Study points to therapy for radiation sickness

January 25, 2012

(Medical Xpress) -- A combination of two drugs may alleviate radiation sickness in people who have been exposed to high levels of radiation, even when the therapy is given a day after the exposure occurred, according to a study led by Harvard Medical School researchers at Dana-Farber Cancer Institute and Children’s Hospital Boston.

Mouse studies of other potential therapies suggest they would be effective in humans only if administered within a few minutes or hours of radiation exposure, making them impractical for use in response to events involving mass casualties. In contrast, the larger time window for administering the two-drug regimen raises the prospect that it could become a mainstay of the response to public health threats such as a nuclear power plant accident or nuclear terror attack.

In a paper published online by the journal Science Translational Medicine, the scientists report the beneficial effects, in mice, of a combination of a fluoroquinolone antibiotic (similar to the commonly used human antibiotic ciprofloxacin, or “Cipro”) and a synthetic version of the natural human infection-fighting protein BPI. Mice that received the combination a day after being exposed to high doses of radiation fared far better than mice that received neither or only one of the agents. Whereas radiation exposures of that magnitude almost always prove fatal within a month, 80 percent of the mice that received the two agents were alive and apparently healthy a month into the study.

Faster rebound

The study’s lead author is Eva Guinan, HMS associate professor of radiation oncology at Dana-Farber, and the senior author is Ofer Levy, HMS assistant professor of pediatrics at Children’s Hospital Boston.
The investigators also found that the ability to generate new blood cells — which can shut down in the aftermath of radiation exposure — rebounded much more quickly and vigorously in the mice treated with fluoroquinolone and rBPI21 (the synthetic version of BPI), potentially contributing to their return to health.

“Both fluoroquinolone antibiotics and rBPI21 have been shown to be quite safe in humans,” said Levy. “Their combined effectiveness in our study involving mice is an indication that they may be equally beneficial in people.”

The research potentially represents a major step in the United States government’s efforts to build a stockpile of therapies to counter radiological dangers.

“There is great interest in creating systems for dealing with the short- and long-term health risks of a significant release of radiation, whether from an accident at a nuclear power plant, an act of terrorism or even a small-scale incident in which a CT machine malfunctions,” said Guinan. “Developing useful agents has proven difficult. Most existing drugs aren’t effective enough and must be given within a very short time frame to provide any benefit. The recent disaster at the Fukushima nuclear power plant in Japan illustrates the need for agents that can be deployed rapidly to treat large populations.”

Severe effects

, also known as acute radiation syndrome, varies with the amount of radiation an individual receives. The first signs of the disease usually are nausea and vomiting, which can be followed by fever, dizziness, weakness, bloody vomit and stools, difficulty breathing and infection. The body’s blood-making tissue, nervous system, digestive tract, lungs and cardiovascular system all can be affected. At very high doses, radiation is usually fatal.

Within the body, the effects of heavy radiation may include leakage of bacteria and the toxins they produce into the bloodstream from the digestive tract or through broken skin. Radiation effects wreak havoc with the function of the heart and lungs, disrupt the process of blood coagulation and inflame tissue throughout the body.

When bacteria or certain toxins enter the blood under normal conditions, the body’s immune system responds by dispatching neutrophils — white blood cells­ — to destroy the intruders. The neutrophils release a payload of BPI (bactericidal/permeability-increasing protein), which sticks tightly to molecules called endotoxins on the surface of the bacteria. The binding not only helps BPI kill the bacteria but also blocks inflammation caused by live or dead bacteria­ — something that conventional antibiotics do not do.

When a person is exposed to high levels of radiation, however, the ability to generate neutrophils is almost obliterated. “It’s a perfect storm of disease-causing events,” Guinan said. “Radiation results in bacteria and endotoxins entering the bloodstream at the same time that the body’s defenses are lowered.”

The treatment approach developed by Guinan, Levy and their colleagues takes direct aim at two potential contributors to radiation sickness: bacteria and the endotoxins on their surface. “We theorized that a two-drug therapy would be most effective,” Levy said. “Others had already shown some benefit to treatment with fluoroquinolones after ; at least part of the benefit came from killing bacteria in the blood. The second, rBPI21, would bind to, neutralize, and ‘mop up’ the endotoxins released by the dying bacteria, thereby removing the trigger of the inflammation process.”

Explore further: Study identifies possible therapy for radiation sickness

Related Stories

Study identifies possible therapy for radiation sickness

November 23, 2011
A combination of two drugs may alleviate radiation sickness in people who have been exposed to high levels of radiation, even when the therapy is given a day after the exposure occurred, according to a study led by scientists ...

Researchers successfully treat previously lethal doses of radiation

January 5, 2012
Multiple scenarios exist where warfighters may be exposed to high levels of radiation. Countermeasures against possible high doses of radiation are an ongoing high priority for Department of Defense research and development ...

Radiation response a meltdown in reason

July 14, 2011
The possibility that low doses of radiation may prevent or delay the progression of cancer is being explored by a Flinders University research team led by Professor Pam Sykes (pictured) in a move that runs counter to the ...

Deep-space travel could create heart woes for astronauts

April 7, 2011
(PhysOrg.com) -- Astronauts anticipate more trips to the moon and manned missions to Mars. But exposure to cosmic radiation outside the Earth’s magnetic field could be detrimental to their arteries, according to a study ...

Experts explain radiation risks - real and relative (w/ video)

August 15, 2011
What ills do we risk from radiation to which we are exposed naturally, by choice, or by accident? The question looms large in the aftermath of the meltdown of fuel rods from nuclear reactors at the Fukushima Daiichi power ...

Recommended for you

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

Liquid biopsy results differed substantially between two providers

December 14, 2017
Two Johns Hopkins prostate cancer researchers found significant disparities when they submitted identical patient samples to two different commercial liquid biopsy providers. Liquid biopsy is a new and noninvasive alternative ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.