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Small molecule may protect against radiation exposure, say Stanford scientists

Small molecule may protect against radiation exposure, say Stanford scientists

P1060359No one wants to imagine a nuclear accident. But, as Fukushima and Chernobyl showed, they do happen. Unfortunately there’s no truly effective way to protect people who have been exposed to large amounts of radiation (more than 10 gray, for those of you wondering; for you overachievers out there, 1 gray is the absorption of 1 joule of radiation energy per kilogram of matter).

Many of these people will die from what’s known as radiation-induced gastrointestinal syndrome when the rapidly dividing cells in their intestinal lining begin to die. As a result, the intestine loses its ability to regulate fluid loss and prevent the entry of pathogens into the body, causing severe diarrhea, electrolyte imbalance and sepsis.

Stanford radiation oncologist Amato Giaccia, PhD, and his colleagues wondered whether a cellular pathway that controls how cells respond to stress could be involved in the intestine’s response to radiation. Their study was featured today on the cover of Science Translational Medicine. As I explain in our release:

The researchers were studying a molecular pathway involved in the response of cells to conditions of low oxygen called hypoxia. Hypoxic cells produce proteins known as hypoxia-inducible factors, which help the cells survive the stressful conditions. (The HIF proteins – HIF1 and HIF2 – are normally degraded quickly when oxygen levels are normal.)

Hypoxia often occurs in fast-growing solid tumors as cells find themselves far from oxygen-delivering blood vessels, but it can also occur during times of inflammation, or in tissues like the intestine that experience natural gradations in oxygen levels. HIF proteins help the intestine absorb needed nutrients while blocking the entry of pathogens and maintaining healthy fluid exchange.

Giaacia and lead study author Cullen Taniguchi, MD, PhD, a postdoctoral scholar, wondered if increasing the levels of HIF proteins in intestinal epithelial cells could help the them survive damaging amounts of radiation. To test their theory, they used a small molecule called DMOG to block the naturally occurring degradation of HIF proteins in laboratory mice exposed to radiation. They found that administering DMOG to the mice significantly increased their survival – even when the molecule was given 24 hours after initial exposure.

The study suggests it may one day be possible to prevent or reduce the incidence of  radiation-induced gastrointestinal syndrome in humans.  It also provides an intriguing hint that it may be possible to mitigate some of the gastrointestinal side effects experienced by patients undergoing radiation therapy for cancer.

More from our release:

Although the study suggests a possible way to mitigate the effects of therapeutic radiation exposure, much work remains to be done, the researchers caution. For one thing, 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. But the next steps are clear.

“There are a number of drug molecules that act in a manner similar to DMOG that are already in clinical trials for unrelated conditions,” said Giaccia. “Our next step will be to test some of these molecules to see if they also offer radioprotection.”

Previously: Stanford scientists measure health effects of the Fukushima Daiichi nuclear accident, Radiation expert to Fukushima: Don’t worry, be happy? and Potential anti-cancer therapy starves cancer cells of glucose
Photo by Martin Dougiamas

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