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Mouse Study Reveals Radiation Exposure-Related Blood MicroRNA Profiles

NEW YORK (GenomeWeb News) – MicroRNA markers in the blood may hold promise as a means of predicting ill health effects following exposure to ionizing radiation, according to a PLOS One study based on mouse models of radiation exposure.

"Our paper reports the identification of a panel of microRNA markers in mice whose serum levels provide an estimate of radiation response and of the dose received after an exposure has occurred," senior author Arnab Chakravarti, a radiation oncology researcher with Ohio State University's Comprehensive Cancer Center, said in a statement.

Chakravarti and colleagues from Ohio State University, Philadelphia's Wistar Institute, and NanoString Technologies relied on a quantitative, hybridization-based assay to track miRNA levels in blood samples taken from mice exposed to X-ray or gamma-ray radiation. One miRNA in particular — miR-150 — showed dips in expression that were especially pronounced after higher radiation doses. Other miRNAs showed dose-related expression jumps in blood samples from the irradiated animals.

If similar findings pan out in humans, study authors said, it's possible that one or more such miRNAs could serve as blood-based markers for so-called radiation biodosimetry, which aims to better assess risk after accidental exposure to ionizing radiation on the job or in the environment, for instance.

The availability of appropriate biomarkers is also expected to be useful for tracking treatment response — or perhaps curbing complications — during some cancer treatments that include irradiation.

"Biodosimetry is an emerging concept that could enable us to identify individuals who need immediate treatment after a radiation exposure and to better develop personalized radiation treatment plans for patients," Ohio State's Naduparambil Jacob, the first author on the PLOS One study, said in a statement.

In addition to acute radiation syndromes that can set in soon after some ionizing radiation exposure, the researchers said, several serious conditions such as degenerative disease and cancer may manifest themselves in radiation-exposed individuals further down the road.

The nature and severity of these complications can vary from one person to the next, but they typically depend on how much radiation is absorbed into the body. As such, investigators are keen to find straightforward and reliable ways of measuring radiation dose and effects within a given exposed individual.

"Development of robust biomarkers based on an individual's biological response is crucial for accurate assessment of the level of exposure and making important medical decisions," Chakravarti, Jacob, and co-authors argued, adding that "personalized assessment will allow evaluation of an individual's physiological response to radiation damage."

Suspecting that miRNA patterns in the blood could provide a window into such radiation effects, the researchers used an amplification-free, hybridization-based digital assay designed around NanoString Technologies' nCounter to assess levels of more than 600 miRNAs in blood samples from control mice or mice exposed to gamma- or X-ray radiation.

To normalize miRNA levels and more accurately measure miRNA shifts related to radiation dose and time following exposure, they also incorporated experiments involving so-called "spike-in" oligonucleotides.

Groups of at least five mice apiece were treated with single shots of gamma-ray radiation given at a range of doses. Another 15 animals were treated multiple times using X-rays — radiation exposures meant to resemble the fractionated radiation doses delivered prior to bone marrow transplant procedures.

When they assessed miRNA profiles in blood samples from each group of irradiated mice 24 hours, 48 hours, or 72 hours after exposure, the investigators saw a set of 88 miRNAs that seemed to show higher or lower expression following radiation.

From there, they narrowed in on some of the most promising candidate biomarker miRNAs, exploring the relationship between miRNA levels, radiation dose, time after exposure, and so on.

Of particular interest were miR-200b and miR-762, which were found at higher-than-usual levels in samples from radiation-exposed mice, and miR-150, which showed a dose-dependent decrease in expression after radiation treatment. In the case of miR-150, for instance, the team found clues that the dose-related drop in expression reflects radiation-induced damage to the hematopoietic system.

Additional research is needed to determine whether the same sorts of patterns occur in human blood samples following radiation exposure. But based on findings so far, the study's authors proposed that "[i]ndividual miRNAs such as miR-150 alone or in combination with other markers have the potential to estimate the dose to which the individual was exposed."

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