DNA microarrays and toxicogenomics: Applications for ecotoxicology?
Abstract
Toxicogenomics attempts to define how the regulation and expression of genes mediate the toxicological effects associated with exposure to a chemical. DNA microarrays are rapidly becoming one of the tools of choice for large-scale toxicogenomic studies. An approach in modern toxicogenomics has been to classify toxicity based on gene transcriptional patterns; comparing the transcriptional responses of a chemical with unknown toxicity to those for which the transcriptional profiles and toxicological endpoints have been well characterized. Recent evidence suggests that gene expression microarrays may be instrumental in defining mechanisms of action of toxicants. However, several assumptions are inherent to a toxicogenomic-based approach in toxicology, many of which remain to be validated. Gene expression profiling using DNA microarrays represents a snapshot of the gene transcriptional responses occurring at a particular time and within a particular tissue. Toxicity, on the other hand, represents a continuum of possible effects governed by both temporal and spatial factors that are inextricably contingent upon the exposure conditions. The perceived toxicological properties of any chemical are dependent on the route, dose, and duration of the exposure, and as such, gene expression patterns are also subject to these variables. Correct interpretation of DNA microarray data for the assessment of the toxicological properties of chemicals will require that temporal and spatial gene expression profiles be accounted for. These considerations are further compounded in ecotoxicological studies, during which altered gene expression patterns induced from exposure to an anthropogenic substance must be discernible over and above the complex effects that phenotypic, genotypic, and environmental variables have on gene expression. To this end, the greatest utility of DNA microarrays in the field of ecotoxicology may be in predicting the toxicological modes of action of anthropogenic substances on host physiology, particularly in non-model organisms. Predictable and accurate assessment of the impacts of a chemical substance in ecotoxicology will require that classical toxicological endpoints be used to validate any effects predicted based on gene expression profiling. Validated expression profiling may subsequently find utility in ecotoxicological-based computer simulation models, such as the Biotic Ligand Model (BLM), in which gene expression information may be integrated with geochemical, pharmacokinetic, and physiological data to accurately assess and predict toxicity of metals to aquatic organisms. © 2002 Elsevier Science Inc. All rights reserved.