We are developing a method by which toxicants
can be identified and their putative mechanisms of
action determined by using toxicant-induced gene expression
profiles. In this method, in one or more defined
model systems, dose and time-course parameters
are established for a series of toxicants within a given
prototypic class (e.g., polycyclic aromatic hydrocarbons
(PAHs)). Cells are then treated with these agents
at a fixed toxicity level (as measured by cell survival),
RNA is harvested, and toxicant-induced gene expression
changes are assessed by hybridization to a cDNA
microarray chip (Figure 1). We have developed a custom
DNA chip, called ToxChip v1.0, specifically for
this purpose and will discuss it in more detail below.
The changes in gene expression induced by the test
agents in the model systems are analyzed, and the
common set of changes unique to that class of toxicants,
termed a toxicant signature, is determined.
This signature is derived by ranking across all experiments
the gene-expression data based on rela