Beryllium's cellular assault

Contact: Kevin Roark, knroark@lanl.gov, (505) 665-0582 (02-095)

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LOS ALAMOS, N.M., Aug. 22, 2002 -- Researchers at Los Alamos National Laboratory, seeking to better understand the pathology of Chronic Beryllium Disease are studying the fundamental properties of metal interaction with carboxylate molecules, carbon/oxygen structures that are common in the body, to better understand how metals, specifically beryllium in water solution, might attack human cells.

The latest research into beryllium carboxylates will be the subject of a talk by Erik Brady, a post-doc in Los Alamos’ Chemistry Division, Actinide, Catalysis and Separations group, at the 2002 American Chemical Society meeting in Boston, Aug. 22 at 2:10 p.m. in room 310 of the Boston Convention Center.

The chemical structure of beryllium acetate, a type of beryllium carboxylate. The structure is determined using X-ray crystallography.

Beryllium is a silver-gray, nonradioactive metal that is extremely light and very stable. It is lighter than aluminum, yet one and a half times stiffer than steel. Beryllium is used in satellite guidance systems, spacecraft, optical instruments, nuclear reactors and golf clubs. At Los Alamos, beryllium is used in nuclear weapons research and stockpile stewardship.

In certain individuals, breathing tiny beryllium particles, 10 microns or less in size (.000254 inches), can lead to Chronic Beryllium Disease (CBD). CBD is a long-duration, allergic-type lung response that can make the sufferer abnormally weak; it is sometimes fatal. There are no immediate symptoms of CBD and the disease can progress for years without being noticed. When they do occur, the symptoms of CBD include persistent cough, breathing difficulty, chest pain, fatigue and weight loss

Little is known about the pathology of beryllium in the body, why certain people are susceptible to CBD and others are not and how beryllium uptake works at the cellular level.

“We’re looking at a subset of carboxylate groups called acetates, such as acetic acid, a common component of household vinegar and of amino-acids in the body, because they are plentiful and readily bond with metals,” said Brady. “We are searching for a better understanding of what happens in the body when there is uptake of beryllium, and we think these carboxylate groups are a prime site for beryllium to get into a cell.

Brady is using the technologies of Raman spectroscopy, nuclear magnetic resonance and X-ray crystallography to conduct his studies. There are plans for future work with infrared spectroscopy.

Brady’s initial results include the surprising finding that beryllium does not lose it’s solid structure when in solution. It had been theorized that, much like mercury, another metal that is toxic to humans, the structure of beryllium would change in water solution, thus making it more bio-available. ‘This is not the case with beryllium,” said Brady. “The solution and solid structures are about the same; it maintains its form and doesn’t break down under certain conditions.”

“It’s clear that beryllium-cellular transport is not a straightforward process. So we’re hoping that by keeping the molecules simple and using a variety of investigative technologies we can learn the beryllium carboxylate behavior, draw conclusions about beryllium’s behavior in vivo and then supply that data to the biologists who will work to develop protocols that one day could prevent or better treat CBD,” said Brady.

So far Brady has seen specific changes in the spectrum of beryllium in solution under Raman spectroscopy, which he theorizes could lead to better and faster detection methods. “A spin-off of this work could be the development of better detection technologies, which currently consist of swipes and chemical analyses, “ he said.

In the future, Brady hopes to work with more complicated tri-carboxylates and organo-phosphates to understand the functions of the body in relation to beryllium exposure. “We want to take a fundamental look at how beryllium behaves, how it gets to the lungs and how the dose is administered across cell membranes.”

Los Alamos National Laboratory is operated by the University of California for the National Nuclear Security Administration (NNSA) of the U.S. Department of Energy and works in partnership with NNSA's Sandia and Lawrence Livermore national laboratories to support NNSA in its mission.

Los Alamos enhances global security by ensuring safety and confidence in the U.S. nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction and improving the environmental and nuclear materials legacy of the cold war. Los Alamos' capabilities assist the nation in addressing energy, environment, infrastructure and biological security problems.