One of the major objectives of toxicology is to understand the adverse health effects that result from exposure to foreign chemicals. The traditional method for assessing the toxicity of a test chemical is very resource intensive; requiring the commitment of large amounts of money, time, and animals. According to the National Toxicology Program (NTP), each chemical study requires between 2 and 4 million dollars and several years to complete. Due to the cost and labor intensive nature of these studies, the number of chemicals currently tested by the NTP stands at less than 500. Given these statistics and the fact that there are approximately 70,000 chemicals in commerce today, it is increasingly apparent that alternative methods for assessing toxic potential must be explored if a significant portion of the remaining chemicals is to be tested.
One potential solution is to develop a comprehensive database that describes alterations in gene expression resulting from chemical exposure. The pattern of transcriptional activity will not only be highly sensitive indicator of chemical exposure, but that this pattern will be diagnostic for mechanistically linked toxicants. In our laboratory, we have chosen to address this problem through a combination of high throughput sequencing of expressed sequence tags (ESTs) and construction of custom toxicology-related cDNA microarrays derived from the unique ESTs identifed in the sequencing effort. By using this approach, we can simultaneously develop a quantitative gene expression profile using ESTs and the reagents for further analyzing these changes in a rapid, highly parallel manner. In addition, the expression profiles are not biased for preselected "favorite" genes. The resulting gene expression pattern can then be used as diagnostic fingerprint to predict toxicity and/or carcinogenicity as well as provide valuable insight into the basic biochemical and molecular changes responsible for toxicity.
