Abstract
For effective medical management of radiation-exposed persons after a radiological/nuclear event, blood-based screening measures in the first few days that could predict hematologic acute radiation syndrome (HARS) are needed. For HARS severity prediction, we used microRNA (miRNA) expression changes measured on days one and two after irradiation in a baboon model. Eighteen baboons underwent different patterns of partial or total body irradiation, corresponding to an equivalent dose of 2.5 or 5 Gy. According to changes in blood cell counts (BCC) the surviving baboons (n = 17) exhibited mild (H1-2, n = 4) or more severe (H2-3, n = 13) HARS. In a two Stage study design we screened 667 miRNAs using a quantitative real-time polymerase chain reaction (qRT-PCR) platform. In Stage II we validated candidates where miRNAs had to show a similar regulation (up- or down-regulated) and a significant 2-fold miRNA expression difference over H0. Seventy-two candidate miRNAs (42 for H1-2 and 30 for H2-3) were forwarded for validation. Forty-two of the H1-2 miRNA candidates from the screening phase entered the validation step and 20 of them showed a statistically significant 2–4 fold up-regulation relative to the unexposed reference (H0). Fifteen of the 30 H2-3 miRNAs were validated in Stage II. All miRNAs appeared 2–3 fold down-regulated over H0 and allowed an almost complete separation of HARS categories; the strongest candidate, miR-342-3p, showed a sustained and 10-fold down-regulation on both days 1 and 2. In summary, our data support the medical decision making of the HARS even within the first two days after exposure where diagnostic tools for early medical decision are required but so far missing. The miRNA species identified and in particular miR-342-3p add to the previously identified mRNAs and complete the portfolio of identified mRNA and miRNA transcripts for HARS prediction and medical management.
Highlights
In a large-scale radiological emergency, early detection of exposed individuals would be required in order to evaluate the extent of radiation injuries and, as necessary, providePLOS ONE | DOI:10.1371/journal.pone.0165307 November 15, 2016Early Prediction of hematologic acute radiation syndrome (HARS) Using MicroRNA Expression appropriate treatment [1]
We investigated whether there were potential regulatory interactions between the 33 HARS specific non-coding miRNAs identified in this study and the 29 coding genes with HARS associated regulation, which we defined in our previous study [15]
Based on changes of the lymphocyte, granulocyte and thrombocyte counts examined 7–203 days after exposure, HARS scores were determined according to the criteria of METREPOL
Summary
In a large-scale radiological emergency, early detection of exposed individuals would be required in order to evaluate the extent of radiation injuries and, as necessary, provide. Prediction of HARS Using MicroRNA Expression appropriate treatment [1]. Estimates of the absorbed dose aid in determining risk for later occurring acute (up to 60 days after irradiation) or chronic (months and years after irradiation) health effects. 2 Gy single whole body dose), severe acute health effects (acute radiation syndrome, ARS) will occur and early diagnosis within 1–3 days after exposure is essential to hospitalize exposed individuals in specialized clinics and to quickly initiate appropriate treatment. Treatment with cytokines (Granulocyte-Colony Stimulating Factor (G-CSF)) should start within the first day after exposure and appropriate diagnostic tools are required and missing ([2],[3]). It is important to identify the few highly exposed individuals from among many who believe they were exposed (the worried well), to avoid depletion of clinical resources
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