University Of Cincinnati Researchers Discover Gene That Causes Heavy Metal Poisoning

Cadmium--a heavy metal suspected of causing human birth defects, lung cancer and testicular cancer--is found in cigarette smoke, some shellfish and seafood, soil and some plants. It is known to damage the human central nervous system, the kidneys, lungs and developing embryos.

The UC researchers, studying low doses of cadmium in mice, found that the gene Slc39a8 works to transport cadmium to the testes, causing tissue to die.

The study, led by Daniel W. Nebert, MD, professor in UC's Department of Environmental Health and researcher at the Center for Environmental Genetics, will appear in the March 1, 2005 edition of the Proceedings of the National Academy of Sciences (PNAS).

"We suspect that cadmium at higher doses could be transported to other regions of the body via the Slc39a8 gene or another gene in this family," says Dr. Nebert. "We know that humans carry the same gene and gene family. Thus, we have identified a target that could be used to prevent cadmium's toxic effects in human populations."

This is especially important, says Dr. Nebert, for many Third World countries. When populations are malnourished or have iron-deficient anemia, the damaging effects of cadmium increase dramatically.

Humans need certain essential metals--including zinc, calcium, magnesium, iron, copper, cobalt and manganese--for normal metabolism and biological processes.

Industrialization, however, has introduced many nonessential heavy metals, such as cadmium, lead, silver, mercury, nickel, arsenic and chromium into the environment.

In the 1920s, UC researchers determined that exposure to lead (a nonessential heavy metal) in gasoline resulted in birth defects, mental retardation, loss of balance and other brain, kidney, liver or lung damage. Since then, there have been many studies on heavy metal toxicity, but until now no study has determined how nonessential heavy metals cause toxicity in humans or other vertebrates.

"We believe that the Slc39a8 gene could be responsible for the transportation not only of cadmium, but also of other nonessential heavy metals such as lead, nickel and mercury," says Dr. Nebert. "Identification and characterization of this gene in mice is a significant breakthrough that will improve our understanding of how heavy metals actually cause toxicity and cancer in humans."

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Co-authors include Timothy P. Dalton, PhD, Lei He, Bin Wang, Marian L. Miller, PhD, Li Jin, PhD, Xiaoqing Chang and C. Stuart Baxter, PhD, all of UC's Department of Environmental Health, and Keith Stringer, PhD, of UC's Department of Pathology and Laboratory Medicine. The research was funded by the National Institute of Environmental Health Sciences (NIEHS).