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Researchers Use SELDI to Find Biomarkers That Could Help Determine Lead, Arsenic Exposure


Using SELDI technology, researchers at the Guangxi Institute of Occupational Health in China and the Harvard School of Public Health in Boston have identified a panel of five biomarkers that may help determine concurrent exposure to lead and arsenic.

"Proteomics is a new, emerging technique. … We know this technique is sensitive and powerful, so we tried to use it in this field to see if we can find something useful or meaningful for occupational health problems," said Rihong Zhai, the first author of the lead and arsenic study who is a research fellow at the Harvard School of Public Health.

The study, published in the December 2005 issue of Biometals, is one of a growing number of studies that use proteomic techniques to find biomarkers that can indicate exposure to environmental contaminants. Another study by researchers at the University of California, Berkeley, published in November 2005, identified two proteins that could potentially serve as markers for a benzene-exposure test (see ProteoMonitor 12/2/2005).

Currently, concentrations of lead in blood are measured directly to determine lead exposure, and arsenic concentrations are measured in urine to determine exposure. However, there are no biomarkers to represent exposure to a mixture of lead and arsenic, which may have combinatorial effects, Zhai said.

"In real life, people are usually exposed to a mixture [of lead and arsenic], and we didn't have any biomarker that could be used as a marker of mixture exposure," said Zhai. "The proteomic biomarkers we found are markers of mixture exposure."

"We know [proteomics] is sensitive and powerful, so we tried to use it in this field to see if we can find something useful or meaningful for occupational health problems."

It is known that exposure to lead can lead to cancer and kidney, nervous system, immune system, and reproductive damage, while arsenic exposure can lead to lung cancer and skin cancer. However, the effects of combined exposure to lead and arsenic have only been studied in vitro, Zhai said.

Accordint to Zhai, in vitro studies showed that cell cultures exposed to both lead and arsenic suffered more cell death and oxidative damage to DNA than cell cultures exposed to either lead or arsenic alone.

Aside from serving as a combinatorial biomarker, another advantage of the protein biomarker panel may be that it is more sensitive in detecting exposure to lead and arsenic than current blood and urine tests.

To find their panel of five biomarkers, Zhai and his colleagues studied the proteins in blood of 46 males who worked in a smelter in the Guanzhou province of southern China. Those workers were exposed to both lead and arsenic, according to air quality measurements.

As controls, the researchers studied 45 age-matched males who worked in an office nearby where there was no lead or arsenic in the air.

Using SELDI, the researchers compared the proteomes of blood samples from exposed workers and non-exposed controls. The five proteins/peptides that they found could discriminate between exposed and non-exposed workers had masses of 2,097 daltons, 2,953 Da, 3,941 Da, 5,338 Da, and 5,639 Da. The proteins were not sequenced or identified.

When compared with the "gold standard" blood and urine tests, the panel of five biomarkers had a sensitivity of 87 percent and a specificity of 89 percent in distinguishing exposed workers from non-exposed workers.

Zhai said that the next step is to isolate the five protein biomarkers from serum, to sequence the proteins, and to identify them. After that is done, the researchers will try to test the biological functions of the proteins.

"We know a lot about the health effects of exposure to individual lead, or individual arsenic, but little is known about the combined effect of mixture exposure," said Zhai. "Hopefully, if we can test the biological functions of these markers, we can learn more about the effects of exposure."

After the markers are identified and characterized, the researchers would like to conduct a larger validation study to test how effective the biomarker panel is at determining exposure to lead and arsenic.

"Right now we are just at the beginning of this kind of study," said Zhai. "We still have many, many things to learn and to do."

If the lead and arsenic studies are successful, the researchers may use the same techniques to study other types of environmental exposures as well, Zhai said.

The best prevention for lead and arsenic exposure is to maintain equipment so that the metals do not get in the air, and to wear a mask to help prevent breathing in the contaminants, Zhai said.

For the smelter workers in the study who were found to have high levels of lead and arsenic in their blood and urine, medical treatment was given at a local hospital. The treatment moves lead and arsenic out of the body.

— Tien-Shun Lee ([email protected])

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