Laura Mazzitelli-Fuentes , Lara Negrin , Virginia Venier , Humberto Romano , Lucia Pereira , Jerónimo Leberle , Maria Soledad Ausas , Ananya Choudhury , Luisa V. Biolatti
{"title":"连续β -颗粒暴露:放射性碘辐照对体外外周血单个核细胞DNA损伤的研究","authors":"Laura Mazzitelli-Fuentes , Lara Negrin , Virginia Venier , Humberto Romano , Lucia Pereira , Jerónimo Leberle , Maria Soledad Ausas , Ananya Choudhury , Luisa V. Biolatti","doi":"10.1016/j.ctro.2025.101040","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and purpose</h3><div>Targeted radionuclide therapy (TRT) is a promising cancer treatment, but insufficient knowledge of the biological dose–response relationships limits its efficacy. The aim of this study was to characterize DNA damage in peripheral blood mononuclear cells (PBMCs) exposed to β-continuous irradiation (<sup>131</sup>I), and to assess its relationship with the absorbed dose, using two biomarkers: dicentric chromosomes and γ-H2AX foci.</div></div><div><h3>Materials and methods</h3><div>PBMCs from healthy donors were exposed to <sup>131</sup>I at various activities (0.37–3.7 MBq) and times (1, 4, 24 h). Absorbed doses were calculated using the Medical Internal Radiation Dose formalism. DNA damage was assessed by chromosomal aberration frequency and γ-H2AX foci quantification. Lithium chloride (LiCl) was used to evaluate the rescue of delayed foci formation after 24 h exposure.</div></div><div><h3>Results</h3><div>Continuous β-irradiation induced a linear increase in CAs (α = 0.0643 ± 0.0068), in contrast to the linear-quadratic response observed in acute X-ray exposure (α = 0.0359 ± 0.0093, β = 0.0673 ± 0.0042). The frequency of CAs is lower under radionuclide irradiation compared to X-rays. γ-H2AX increased significantly at 1 and 4 h of continuous exposure but diminished at 24 h, despite continuous irradiation. LiCl treatment partially restored γ-H2AX foci levels at 24 h.</div></div><div><h3>Conclusion</h3><div>Dose-response relationship under continuous β-irradiation, assessed by CAs, follows a linear trend. DNA damage induced foci show a time-dependent dynamic. The decline in foci at 24 h, reversible with LiCl, highlights the limitations of γ-H2AX as a biomarker under prolonged irradiation conditions. These findings emphasize the need for optimized dosimetry methods and identify reliable biomarkers in TRT.</div><div>Abbreviations: TRT, targeted radionuclide therapy; MIRD, Medical Internal Radiation Dose; EBRT, external beam radiotherapy; LQ, linear-quadratic; DCA, dicentric chromosome assay; DSB, double strand break; PBMCs, peripheral blood mononuclear cells; PB, peripheral blood; FBS, fetal bovine serum; PBS, phosphate-buffered saline; CAs, chromosomal aberrations; RT, room temperature.</div></div>","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"55 ","pages":"Article 101040"},"PeriodicalIF":2.7000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Continuous β− particle exposure: A study of DNA damage in ex vivo peripheral blood mononuclear cells irradiation with Radioiodine\",\"authors\":\"Laura Mazzitelli-Fuentes , Lara Negrin , Virginia Venier , Humberto Romano , Lucia Pereira , Jerónimo Leberle , Maria Soledad Ausas , Ananya Choudhury , Luisa V. Biolatti\",\"doi\":\"10.1016/j.ctro.2025.101040\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and purpose</h3><div>Targeted radionuclide therapy (TRT) is a promising cancer treatment, but insufficient knowledge of the biological dose–response relationships limits its efficacy. The aim of this study was to characterize DNA damage in peripheral blood mononuclear cells (PBMCs) exposed to β-continuous irradiation (<sup>131</sup>I), and to assess its relationship with the absorbed dose, using two biomarkers: dicentric chromosomes and γ-H2AX foci.