Factors Influencing Double-Strand Break Focus Biodosimetry for Detection of Internal Low-LET Irradiation in Human...

Radiological or nuclear incidents can release radionuclide mixtures that contaminate populations in fallout areas. Medical management may involve biodosimetry assays to identify individuals who need care. The γ-H2AX + 53BP1 double-strand break (DSB) focus assay is a rapid triage tool for detecting irradiated individuals, but its specificity is limited by physiological background foci and individual variability. In this study, we characterized baseline γ-H2AX + 53BP1 DSB foci levels in peripheral blood mononuclear cells from 60 healthy volunteers (31 men, 29 women), aged 20-64 years, to assess the influence of age and sex. The detection threshold was set at the 95th percentile of baseline foci values. This threshold was tested against data based on blood samples from 10 donors irradiated ex vivo with [223Ra]RaCl2 and [177Lu]LuCl3 mixtures at absorbed doses to the blood of 25-75 mGy (β-contribution only), measured at 0, 4, and 24 h postirradiation. The median baseline foci value was 0.51 foci/cell (IQR: 0.41-0.63). Older individuals showed significantly higher baseline levels (P = 0.03), with greater variability, while no sex differences were observed. Setting the threshold at 0.86 foci/cell enabled reliable detection of irradiated samples shortly after exposure (sensitivity: 96.7%; specificity: 95.0%). However, sensitivity decreased at 4 h (63.3%) and 24 h (36.7%) postirradiation due to DNA repair. These findings suggest that individuals irradiated with low doses can be identified soon after exposure using the DSB focus assay. Age-related variability and DNA repair kinetics should be considered in emergency biodosimetry planning.