ABSTRACT
The field of developmental toxicology, like virtually every other life science discipline, is being revolutionized by the advent of genomic tools that allow the investigation of changes in every gene in a biological sample simultaneously. We have long understood that adverse responses to exogenous perturbations, although manifested as changes at the structural or organ level, are attributable to changes that occur at more fundamental levels of biological organization: tissues, cells, and genes. This concept has been at the core of the reductionist, mechanistic approaches to studying abnormal development that have contributed so much to the field over the last four decades. From this research, we have learned that abnormal development can be caused by a number of mechanisms, only some of which are directly attributable to changes in the expression of genes. However, as genomics experiments become more commonplace in toxicology, it is becoming clear that, irrespective of ultimate mechanism, the pathogenesis of virtually all toxic responses involves some change in gene expression (1, 2). The fact that gene expression changes are so universal to toxicity suggests that global analysis of gene expression may be an important tool in understanding toxic mechanisms, predicting toxic response, extrapolating across experimental models and to humans, and addressing many other questions that are important in basic and applied toxicology and risk assessment.
