New drug may help people survive radiation exposure

A new drug being developed to treat anemia and other conditions might help people survive deadly doses of radiation in the event of a radiation accident such as the Chernobyl nuclear disaster in 1986, U.S. researchers said Wednesday. Researchers at the Stanford University School of Medicine said they have observed the protective effects of the drug, known as DMOG, when it is given up to 24 hours after exposure, which makes it a promising treatment for people unintentionally exposed to large amounts of radiation. The findings, published in the U.S. journal Science Translational Medicine, may also make radiation therapy for cancer patients safer. According to the researchers, exposure to a nuclear accident may cause acute radiation syndrome, also known as "radiation sickness," in which high doses damage vital organs, including the bone marrow and the gastrointestinal tract. Although radiation's effects on the bone marrow can be mitigated by a bone marrow transplant, there's no treatment for its effects on the gastrointestinal tract, which include rapid water loss, diarrhea, vomiting and nausea, typically followed by death within two weeks of exposure. In the new study, the researchers suspected that two proteins, known as HIF1 and HIF2, would protect mice against radiation injury to the gastrointestinal tract. Because the stability of the proteins is negatively controlled by an enzyme called PHD, they first used genetically engineered mice to delete PHDs specifically and found that the levels of HIF1 and HIF2 proteins increased significantly. Furthermore, 70 percent of the genetically modified mice lived for at least 30 days after receiving a normally lethal dose of abdominal radiation, and 27 percent survived at least 30 days after a normally lethal dose of whole-body radiation, a situation which more closely mimics accidental human exposure. Next, they treated unmodified mice with the drug DMOG, which is known to inhibit the activity of the two proteins, prior to radiation exposure. They found that 67 percent of the treated mice survived for at least 60 days after receiving a normally lethal dose of abdominal radiation, and that 40 percent lived for at least 30 days after a normally lethal dose of whole-body radiation. In both cases, normal mice all died within 10 days after either type of radiation exposure. Further experiments showed that HIF2, rather than HIF1, is responsible for the radioprotection observed in the study. The researchers also experimented with treating the mice with DMOG after radiation exposure. They found that they were "still able to rescue a significant proportion of the animals" even when the drug was given 24 hours after exposure. "We were very surprised by the amount of protection the animals received," Amato Giaccia, professor of radiation oncology at Stanford said in a statement. "The important thing to note is that we didn't change the amount of damage the intestinal cells sustained as a result of the radiation; we simply changed the physiology of that tissue and how it responded to that damage." But the researchers cautioned that much work remains to be done as mice are more resistant to the effects of radiation than humans, and the radiation doses used in the study far exceed what would be used to treat a cancer patient. "However, even if DMOG itself turns out to be unsuitable for human use, the understanding of its mechanism .. will be invaluable for developing future treatments to protect human patients from radiation," said an editor's summary accompanying the paper.