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March 2005 Issue

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UC Makes 'Significant Breakthrough' in Understanding Heavy Metal Poisoning

Published March 2005

UC researchers have identified the gene responsible for spreading the toxic effects of cadmium--a finding that may one day lead to the prevention of cadmium toxicity in humans.

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 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 appears in the March 1 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 Daniel Nebert, MD, lead author and professor in the Department of Environmental Health and the Center for Environmental Genetics. "We know humans carry the same gene and gene family. Thus, we've identified a target that could be used to prevent cadmium's toxic effects in humans."

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.

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."

Co-authors include Timothy Dalton, PhD, Lei He, Bin Wang, Marian Miller, PhD, Li Jin, PhD, Xiaoqing Chang and C. Stuart Baxter, PhD, all in the Department of Environmental Health, and Keith Stringer, PhD, Department of Pathology and Laboratory Medicine.

The National Institute of Environmental Health Sciences funded the research.

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