Urinary 8‑OHdG and MDA as rapid biodosimetry markers in the lethal/sublethal dose range

Rapid and accurate assessment of ionizing radiation exposure is essential for effective triage in acute radiation syndrome. However, although several biodosimetry approaches are available (such as clinical signs, routine laboratory markers and cytogenetic assays), rapid and scalable dose stratification remains challenging in large‑scale emergencies. The present study evaluated two oxidative stress‑related urinary metabolites, 8‑hydroxy‑2'‑deoxyguanosine (8‑OHdG) and malondialdehyde (MDA), as candidate biomarkers in the high‑dose exposure range. Male C57BL/6NJcl mice (8 weeks) received whole‑body X‑irradiation (0‑10 Gy at 1.0 Gy/min). Urine samples were collected at 24 or 72 h postexposure. Urinary 8‑OHdG was quantified using a lateral flow immunochromatographic assay (with ELISA validation) and MDA levels were measured using a thiobarbituric acid‑reactive substances assay. Values were normalized to creatinine. Tissue distribution was assessed across multiple organs, and bone marrow cell cultures were used to examine extracellular release and to support tissue‑origin inference under controlled conditions. Bone marrow injury was evaluated by flow cytometry detection of apoptotic cells. Urinary 8‑OHdG and MDA levels increased dose‑dependently, with significant correlations (8‑OHdG: r=0.55 at 24 h, r=0.50 at 72 h; MDA: r=0.65 at 24 h, r=0.50 at 72 h; all P<0.05). A sharp rise occurred at ≥7 Gy, where 8‑OHdG levels rose 3.7‑fold and MDA levels rose 2.3‑fold relative to controls. Tissue analyses identified the bone marrow and spleen as primary sources. In vitro bone marrow cultures confirmed dose‑dependent release, while cell death profiling indicated a shift toward necrosis at high doses. Together, these findings supported the potential utility of urinary 8‑OHdG and MDA as rapid and noninvasive biomarkers for early risk stratification in radiation emergencies.