Current Areas of Research
Evaluation of the Potential Use of Toxicogenomics Technology in Hazard Identification
NTP scientists are working to bring the latest toxicogenomics technology into its testing program to help revolutionize the way NTP conducts its studies. Toxicogenomics examines how the entire genetic structure, or genome, is involved in an organism¿s response to environmental toxicants. It applies gene and protein technologies to environmental medicine by studying the effect of toxicants on gene activity and specific proteins produced by genes. This information could be useful for identifying biomarkers of disease and exposure to toxic substances and for understanding individual genetic susceptibilities.
Preliminary toxicogenomic studies suggest that gene expression often is predictive for phenotypic alterations. The NTP is interested in determining if differential gene expression (DGE) analysis can provide indicators of toxicity at earlier time-points and at lower doses than traditional toxicology parameters. DGE may provide more than a genotypic link to a morphology as it is expected to provide insights into the pathogenesis of the disease and how different rodent models respond to toxic insult.
Perhaps the most exciting potential of toxicogenomics is the possibility to identify biomarkers of exposure or biomarkers of effect. Changes that can be found in readily accessible samples (blood, urine) could then be monitored in clinical studies. When the technology is validated, it will allow repeated sampling of long-term NTP studies to determine whether chemical exposures can be detected or whether developing cancers will provide a genetic signature.
The NTP is currently evaluating study conditions that may contribute to gene expression, e.g., animal and tissue variability, best method of tissue sampling and establishing standards for the conduct of toxicogenomic studies under laboratory conditions. However, a long-term goal of the NTP is to find better and more accurate methods of predicting potential carcinogenicity since current NTP carcinogenicity studies take 4 - 5 years to complete and are costly.
Preliminary toxicogenomic studies suggest that gene expression often is predictive for phenotypic alterations. The NTP is interested in determining if differential gene expression (DGE) analysis can provide indicators of toxicity at earlier time-points and at lower doses than traditional toxicology parameters. DGE may provide more than a genotypic link to a morphology as it is expected to provide insights into the pathogenesis of the disease and how different rodent models respond to toxic insult.
Perhaps the most exciting potential of toxicogenomics is the possibility to identify biomarkers of exposure or biomarkers of effect. Changes that can be found in readily accessible samples (blood, urine) could then be monitored in clinical studies. When the technology is validated, it will allow repeated sampling of long-term NTP studies to determine whether chemical exposures can be detected or whether developing cancers will provide a genetic signature.
The NTP is currently evaluating study conditions that may contribute to gene expression, e.g., animal and tissue variability, best method of tissue sampling and establishing standards for the conduct of toxicogenomic studies under laboratory conditions. However, a long-term goal of the NTP is to find better and more accurate methods of predicting potential carcinogenicity since current NTP carcinogenicity studies take 4 - 5 years to complete and are costly.
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