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.
Highlights
Accidental radiation exposure due to a nuclear accident or terrorism using radioactive materials may cause severe health effects in a large population
Biological dosimetry analysis is based on detection of cytogenetic damage in peripheral blood lymphocytes, such as dicentrics, translocations, and micronuclei
We found that combining γ-H2AX, parkin, and Nrf2 biomarkers may be useful for extending dose assessment time after emergency radiation incidents
Summary
Accidental radiation exposure due to a nuclear accident or terrorism using radioactive materials may cause severe health effects in a large population. Triage of the radiation victims is a major concern in the event of a large-scale radiological emergency. Requirements for preparedness planning for radiation emergencies have been discussed [1]. Dosimetry is an important issue for radiation emergency medicine to provide appropriate strategies for clinical treatment [2]. The cytogenetic assay is the international gold-standard method for biological dosimetry [3]. Biological dosimetry analysis is based on detection of cytogenetic damage in peripheral blood lymphocytes, such as dicentrics, translocations, and micronuclei.
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