Gene expression, dose-response, and phenotypic anchoring: applications for toxicogenomics in risk assessment.

There are a number of ways in which global analysis of gene expression may be useful in improving the way we assess the risk of chemical agents, especially at the concentrations to which people are likely to be exposed. The methodology for assessing changes in gene expression is quite sensitive: most of the methods in use today have attomolar or even sub-attomolar sensitivity. That sensitivity, coupled with the observation that virtually all toxic responses are accompanied by changes in gene expression, suggests that it is possible to use gene expression analysis to determine whether responses at the molecular level continue to occur at dose levels below those that produce frankly adverse effects. This kind of information will be extremely important in addressing controversies about the likelihood of occurrence of those adverse effects at ambient exposure levels.