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Protein Tinkering Allows Radiation-Dose Recovery

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Boosting a protein response in intestinal cells helps mice survive potentially fatal doses of radiation, according to a new study by researchers in the radiation oncology department of the Stanford University School of Medicine.

The procedure offers at least partial protection even if administered up to 24 hours after radiation exposure. So it might not only help patients recover from therapeutic radiation treatments but also protect first responders during a nuclear accident or attack. Amato J. Giaccia, PhD, senior author of the study, said the researchers didn’t expect it to be so effective, especially because it doesn’t shield against radiation damage but only helps promote repair:

We were very surprised by the amount of protection the animals received. 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.

Dr. Giaccia is the Jack, Lulu and Sam Willson Professor of Radiation Oncology at the medical school. He was quoted in a school news release. A research article about the study was published last week in Science Translational Medicine.

The researchers used two different methods, genetic engineering and administration of a drug, to boost the activity of certain proteins, called HIF1 and HIF2, that cells produce during hypoxic conditions. HIF proteins help the intestine absorb nutrients, block pathogens, and maintain healthy fluid exchange.

Apparently, HIF proteins—specifically, the researchers discovered, HIF2—can protect against radiation damage as well oxygen shortages. Among the genetically modified mice, 70 percent lived at least 30 days after receiving a normally fatal dose of abdominal radiation, and 27 percent survived at least that long after a normally fatal dose of whole-body radiation. Among mice who received the drug instead, 67 percent lived for at least 60 days after a normally lethal abdominal dose, and 40 percent lived for at least 30 days after a normally lethal whole-body dose.

No control mice lived longer than 10 days.

“The animals that survived the abdominal radiation have a life span that is similar to unexposed animals, which was very exciting to us,” Dr. Giaccia said. “However, we realized it would be impossible to pretreat humans unexpectedly exposed to large amounts of radiation like at Chernobyl or Fukushima because those exposures are, by nature, unpredictable.”

So the researchers tried giving the drug to genetically normal mice after radiation exposure. It still helped when administered up to 24 hours after the radiation dose. For example, when it was given four hours after exposure to abdominal radiation, 45 percent of treated animals but no untreated animals survived at least 10 days.

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