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

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 ¹²⁵I at 0.006 ± 0.003 DSBs·cell⁻¹·mGy⁻¹, while ^99mTc 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 (⁶³Ni) and 1.06 ± 0.15 mGy∙h⁻¹∙MBq⁻¹ (¹²⁵I) to 61.83 ± 1.17 mGy∙h⁻¹∙MBq⁻¹ (⁹⁰Sr). For alpha-emitting radionuclides, ²¹³Bi produced 0.0677 ± 0.0005 DSB·cell⁻¹·mGy⁻¹ while ²³²Th 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 ²⁵²Cf to 16.8 ± 0.1 DSBs/µm for ²³²Th. The S-values for lymphocyte nuclei for alpha emitters varied, from ²³²Th (0.29 ± 0.21 Gy∙h⁻¹∙MBq⁻¹) to ²²⁷Th 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.