DNA microarrays for detecting endocrine-disrupting compounds

It has recently been discovered that a number of synthetic chemicals and naturally occurring compounds released into the environment can influence endocrine activity. These endocrine-disrupting compounds (EDCs) are highly varied in structure, provenance, and mode of action (MOA). Many EDCs are anthropogenic, products of the chemical industry. Others are natural compounds. Although natural hormones exist at low levels in the environment, industrial sites such as pulp and paper mills and municipal sewage treatment plants can gather large amounts of natural EDCs and release them into the environment as part of their daily operations, thus increasing background environmental concentrations. The potential consequences of endocrine disruption are serious; however, comparatively little is known about the phenomenon. There is considerable debate over the true concentrations, sources, identity, and effects of potential EDCs. Investigation of the problem is hampered by the diversity of potential EDCs, which may have synergistic as well as individual effects, and the complexity of the endocrine system itself Effective and standardized tests to accurately detect the presence of such chemicals in the environment are not available. While many tests have been proposed, they are unsatisfactory because they have only one limited endpoint (e.g., they can detect only one of many potential hormonal responses) and do not provide any mechanistic information. In addition, results from rapid screening tests are difficult to correlate with whole organism response, while larger whole organism bioassays are very costly and time consuming to perform. There is tremendous potential in the application of DNA microarray technology to screen for EDCs. DNA microarrays provide a "snapshot" of transcriptional activity in tissue samples showing which genes were actively expressed within the cells at one point in time. By combining this technology with human cell lines gown in vitro, it should be possible to conduct relatively rapid and straightforward assays to identify EDCs by observing the changes in gene expression patterns in response to exposure. (C) 2003 Elsevier Inc. All rights reserved.