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SAN FRANCISCO--Scientists dream of someday using a simple chip studded with DNA to help determine the health risk of drugs, food additives, or industrial chemicals. Now, that technique has passed a preliminary test with flying colors, researchers reported here on 26 March at a meeting of the Society for Toxicology.
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Active genes. Microarrays, which can detect the activity of thousands of genes at once, may help predict the toxicity of chemical compounds.
CREDIT: INCYTE PHARMACEUTICALS |
The principle is simple. Researchers expose lab animals to a chemical, then extract genetic material called mRNA (which is produced only by active genes) from their cells. A so-called microarray or DNA chip tests for the activity of thousands of genes at once. The profile of active genes should reveal exactly what the toxin does to the animal--if the signal can be distinguished from normal changes in gene activity.
A few months ago, Cynthia Afshari of the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, put the new technology to the test. Using microarrays of 1700 genes likely to be important in rats' response to toxins, Ashfari's team first produced genomic fingerprints for two types of well-studied liver toxins: phenobarbital and three members of a chemically diverse class of compounds called peroxisome proliferators. Then they did a blind test of rat mRNA from another lab.
By comparing gene activity for these 26 extracts to the two references, Ashfari's postdoc Hisham Hamadeh correctly identified all the rats that had been exposed to a peroxisome proliferator or a derivative of phenobarbital. He also recognized that several rats had been exposed to a wild-card compound not in the database. Hamadeh made only one error, misidentifying one wild-card sample as a weak analog of phenobarbital; it was actually an unrelated compound.
The accuracy of the DNA array amazed scientists who packed the room for Afshari's presentation. "This is important work," says J. Christopher Corton, of the CIIT Centers for Health Research in Research Triangle Park, North Carolina. Toxicologists still have a long way to go before they can use genomic tests to predict a wide range of toxicities, he adds. But Afshari's work shows that the goal may be reached a lot more quickly than expected, Corton says.
--RICK LOVETT
Related sites
Abstract of the talk
Cynthia Afshari's home page
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