</div></div><div><h3>Materials and methods</h3><div>PBMCs from healthy donors were exposed to <sup>131</sup>I at various activities (0.37–3.7 MBq) and times (1, 4, 24 h). Absorbed doses were calculated using the Medical Internal Radiation Dose formalism. DNA damage was assessed by chromosomal aberration frequency and γ-H2AX foci quantification. Lithium chloride (LiCl) was used to evaluate the rescue of delayed foci formation after 24 h exposure.</div></div><div><h3>Results</h3><div>Continuous β-irradiation induced a linear increase in CAs (α = 0.0643 ± 0.0068), in contrast to the linear-quadratic response observed in acute X-ray exposure (α = 0.0359 ± 0.0093, β = 0.0673 ± 0.0042). The frequency of CAs is lower under radionuclide irradiation compared to X-rays. γ-H2AX increased significantly at 1 and 4 h of continuous exposure but diminished at 24 h, despite continuous irradiation. LiCl treatment partially restored γ-H2AX foci levels at 24 h.</div></div><div><h3>Conclusion</h3><div>Dose-response relationship under continuous β-irradiation, assessed by CAs, follows a linear trend. DNA damage induced foci show a time-dependent dynamic. The decline in foci at 24 h, reversible with LiCl, highlights the limitations of γ-H2AX as a biomarker under prolonged irradiation conditions. These findings emphasize the need for optimized dosimetry methods and identify reliable biomarkers in TRT.</div><div>Abbreviations: TRT, targeted radionuclide therapy; MIRD, Medical Internal Radiation Dose; EBRT, external beam radiotherapy; LQ, linear-quadratic; DCA, dicentric chromosome assay; DSB, double strand break; PBMCs, peripheral blood mononuclear cells; PB, peripheral blood; FBS, fetal bovine serum; PBS, phosphate-buffered saline; CAs, chromosomal aberrations; RT, room temperature.</div></div>\",\"PeriodicalId\":10342,\"journal\":{\"name\":\"Clinical and Translational Radiation Oncology\",\"volume\":\"55 \",\"pages\":\"Article 101040\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Translational Radiation Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2405630825001326\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Radiation Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2405630825001326","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Continuous β− particle exposure: A study of DNA damage in ex vivo peripheral blood mononuclear cells irradiation with Radioiodine
Background and purpose
Targeted radionuclide therapy (TRT) is a promising cancer treatment, but insufficient knowledge of the biological dose–response relationships limits its efficacy. The aim of this study was to characterize DNA damage in peripheral blood mononuclear cells (PBMCs) exposed to β-continuous irradiation (131I), and to assess its relationship with the absorbed dose, using two biomarkers: dicentric chromosomes and γ-H2AX foci.
Materials and methods
PBMCs from healthy donors were exposed to 131I at various activities (0.37–3.7 MBq) and times (1, 4, 24 h). Absorbed doses were calculated using the Medical Internal Radiation Dose formalism. DNA damage was assessed by chromosomal aberration frequency and γ-H2AX foci quantification. Lithium chloride (LiCl) was used to evaluate the rescue of delayed foci formation after 24 h exposure.
Results
Continuous β-irradiation induced a linear increase in CAs (α = 0.0643 ± 0.0068), in contrast to the linear-quadratic response observed in acute X-ray exposure (α = 0.0359 ± 0.0093, β = 0.0673 ± 0.0042). The frequency of CAs is lower under radionuclide irradiation compared to X-rays. γ-H2AX increased significantly at 1 and 4 h of continuous exposure but diminished at 24 h, despite continuous irradiation. LiCl treatment partially restored γ-H2AX foci levels at 24 h.
Conclusion
Dose-response relationship under continuous β-irradiation, assessed by CAs, follows a linear trend. DNA damage induced foci show a time-dependent dynamic. The decline in foci at 24 h, reversible with LiCl, highlights the limitations of γ-H2AX as a biomarker under prolonged irradiation conditions. These findings emphasize the need for optimized dosimetry methods and identify reliable biomarkers in TRT.