'Lethal' radiation doses can be treated with drugs

Mice can survive lethal effects of high radiation doses that are usually fatal when given a double-drug therapy ? even when they get the drugs 24 hours after exposure.

Because these drugs are known to be safe in people, it could be worth stockpiling them in preparation for a nuclear accident or terrorist attack, say the researchers behind the new study.

High doses of radiation harm the body, partly by damaging rapidly dividing cells, such as those in the intestine. The damage leaves the intestine leaky, allowing harmful bacteria to escape into the bloodstream ? consequently antibiotics may be used to treat individuals exposed to radiation.

Eva Guinan and Ofer Levy at Harvard Medical School and their colleagues have identified another approach to treatment involving a protein known as bactericidal/permeability-increasing protein (BPI), which plays a role in the immune response to the harmful bacteria from the intestine.

Guinan and Levy's team studied 48 people who were receiving radiation doses in preparation for a bone marrow transplant. Following radiation exposure, levels of BPI fell to an average of 71 times below normal levels. In 37 of the transplant patients the protein was undetectable. The team say this is probably due to damage to the bone marrow, which leaves it unable to produce enough of the white blood cells that normally encourage BPI production.

Survival boost

The team then used the information in the treatment of mice given a typically lethal dose of radiation. A day after exposure, some mice were given the oral antibiotic fluoroquinolone while some mice were given a combination of fluoroquinolone and injections of BPI. A third group had no treatment at all.

Most of the untreated mice died within 30 days. As expected, the antibiotic boosted the survival rate: around 40 per cent of the mice given the antibiotic were still alive after 30 days ? but survival rates jumped to almost 80 per cent in the mice given the combination therapy.

The two drugs are already known to be safe in healthy and sick humans. A radiation treatment based on the two is likely to be practical because both drugs can be stored for long periods of time and the mouse study suggests they would be effective even if administered 24 hours after exposure, says Levy. "Maybe there needs to be a stockpile of BPI in case, God forbid, there was another Fukushima," he says.

Don Jones at the University of Leicester, UK, finds the study "very exciting". "The therapy looks to be very effective at mitigating the effects of total body irradiation," he says.

Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.3003126

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