Lethal radiation exposure may seem the stuff of science fiction. But workers at nuclear power plants and people who witnessed the aftermath of the atomic bombs dropped on Japan in 1945 are certainly aware of the real-world dangers.
Now Stanford researchers have hit upon a way to possibly protect people after exposure to high doses of radiation by blocking the degradation of a small molecule in their intestinal tracts. The molecule, called HIF2, helps cells respond to stress. The approach worked unexpectedly well in laboratory mice.
The side effects of acute radiation exposure are most evident in rapidly dividing cells in the intestinal lining or bone marrow. Exposure leads to debilitating nausea, vomiting and diarrhea, and high risk of infection. Though bone marrow transplant can mitigate the bone marrow damage, there’s no treatment for the intestinal impact.
When the researchers studied the effect of total body irradiation on mice in which HIF2 degradation had been blocked, they found that over one-third survived at least 30 days — as long as they also received a bone marrow transplant. In contrast, none of the untreated mice lived longer than 10 days after exposure.
The animals were still at least partially protected from death even when the treatment was initiated up to 24 hours after radiation exposure.
Though they haven’t tested it yet, the researchers hope a strategy like theirs, which protects HIF2 with a molecule called DMOG, will relieve cancer patients from diarrhea and nausea caused by radiation therapy.
“There are a number of drug molecules that act in a manner similar to DMOG that are already in clinical trials for unrelated conditions,” says professor of radiation oncology Amato Giaccia, PhD, who led the study. “Our next step will be to test some of these molecules to see if they also offer radioprotection.”