[Gene expression and environmental exposure to xenobiotics: overview and applications]

Industrial chemicals, pesticides, pharmaceuticals, foods, heavy metals, air pollutants, and naturally occurring substances, are an integral part of our daily lives. Environmental exposure can induce changes in gene regulation associated with human diseases. A new discipline of toxicology is "predictive toxicology" that defines the relationship between the structure and activity of the genome and the adverse biological effects of exogenous agents. Toxicogenomic technologies allow complete assessment of the functional activity of biochemical pathways, and of the structural genetic (sequence) differences among individuals (polymorphisms), that were previously unattainable. Microarray technology provides the means to study multiple pathways and mechanisms at concurrent times. Gene expression is a sensitive indicator of toxicant exposure, disease state, and cellular metabolism and thus represents a way of characterising how cells and organisms adapt to changes in the external environment. The application of these technologies to toxicology can lead us into a new era when genotypes and toxicant-induced genome expression, proteins, and metabolite patterns can be used to screen compounds for hazard identification, to monitor individual exposure to toxicants, to track cellular responses to different doses, to assess mechanisms of action, and to predict individual variability in sensitivity to toxicants and potential ways to improve risk assessment.