Pan centromeric FISH enhances precision in radiation biodosimetry

Abstract

Abstract Accurate biodosimetry is critical for assessing radiation exposure in radiological emergencies, occupational monitoring, and clinical management, where precise dose estimation informs life-saving decisions and regulatory compliance. Current gold-standard cytogenetic methods face limitations in sensitivity and reproducibility, especially at low doses (< 0.5 Gy) (practical limitations at low doses, including very low dicentric yields, higher statistical noise, and greater scoring uncertainty as aberration frequencies near background levels). This study presents a systematic comparison of pan-centromeric fluorescence in situ hybridization (pan-cent-FISH) and Giemsa staining for detecting dicentric (DC) and ring (R) chromosomes following 60 Co-γ irradiation (0–3 Gy). Analysis of more than 15,000 metaphases per technique revealed enhanced sensitivity of pan-cent-FISH technique, demonstrating a 1.72-fold higher linear coefficient and enhanced (1.13-fold) quadratic coefficient (β), indicating improved sensitivity across both low and high dose ranges. Blind validation with eight samples showed pan-cent-FISH achieved ~ 2-fold greater accuracy, with mean absolute differences of 0.0538 Gy (vs. 0.1105 Gy for Giemsa) and average relative errors of 7.13% (vs. 15.35% for Giemsa). At low doses (0.1 Gy), pan-cent-FISH maintained 9.0% error, while Giemsa exceeded acceptable limits (21.0% error). The standardized fluorescence detection used for the technique eliminated morphological ambiguities, reducing false negatives by ~ 40% and improving first-pass accuracy.