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Article

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

  • Authors:
    • Satoru Monzen
    • Kenji Terada
    • Yusuke Tawata
    • Takanori Sato
    • Nozomi Kousaka
    • Yasushi Mariya
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan, Center for Cancer Treatment and Examination, Aomori Rosai Hospital, Hachinohe, Aomori 031‑8551, Japan
  • Article Number: 174
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    Published online on: April 22, 2026
       https://doi.org/10.3892/mmr.2026.13884
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Abstract

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.
View Figures

Figure 1

Experimental workflow of the mouse
model exposed to lethal and sublethal doses of ionizing radiation
(0–10 Gy at 1.0 Gy/min). Urine and organs (liver, kidney, lung,
intestine, spleen, muscle and bone marrow) were collected at 24–72
h postexposure. Urinary 8-OHdG and MDA levels were quantified, and
cellular damage analyses were performed. 8-OHdG,
8-hydroxy-2′-deoxyguanosine; IR, ionizing radiation; MDA,
malondialdehyde.

Figure 2

Dose-response profiles of urinary
8-OHdG and MDA. Urine was collected 24 or 72 h after X-irradiation.
Urinary 8-OHdG at (A) 24 and (B) 72 h, and urinary MDA at (C) 24
and (D) 72 h. Data were fitted using regression analysis (linear or
quadratic as appropriate). Pearson r and Spearman ρ values (with
corresponding P-values) are indicated in each panel. Dashed lines
denote 95% confidence intervals. Solid lines represent the selected
best-fit model based on R2 and residual patterns, with
preference for the simpler model unless a clear improvement in fit
was observed. The reported R2 values correspond to the
selected regression model. 8-OHdG, 8-hydroxy-2′-deoxyguanosine;
MDA, malondialdehyde; NS, not significant.

Figure 3

Three-dimensional relationships among
radiation dose, urinary 8-OHdG and MDA at (A) 24 and (B) 72 h
post-irradiation. Sphere size is proportional to the urinary MDA
concentration, with larger spheres indicating higher MDA levels.
8-OHdG, 8-hydroxy-2′-deoxyguanosine; MDA, malondialdehyde.

Figure 4

Tissue concentrations of oxidative
stress markers at 24 h after 7 Gy irradiation. Quantification of
(A) 8-OHdG (µmol/mg DNA) and (B) MDA (µM/U) in multiple organs.
Data are presented as the mean ± standard deviation. *P<0.05 vs.
0 Gy. 8-OHdG, 8-hydroxy-2′-deoxyguanosine; MDA,
malondialdehyde.

Figure 5

Release of oxidative metabolites from
bone marrow cell cultures. Freshly isolated bone marrow cells from
irradiated mice were cultured for 24 h, and the concentrations of
(A) 8-OHdG and (B) MDA in the culture supernatant were quantified.
Values are expressed per 5×106 cells (normalized to a
fixed number of cells). Data are presented as the mean ± standard
deviation. *P<0.05, **P<0.01 vs. 0 Gy (Tukey-Kramer multiple
comparison test). 8-OHdG, 8-hydroxy-2′-deoxyguanosine; MDA,
malondialdehyde.

Figure 6

DNA damage in irradiated bone marrow
cells assessed using the comet assay. Tail moment was measured in
cultured bone marrow cells 24 h after irradiation. Data are
presented as the mean ± standard deviation. *P<0.05 vs. 0 Gy
(Tukey-Kramer multiple comparison test).

Figure 7

Apoptosis and necrosis in BM cells
after X-irradiation. BM cells were collected 24 h after irradiation
of 8-week-old mice, stained with annexin V-FITC and PI, and
analyzed by flow cytometry. (A) Representative quadrant dot plots.
(B) Quantification of annexin V+/PI+ (late
apoptotic) populations. Data are presented as the mean ± standard
deviation. *P<0.05 vs. 0 Gy (Tukey-Kramer multiple comparison
test). BM, bone marrow.
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Copy and paste a formatted citation
Spandidos Publications style
Monzen S, Terada K, Tawata Y, Sato T, Kousaka N and Mariya Y: Urinary 8‑OHdG and MDA as rapid biodosimetry markers in the lethal/sublethal dose range. Mol Med Rep 33: 174, 2026.
APA
Monzen, S., Terada, K., Tawata, Y., Sato, T., Kousaka, N., & Mariya, Y. (2026). Urinary 8‑OHdG and MDA as rapid biodosimetry markers in the lethal/sublethal dose range. Molecular Medicine Reports, 33, 174. https://doi.org/10.3892/mmr.2026.13884
MLA
Monzen, S., Terada, K., Tawata, Y., Sato, T., Kousaka, N., Mariya, Y."Urinary 8‑OHdG and MDA as rapid biodosimetry markers in the lethal/sublethal dose range". Molecular Medicine Reports 33.6 (2026): 174.
Chicago
Monzen, S., Terada, K., Tawata, Y., Sato, T., Kousaka, N., Mariya, Y."Urinary 8‑OHdG and MDA as rapid biodosimetry markers in the lethal/sublethal dose range". Molecular Medicine Reports 33, no. 6 (2026): 174. https://doi.org/10.3892/mmr.2026.13884
Copy and paste a formatted citation
x
Spandidos Publications style
Monzen S, Terada K, Tawata Y, Sato T, Kousaka N and Mariya Y: Urinary 8‑OHdG and MDA as rapid biodosimetry markers in the lethal/sublethal dose range. Mol Med Rep 33: 174, 2026.
APA
Monzen, S., Terada, K., Tawata, Y., Sato, T., Kousaka, N., & Mariya, Y. (2026). Urinary 8‑OHdG and MDA as rapid biodosimetry markers in the lethal/sublethal dose range. Molecular Medicine Reports, 33, 174. https://doi.org/10.3892/mmr.2026.13884
MLA
Monzen, S., Terada, K., Tawata, Y., Sato, T., Kousaka, N., Mariya, Y."Urinary 8‑OHdG and MDA as rapid biodosimetry markers in the lethal/sublethal dose range". Molecular Medicine Reports 33.6 (2026): 174.
Chicago
Monzen, S., Terada, K., Tawata, Y., Sato, T., Kousaka, N., Mariya, Y."Urinary 8‑OHdG and MDA as rapid biodosimetry markers in the lethal/sublethal dose range". Molecular Medicine Reports 33, no. 6 (2026): 174. https://doi.org/10.3892/mmr.2026.13884
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