If you’re exposed to radiation from a dirty bomb or a nuclear reactor meltdown, it’s not easy for doctors to quickly determine how badly you’ve been hurt. Even serious radiation damage isn’t immediately apparent. Now, researchers say they’ve hit upon a possible rapid diagnostic test, one that looks for changes in small molecules known as microRNAs that circulate in the blood. The advance could help doctors identify and treat victims before telltale symptoms appear.
MicroRNAs, or miRNAs, play a key role in processes that turn genes on and off. Researchers hope the molecules will someday prove useful as biological markers of cardiovascular disease, diabetes, and certain cancers. MiRNAs might also help track the effectiveness of treatments.
Several groups previously reported that an analysis of miRNAs circulating in blood can indicate radiation exposure. A team led by Dipanjan Chowdhury at Harvard Medical School's Dana-Farber Cancer Institute in Boston set out to take that finding a step further and see if miRNA analysis could also indicate the extent of radiation damage and predict survival.
The researchers subjected mice to three levels of whole-body radiation—low and high survivable doses and a deadly blast. They drew blood within 24 hours of irradiation. They also collected blood and bone marrow samples at 7, 15, 30, and 90 days to check white blood cell counts and other indicators of the health of the hematopoietic system—blood and the organs that make it—which is known to fail after heavy irradiation.
The team identified 170 miRNAs and zeroed in on five that showed a recognizable pattern. The mice getting the highest dose had a markedly lower concentration of one of those five miRNAs and significantly higher levels of the other four as compared with the animals that got less radiation, the team reports online today in Science Translational Medicine. The miRNA analysis could distinguish between different radiation doses within 24 hours of exposure, even though damage to white blood cells and bone marrow was not seen until 15 days after irradiation.
The researchers used the same miRNA analysis to show that a bone marrow transplant rescued mice with what would have been lethal radiation exposure. An early diagnosis could help doctors decide whether to try a bone marrow replacement or other treatments before the damage spreads to other organs.
It's "an interesting paper” and significant that miRNA analysis can predict survival, says David Brenner, a radiation biophysicist at Columbia University Medical Center. In case of an accident or attack, he says, "it would help focus potentially scarce medical resources on those people who needed them most." MiRNA analysis could be particularly valuable for indicating the degree of damage to the individual's hematopoietic system, which is more important for assessing treatment options than simply measuring the radiation dose, says Yoshihisa Matsumoto, a radiation biologist at the Tokyo Institute of Technology.
Both scientists caution there is still a lot of work needed to turn the finding into a diagnostic test. The first hurdle is confirming that the same or similar miRNAs can be found in humans. Another challenge is that miRNA patterns might change with time and vary with individuals, possibly lessening the accuracy of the analysis. Another limitation is that this test applies only to acute radiation sickness, not to the possibility of developing cancer in the long term.
Chowdhury is well aware of these issues and emphasizes that his team’s study is a first step. "Our focus right now is to see if these findings are relevant in humans," he says. The team is hoping to collaborate with institutions that have collected samples from radiation accident victims.