell⁻¹·mGy⁻¹. The S-value for lymphocyte nuclei ranked from 0.91 ± 0.14 mGy∙h⁻¹∙MBq⁻¹ (Ni) and 1.06 ± 0.15 mGy∙h⁻¹∙MBq⁻¹ (I) to 61.83 ± 1.17 mGy∙h⁻¹∙MBq⁻¹ (Sr). For alpha-emitting radionuclides, Bi produced 0.0677 ± 0.0005 DSB·cell⁻¹·mGy⁻¹ while Th yielded 0.0914 ± 0.0004 DSB·cell⁻¹·mGy⁻¹. The DSB linear density for alpha tracks ranged from 7.4 ± 0.1 DSBs/µm for Cf to 16.8 ± 0.1 DSBs/µm for Th. The S-values for lymphocyte nuclei for alpha emitters varied, from Th (0.29 ± 0.21 Gy∙h⁻¹∙MBq⁻¹) to Th having the highest at 2.22 ± 0.16 Gy∙h⁻¹∙MBq⁻¹, due to cumulative energy deposition.

CONCLUSIONS

Differences were observed in DNA damage induced by beta/gamma- and alpha-emitting radionuclides. High-energy beta emitters induced DSBs similarly to gamma emitters, but with greater fluctuations in low-energy beta and gamma emitters due to heterogeneous energy deposition and varying interaction probabilities at the cellular level. This study highlights that long half-life alpha-emitting radionuclides may cause more extensive DNA damage due to their higher LET. This work provides a comprehensive S-values database for future experimental studies on radiation-induced DNA damage in lymphocytes.

摘要

背景

本研究的目的是评估45种放射性核素所致的DNA损伤，包括那些用于医学应用的以及与辐射防护相关的其他放射性核素。该研究聚焦于通过蒙特卡罗模拟来理解用发射β/γ射线和发射α射线的放射性核素照射淋巴细胞的不同效应。一个经过验证的蒙特卡罗模拟模型被用于评估淋巴细胞中辐射诱导的DNA损伤。该模型整合了用于宏观辐射传输的GATE和用于细胞水平微观模拟的Geant4-DNA。在本研究中，选择了45种放射性核素，并研究了它们的S值和DNA双链断裂（DSB）诱导情况。对于发射β射线和γ射线的放射性核素，对每毫戈瑞每细胞的DSB进行了量化，而对于发射α射线的核素，计算了每毫戈瑞每细胞的α径迹数、每毫戈瑞每细胞的DSB数以及每微米α径迹的DSB数。

结果

对于发射β/γ射线的核素，观察到碘的DSB数最低，为0.006±0.003 DSB·细胞⁻¹·毫戈瑞⁻¹，而锝的DSB数最高，约为0.015±0.005 DSB·细胞⁻¹·毫戈瑞⁻¹。淋巴细胞核的S值范围从0.91±0.14毫戈瑞∙小时⁻¹∙兆贝可⁻¹（镍）和1.06±0.15毫戈瑞∙小时⁻¹∙兆贝可⁻¹（碘）到61.83±1.17毫戈瑞∙小时⁻¹∙兆贝可⁻¹（锶）。对于发射α射线的放射性核素，铋产生0.0677±0.0005 DSB·细胞⁻¹·毫戈瑞⁻¹，而钍产生0.0914±0.0004 DSB·细胞⁻¹·毫戈瑞⁻¹。α径迹的DSB线密度范围从锎的7.4±0.1 DSB/微米到钍的16.8±0.1 DSB/微米。由于累积能量沉积，发射α射线的核素的淋巴细胞核S值各不相同，从钍的0.29±0.21戈瑞∙小时⁻¹∙兆贝可⁻¹到钍的最高值2.22±0.16戈瑞∙小时⁻¹∙兆贝可⁻¹。

结论

观察到发射β/γ射线和发射α射线的放射性核素所致的DNA损伤存在差异。高能β发射体诱导的DSB与γ发射体类似，但由于细胞水平上能量沉积的不均匀性和相互作用概率的不同，低能β和γ发射体的波动更大。本研究强调，长半衰期的发射α射线的放射性核素因其较高的传能线密度可能导致更广泛的DNA损伤。这项工作为未来关于淋巴细胞中辐射诱导DNA损伤的实验研究提供了一个全面的S值数据库。