McGill University scientists have identified exposure to tungsten as problematic after they determined how and where high levels of the metal accumulate and remain in bone.

Cassidy VanderSchee

“Our research provides further evidence against the long-standing perception that tungsten is inert and non-toxic,” said Cassidy VanderSchee, a PhD student and a member of a McGill research group headed by chemistry professor Scott Bohle.

Tungsten is a hard metal with a high melting point and, when combined with other metals and used as an alloy, it’s also very flexible.

Because of these properties and under the assumption that tungsten is non-toxic, it has been tested for use in medical implants, including arterial stents and hip replacements, in radiation shields to protect tissue during radiation therapy, and in some drugs. Tungsten is found in ammunition as well as in tools used for machining and cutting other metals. 

Tungsten also occurs naturally in groundwater where deposits of the mineral are found. Exposure to high levels of tungsten in drinking water in Fallon, Nevada, was investigated for a possible link with childhood leukemia in the early 2000s. This investigation lead scientists to question the long-held belief that exposure to tungsten is safe and prompted the Centers for Disease Control and Prevention in the U.S. to nominate tungsten for toxicology and carcinogenesis studies.

The McGill scientists exposed laboratory mice to tungsten through drinking water and then examined their bones using the beamlines at the Canadian Light Source. They looked at three parts of the bone: bone marrow, cancellous bone (spongy bone tissue found at the ends of bones), and cortical bone (dense bone tissue found in along the length of bones).

Tungsten was found throughout the bone after mice were exposed to it through drinking water. Image courtesy of Cassidy VanderSchee.

"Tungsten was found in the marrow and cancellous tissue at the end of long bone, with intensities ~ (approximately) 10-fold higher than background levels. These tissues are the site of essential bone functions, such as growth and immune cell formation," reports VanderSchee in her research published in Communications Chemistry.

"Tungsten is also incorporated into cortical bone tissue, which may affect bone structure and integrity."

VanderSchee says she was surprised to learn that once the tungsten accumulates in the bone, it persists even after the source is removed. When the mice were no longer exposed to the tungsten in their drinking water, there wasn’t as much tungsten in their bone marrow and cancellous bone tissue, but there were still high amounts of tungsten in the cortical bone, which doesn’t replace itself as quickly as cancellous bone.

"It is not washing out with time, which is concerning because if somebody is exposed to tungsten and you remove the source of exposure, that person may still have a chronic, low-dose exposure from tungsten remaining in their bone," she said in an interview.

The researchers also looked at the form of tungsten stored in the bone and compared that to the form of tungsten ingested by the mice.

The animals were given simple tungstate, but the tungsten found in the bone resembled a more complicated, reactive form called phosphotungstate. It's believed that the tungsten changed forms in the body as it interacted with the body's normal chemistry.

VanderSchee is continuing her research. Now that she knows the form of tungsten found in the bone, she and the others in the Bohle research group want to learn how and where in the body tungsten is chemically transformed, with the goal of developing drugs that could remove the tungsten from the bone.

“I’m particularly interested in using chemistry to answer biological and health-related questions. We use an inter-disciplinary approach and have a close collaboration with Koren Mann, a McGill immunotoxicologist and Fackson Mwale, an orthopedic researcher also at McGill. We find that using many tools from different disciplines is the best way to approach a complicated health problem like this.”

The scientists conducted some of their research at the National Synchrotron Light Source II at Brookhaven National Laboratory in New York.

VanderSchee, Cassidy R., David Kuter, Alicia M. Bolt, Feng-Chun Lo, Renfei Feng, Juergen Thieme, Yu-chen Karen Chen-Wiegart, Garth Williams, Koren K. Mann, and D. Scott Bohle. "Accumulation of persistent tungsten in bone as in situ generated polytungstate." Communications Chemistry 1, no. 1 (2018): 8. DOI: 10.1038/s42004-017-0007-6

Story by Lana Haight

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