Use of cDNA microarrays to probe and understand the toxicological consequences of altered gene expression.

Genomic sciences offer the ability to measure quantitative modulation of transcription in cells and tissues under a wide variety of conditions. We have developed a series of custom cDNA microarrays specifically to investigate toxicity processes. Around 600 marker genes for toxicity were selected and representative cDNA clones were obtained, amplified and purified by polymerase chain reaction (PCR), before being immobilised on nylon membranes. A detailed database on biochemical function, role in disease and allelic variation has been assembled for each gene. Applications in our laboratory include mechanistic investigation of a number of toxic endpoints such as hepatotoxicity and endocrine disruption.