Abstract

Many reports have demonstrated that radiation stimulates reactive oxygen species (ROS) production by mitochondria for a few hours to a few days after irradiation. However, these studies were performed using cell lines, and there is a lack of information about redox homeostasis in irradiated animals and humans. Blood redox homeostasis reflects the body condition well and can be used as a diagnostic marker. However, most redox homeostasis studies have focused on plasma or serum, and the anti-oxidant capacity of whole blood has scarcely been investigated. Here, we report changes in the anti-oxidant capacity of whole blood after X-ray irradiation using C57BL/6 J mice. Whole-blood anti-oxidant capacity was measured by electron spin resonance (ESR) spin trapping using a novel spin-trapping agent, 2-diphenylphosphinoyl-2-methyl-3,4-dihydro-2H-pyrrole N-oxide (DPhPMPO). We found that whole-blood anti-oxidant capacity decreased in a dose-dependent manner (correlation factor, r > 0.9; P < 0.05) from 2 to 24 days after irradiation with 0.5–3 Gy. We further found that the red blood cell (RBC) glutathione level decreased and lipid peroxidation level increased in a dose-dependent manner from 2 to 6 days after irradiation. These findings suggest that blood redox state may be a useful biomarker for estimating exposure doses during nuclear and/or radiation accidents.

Highlights

  • Biodosimetry is essential for estimating ionizing radiation exposure after large-scale radiological and/or nuclear incidents

  • We evaluated the correlations between signal intensity and the number of white blood cells (WBCs) and red blood cell (RBC) in twelve mice and found that the signal intensity decreased as the number of RBCs increased (Fig. S2c)

  • These results suggested that RBCs or their constituents strongly affect the signal intensity

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Summary

Introduction

Biodosimetry is essential for estimating ionizing radiation exposure after large-scale radiological and/or nuclear incidents. Chaleckis et al.[9] evaluated young and elderly human RBCs for plasma metabolites by liquid chromatography-mass spectrometry and demonstrated that 6 of 14 age-related metabolites were enriched in RBCs, including the redox-related metabolites oxidized glutathione (GSSG), NAD+, and NADP+. These findings suggested that RBC redox state is an important marker for health and body condition. RBC glutathione and plasma hydroperoxide levels were partly altered in association with whole-blood anti-oxidant capacity. These findings suggest that redox-related markers may be useful biomarkers for estimating exposure doses during nuclear and/or radiation accidents. The low anti-oxidant capacity persisted for at least 50 days after irradiation with ≥2 Gy, suggesting that it may contribute to the pathogenesis of radiation-related late effects, such as carcinogenesis, cataracts, and arteriosclerosis, which are closely related to oxidative stress[10,11,12]

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