Induction of oxidative stress biomarkers following whole-body irradiation in mice

PLoS One. 2020 Oct 1;15(10):e0240108. doi: 10.1371/journal.pone.0240108. eCollection 2020.

Abstract

Dose assessment is an important issue for radiation emergency medicine to determine appropriate clinical treatment. Hematopoietic tissues are extremely vulnerable to radiation exposure. A decrease in blood cell count following radiation exposure is the first quantitative bio-indicator using hematological techniques. We further examined induction of oxidative stress biomarkers in residual lymphocytes to identify new biomarkers for dosimetry. In vivo whole-body radiation to mice exposed to 5 Gy significantly induces DNA double-strand breaks, which were visualized by γ-H2AX in mouse blood cells. Mouse blood smears and peripheral blood mononuclear cells (PBMC) isolated from irradiated mice were used for immunostaining for oxidative biomarkers, parkin or Nrf2. Parkin is the E3 ubiquitin ligase, which is normally localized in the cytoplasm, is relocated to abnormal mitochondria with low membrane potential (ΔΨm), where it promotes clearance via mitophagy. Nrf2 transcription factor controls the major cellular antioxidant responses. Both markers of oxidative stress were more sensitive and persistent over time than nuclear DNA damage. In conclusion, parkin and Nrf2 are potential biomarkers for use in radiation dosimetry. Identification of several biological markers which show different kinetics for radiation response is essential for radiation dosimetry that allows the assessment of radiation injury and efficacy of clinical treatment in emergency radiation incidents. Radiation-induced oxidative damage is useful not only for radiation dose assessment but also for evaluation of radiation risks on humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis
  • DNA Breaks, Double-Stranded / radiation effects
  • Leukocytes, Mononuclear / pathology
  • Leukocytes, Mononuclear / radiation effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / analysis*
  • Oxidative Stress / radiation effects*
  • Ubiquitin-Protein Ligases / analysis*
  • Whole-Body Irradiation / adverse effects*

Substances

  • Biomarkers
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Ubiquitin-Protein Ligases
  • parkin protein

Grants and funding

The work was funded by a grant from the JSPS KAKENHI Grant Number 18H03377, Research on Health effects of radiation organized by the Japanese Ministry of the Environment, Industrial Disease Clinical Research Grants from the Japanese Ministry of Health, Labour, and Welfare and in part by NIFS Collaborative Research Program (NIFS13KOBA028). This work was performed at the Joint Usage/Research Center (Radiation Biology Center), Kyoto University, and the Program of the network-type joint Usage/Research Center for Radiation Disaster Medical Science of Hiroshima University, Nagasaki University, and Fukushima Medical University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.