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Gene Expression Profiles Rat Out Liver Toxins

NEW YORK (GenomeWeb News) – Gene expression patterns in blood and tissue can reveal information about hidden liver damage caused by drugs and other compounds in rats, new research suggests.
In a paper published online today in Genome Biology, researchers from Clinical Data division Cogenics and the National Institute of Environmental Health Sciences exposed rats to several liver toxins. Using “phenotypic anchoring” — combining gene expression data with traditional toxicological data — the team was able to come up with gene expression signatures from liver tissue and whole blood correlating with the extent of liver damage caused by the toxins.
The researchers gave rats three different doses of eight known hepatotoxins, compounds that lead to liver damage. These doses ranged from sub-toxic to moderately toxic to toxic. For samples taken at each time and dose, the researchers measured gene expression with Agilent and Affymetrix microarrays in combination with more traditional toxicological measures, including phenotype, histopathology, and clinical chemistry.
The team was able to find such gene expression signatures in liver tissue — and, more conveniently, in blood samples that corresponded to histopathology during different stages of liver damage and hinted at the severity of liver damage. Because blood is easier to collect than tissue samples, the gene expression differences in whole blood may have both clinical and research implications.
By looking at the biological functions of these genes, the researchers were also able to learn more about the biology behind toxin-induced liver damage.
And although the researchers faced inter-individual variability that confounded some interpretations, they noted that deciphering this sort of variable sensitivity between individuals could ultimately prove useful since it “provides an opportunity to identify biomarkers that correlate with hyper- and hyposensitivity in individual animals.”
“[T]hese results support the previous findings that toxicants can be classified and differentiated based on gene expression profiling data from the target organ,” the authors wrote, “but extends our understanding by determining that such results can also be obtained using whole blood.”
Beyond the immediate applications for this study, the dataset itself may also become a valuable resource for others doing related environmental and toxicological research, the team said. Data collected for this study is publicly available through the NIEHS web site.

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