radiation recovery. drugs could one day help save the lives of those who were exposed to high levels of radiation, as in the case of a nuclear accident.
Kimimasa Mayama / Reuters
He can not work against Godzilla, but a new drug could protect people against lethal doses of radiation. The compound already in clinical trials for treating a blood disorder, may also make radiation therapy for safer cancer.
"What's really exciting about this work is that they not only found this against measure to mitigate radiation-induced [damage], but the fact that it works in a time window 24 hours after exposure, "says oncologist David Kirsch of Duke University Medical Center in Durham, North Carolina.
radiation first strikes the bone marrow, wiping the production of cells important to the fight against infections, clotting, and to carry oxygen through the body in the blood. at high levels, radiation chips and the gastrointestinal tract and damage the outer layers of the intestine and colon, and causing fluid loss, diarrhea, vomiting and local infections, which can become systemic and lead to death. the condition is known as the gastrointestinal syndrome induced by radiation (RIGS), and n ' there are no approved drugs to treat it.
Researchers have suspected that two proteins called hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2) play a role in maintaining the integrity of the gut during different periods of stress. To test whether they were related to RIGS, Amato Giaccia radiation oncologist at the School of Medicine of Stanford University in California engineered mice lacking a protein called PHD family that normally destabilize HIF-1 and HIF-2. Without PHD, mice have levels higher HIF protein than usual. While normal mice all died within 10 days of exposure to high radiation dose for the abdomen, 70% of mice lacking PHD were alive after 30 days. "We were very surprised by the magnitude of the response," said Giaccia.
Next, the team tried to replicate the results with a drug. They turned to dimethyloxalylglycine (DMOG), a compound known to block the PHD proteins and already in clinical trials to treat chronic anemia. as mice lacking PHD, the animals that received a dose of DMOG-even 24 hours after exposure to radiation-survived longer than usual. Two thirds of them were still alive 60 days after exposure, today reports the team in Science Translational Medicine . DMOG did not change the initial damage to the gastrointestinal tract by the radiation, but it helped the gut recover. Boosted levels of HIF protein in particular, HIF-2α, the researchers showed, were the key to recovery.
"what we do with DMOG is that we change the physiology of normal tissue allow time to repair and regenerate," Giaccia said.
new discoveries, Kirsch says, point to an intervention that could be given within 24 hours of an emergency radiation such as fusion nuclear reactors in Fukushima, Japan, in 2011, to save lives.
Giaccia also asked whether the results can benefit cancer patients. DMOG as a drug, he said, could facilitate the toxicity accompanying radiotherapy. Patients taking this could also tolerate higher doses of radiation, applied more widely throughout the body, killing cancer cells than current methods.
But Kirsch warns that it is too early to say whether DMOG or other PHD-blocking drugs, can be used in patients with cancer. "There is some literature suggesting that targeting the HIF pathway may actually protect tumor radiation," he said, which would be against-productive. "Further studies should be done to show that these compounds did not affect tumor response."
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