Panel of Bloodstream MicroRNAs Predicts Damage from Radiation Exposure

A panel of microRNAs (miRNAs) that can be measured in blood samples is able to predict the extent of long-term radiation injury and likelihood of survival following exposure to high doses of radiation.

Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after exposure to high levels of radiation.

Investigators at Dana-Farber Cancer Institute (Boston, MA, USA) have identified serum miRNA signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure.

MiRNAs comprise a family of small noncoding 19- to 25-nucleotide RNAs that regulate gene expression by targeting mRNAs in a sequence specific manner, inducing translational repression or mRNA degradation, depending on the degree of complementarity between miRNAs and their targets. Many miRNAs are conserved in sequence between distantly related organisms, suggesting that these molecules participate in essential processes. In fact, miRNAs have been shown to be involved in the regulation of gene expression during development, cell proliferation, apoptosis, glucose metabolism, stress resistance, and cancer. MiRNAs are made in cells, but some may be detected in the bloodstream.

The investigators systematically assessed the impact of TBI on the bone marrow's blood-cell production system to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. In addition, they found that 68 of 170 miRNAs detected in blood serum changed with radiation exposure. This number was reduced to a panel that acted as a "signature" of radiation dose.

The investigators reported that mice exposed to sub-lethal (6.5 Gy) and lethal (8.0 Gy) doses of radiation were physically indistinguishable for three to four weeks after exposure. In contrast, a serum miRNA signature was detectable 24 hours after radiation exposure that consistently differentiated these two populations.

By using a radioprotective agent before exposure or radiation mitigation after lethal radiation, the investigators determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Finally, using humanized mice that had been engrafted with human CD34+ HSCs, they determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells.

"After a radiation release, there is currently no way to tell who was exposed and who was not, and if someone was exposed, is it lethal or not?" said senior author Dr. Dipanjan Chowdhury, a principal investigator in radiation oncology at Dana-Farber Cancer Institute. "Drugs that can limit bone marrow damage are available but, to be effective, must be given before the appearance of radiation symptoms."

The paper was published in the May 13, 2015, online edition of the journal Science Translational Medicine.

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Dana-Farber Cancer Institute