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April 2009 Issue

Iain Cartwright, PhD, and his research team are studying the genetics behind arsenic susceptibility at a time when the issue of arsenic in drinking water has become a worldwide problem. A recent spill of wet coal ash in Tennessee has focused additional attention on the team’s work.
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Environmental Calamity in Tennessee Focuses Attention on Arsenic Research

Published April 2009

When a retaining wall gave way at a Tennessee Valley Authority power plant near Kingston, Tenn., last December, releasing more than a billion gallons of arsenic-laden wet coal ash over 300 acres, it focused attention on an issue that has been a key area of interest for a UC researcher.

Iain Cartwright, PhD, an associate professor in the molecular genetics, biochemistry and microbiology department, and his research team published a paper in the February 2009 issue of Toxicological Sciences that focused on the genetics behind arsenic susceptibility and how individuals could vary in their sensitivity to the toxic effects of environmental arsenic.

Using natural geographic variants as well as genetic manipulation of Drosophila (fruit flies), Cartwright’s team was able to show that altered expression of the glutathione synthetase (GS) gene strongly affects sensitivity to arsenic in both cultured cells and flies.

Glutathione had been known to protect against arsenic toxicity by guarding against oxidative stress and helping to transport arsenic out of the cell.

“We thought in this particular work we would try to let nature tell us something, rather than go and say, ‘Well, I think I’ve got this candidate gene, and that candidate gene, and these could be important.’ Instead, let’s start with a blank slate and say, ‘OK, I don’t know anything about what genes are involved in arsenic tolerance or arsenic susceptibility—let’s just allow nature to tell us, if possible.’

“We have known about the interaction between arsenic and glutathione in cells for many years, but our work using a genetic approach has thrown into focus the particularly critical nature of this interaction,” says Cartwright, adding that the work has produced new insight into the importance of both steps in the glutathione biosynthesis pathway.

Environmental Protection Agency research toxicologist David Thomas, PhD, in a commentary in the same issue of Toxicological Sciences, praised the study’s approach and noted that further research “may help to reduce some of the uncertainties in the risk assessment (for arsenic) and assist regulators in their task of protecting public health.”

Cartwright’s research is gaining attention at a time when the issue of arsenic in drinking water has become a worldwide problem.

According to the World Health Organization, millions of people in Bangladesh are drinking water rich in arsenic. Ironically, while an extensive well-drilling program in recent years has contributed to a significant decrease in diarrheal diseases, it has led to an increase in arsenic exposure from underlying geological strata.

Health risks from long-term exposure to elevated levels of arsenic include skin lesions and several types of cancer, studies have shown. In addition, a study published in 2008 in the Journal of the American Medical Association linked long-term exposure to arsenic with type 2 diabetes.

Following the spill at the Kingston Fossil Plant in Tennessee, state and federal health officials cautioned residents who use private wells or springs to stop drinking the water pending further testing.

Authorities have said municipal water supplies derived from rivers in the area are safe to drink. Cartwright has applied for new National Institutes of Health funding to further his team’s research, which is focusing on the metabolism of heavy metals (such as arsenic and mercury) in the body into organic forms, and the biological pathways disrupted by such species that lead to their carcinogenic activity.

“We’re trying to highlight the biology because there are rarely ‘magic bullets,’” Cartwright adds. “You learn about one pathway and it impinges on a second one, and then a third one. We’re trying to put together the different pieces.”

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