Abstract
The risk of radiation exposure, due to accidental or malicious release of ionizing radiation, is a major public health concern. Biomarkers that can rapidly identify severely-irradiated individuals requiring prompt medical treatment in mass-casualty incidents are urgently needed. Stable blood or plasma-based biomarkers are attractive because of the ease for sample collection. We tested the hypothesis that plasma miRNA expression profiles can accurately reflect prior radiation exposure. We demonstrated using a murine model that plasma miRNA expression signatures could distinguish mice that received total body irradiation doses of 0.5 Gy, 2 Gy, and 10 Gy (at 6 h or 24 h post radiation) with accuracy, sensitivity, and specificity of above 90%. Taken together, these data demonstrate that plasma miRNA profiles can be highly predictive of different levels of radiation exposure. Thus, plasma-based biomarkers can be used to assess radiation exposure after mass-casualty incidents, and it may provide a valuable tool in developing and implementing effective countermeasures.
Highlights
In the event of an improvised nuclear device attack or disaster in a nuclear power plant, hundreds of thousands of people may be exposed to various doses of radiation
Exposure to ionizing radiation is associated with induction of acute radiation syndrome (ARS), known as radiation sickness, which is characterized by nausea, vomiting, diarrhea, skin damage, and can include loss of bone marrow, internal bleeding, and death
Using a murine model of single exposure total body irradiation (TBI), we investigated whether circulating miRNA in plasma can differentiate exposure to radiation doses of 2 Gy and higher and developed a normalization strategy to analyze the data
Summary
In the event of an improvised nuclear device attack or disaster in a nuclear power plant, hundreds of thousands of people may be exposed to various doses of radiation. Exposure to ionizing radiation is associated with induction of acute radiation syndrome (ARS), known as radiation sickness, which is characterized by nausea, vomiting, diarrhea, skin damage, and can include loss of bone marrow, internal bleeding, and death. Depending on the exposure dose, the symptoms of ARS can appear within hours to weeks. Subjects receiving doses less than 2 Gy are asymptomatic or have mild symptoms; subjects receiving doses from 2 to 6 Gy need immediate care, with variable survival prognoses; and radiation doses .6. The hematopoietic system syndrome appears in weeks to 2 months and mortality can occur within 1 month; at doses of 8 Gy to 12 Gy, gastrointestinal effects occur within a week after the exposure and death can occur within 10 days; at doses .15. At doses .2 Gy, the hematopoietic system syndrome appears in weeks to 2 months and mortality can occur within 1 month; at doses of 8 Gy to 12 Gy, gastrointestinal effects occur within a week after the exposure and death can occur within 10 days; at doses .15 Gy, the central nervous system will be affected and fatalities can occur within 2 days [2]
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