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"You are what you eat" applies to lab animals

By Laura Stephenson Carter

As researchers toil away in their labs, they carefully control all aspects of an experiment to prevent unexpected variables from tainting their findings. But what if something that never crossed their minds distorts their data?

Diet: A team of DMS researchers—led by graduate student Courtney Kozul and Joshua Hamilton, Ph.D.—discovered just such a factor: the degree to which a lab animal's diet can obscure the results of genetic studies. They set out to explore the effects of two amounts of arsenic—100 parts per billion (ppb) and 10 ppb—on gene expression in mice. But when they learned that a serving of nonpurified lab chow contains as much as 390 ppb of arsenic, they decided to take a close look at lab animals' diets.

Nonpurified chow consists of cereal and assorted sources of protein, including fishmeal, which often contains arsenic and other contaminants. Many animal facilities use such chow because it's cheaper than a purified diet. Researchers may not even know what kind of food their lab animals get, and seldom is the information reported in scientific papers.

Poster: At a national meeting where the research was first presented, "hundreds of people came to my poster almost panicking," says Kozul. They didn't realize lab diets might be skewing their results. The findings have since been published in Chemico-Biological Interactions.

The study, funded by the National Institutes of Health, was conducted with malemice over a period of five weeks. The mice were divided into two groups; one ate regular chow and the other a purified diet with only 20 ppb of arsenic.

The experimental dose of arsenic was administered in the animals' drinking water; some mice in each group got water with 100 ppb of arsenic and some got 10 ppb. Then, using a technique called microarray analysis, Kozul analyzed all 20,000 mouse genes. In the purified diet group, it was clear the 100-ppb dose altered the expression of many genes in the animals' lungs and livers.

But in the regular-chow group, the contaminants "profoundly affect[ed] gene expression," says Hamilton, making it impossible to see the effects of the experimental doses. Of particular concern was the fact that the affected genes are involved in drug metabolism. In previous studies, Hamilton's team—which has always used a purified diet—has shown that arsenic in drinking water disrupts important hormones and contributes to cancer, cardiovascular disease, and diabetes. In 2006, their work led to a lowering of the federal limit for arsenic in drinking water—from 50 ppb to 10 ppb.

The study showed that "diet has profound effects on how our body responds," says Hamilton. He has since left Dartmouth to be chief academic and scientific officer at the Marine Biological Laboratory in Woods Hole, Mass., but Kozul is continuing her research at DMS. Her latest finding was that arsenic affects genes that control the immune response of lung cells.

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