MiRNA biomarkers for radiation biodosimetry
Disclosed herein are miRNA biomarkers and methods for measuring exposure of a mammalian subject to ionizing radiation using a cell-free biological sample. Also disclosed are dosimeters and methods for triaging and treating a subject exposed to ionizing radiation.
1. A method for measuring exposure of a human subject to ionizing radiation and administering a treatment method according to results thereof, comprising
(a) assaying a cell-free blood sample from a human subject exposed to radiation to measure the levels of miR-150;
(b) assaying the sample to measure the levels of miR-23a;
(c) normalizing the miR-150 levels based specifically on the miR-23a levels;
(d) estimating the measure of ionizing radiation exposure from the normalized miR-150 levels;
(e) identifying a human subject exposed to a remediable level of radiation poisoning, and
(f) administering to the human subject exposed to a remediable dose of radiation poisoning an immune modulator or mitigator according to level of radiation exposure.
2. The method of claim 1 , wherein the levels of miR150 are a measure of hematologic effects from ionizing radiation exposure.
3. The method of claim 1 , further comprising assaying the sample to measure the levels of miR-16 whose presence in the sample is an indication of hemolysis contamination, wherein hemolysis contamination is an indication that the sample should be discarded.
4. The method of claim 1 , further comprising spiking the sample with known amounts of at least one oligonucleotide, and determining in the sample levels of the at least oligonucleotide to further normalize the miR-150 levels.
5. The method of claim 1 , wherein the human subject has been exposed to remediable doses of ionizing radiation.
6. The method of claim 1 , wherein the cell-free blood sample comprises serum or plasma.
7. The method of claim 1 , further comprising assaying the sample to measure the levels of miRNA-25 whose presence in the sample is an indication of hemolysis contamination, wherein hemolysis contamination is an indication that the sample should be discarded.
8. The method of claim 1 , further comprising assaying the sample to measure the levels of miRNA-93 whose presence in the sample is an indication of hemolysis contamination, wherein hemolysis contamination is an indication that the sample should be discarded.
9. The method of claim 1 , further comprising assaying the sample to measure the levels of miRNA-106b whose presence in the sample is an indication of hemolysis contamination, wherein hemolysis contamination is an indication that the sample should be discarded.
10. The method of claim 1 , further comprising assaying the sample to measure the levels of miR-451 whose presence in the sample is an indication of hemolysis contamination, wherein hemolysis contamination is an indication that the sample should be discarded.
11. The method of claim 1 , wherein the immune modulator or mitigator is a hematopoietic stem cell transplant, antibiotic, a blood transfusion, or administration of growth factors.
12. The method of claim 11 , wherein the growth factor is GM-CSF.