Clinical and translational radiation oncology · 2025
Continuous β- particle exposure: A study of DNA damage in ex vivo peripheral blood mononuclear cells irradiation with Radioiodine.
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Mazzitelli-Fuentes Laura, Negrin Lara, Venier Virginia, Romano Humberto, Pereira Lucia, Leberle Jerónimo, Ausas Maria Soledad, Choudhury Ananya, Biolatti Luisa V
Аннотация
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.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.
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.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.