Decoding Chromosome Radiosensitivity in G0-Phase PBMCs: Genomic Determinants, Age, Sex effects, and Implications in Radiation Dose Assessment

Low-dose ionizing radiation from natural and anthropogenic sources is typically not of significant concern under normal conditions. However, in case of radiological incidents, it becomes an important environmental hazard, raising concern for public health and necessitating reliable biological indicators of exposure. Chromosomal aberrations are most reliable markers of radiation exposure and are more or less universally assessed in metaphases. Recently, rapid assessment of aberrations in G-phase lymphocytes using G-PCC-FISH has gained attention and is recognized as the most suitable method for dose assessment in cases of high-dose or partial-body exposure. This is first study in G-phase at such scale to establish baseline and radiation induced aberrations in peripheral blood mononuclear cells (PBMCs) from 24 healthy human donors (12 males, 12 females, 21-60 Y). Using whole chromosome painting (WCP) of Chromosomes 1, 2 & 4 and scoring across >8500 cells post 0, 2, and 4 Gy {gamma}-radiation exposure, we quantified 5586 aberrations and investigated their relationship with underlying genomic features. Our findings includeNo significant effect of age or sex on chromosomal radiosensitivity, supporting the robustness of pooled biodosimetric calibration curves for dose assessment within the studied age range of 21-60 years. Chromosome-specific radiosensitivity does not appear to be solely dependent on chromosome size and shows a potential association with gene density and total transcript length. From public health point of view the present data provides reference values for interphase chromosomal damage as well as radiation induced reference values for two important dose points across age groups and sexes. This approach enhances emergency preparedness for radiological events by enabling rapid biodosimetry, especially critical when metaphase cells are unavailable as in cases of accidental high-dose or partial exposures. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/728688v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@4f8a68org.highwire.dtl.DTLVardef@7ed80org.highwire.dtl.DTLVardef@7977bforg.highwire.dtl.DTLVardef@a4c0be_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO A 24-donor study to assess baseline and radiation response age and sex. Additionally substantial data analysed to assess radiosensitivity of chromosomes and its genomic determinants. C_FIG