The utility of DNA microarrays for characterizing genotoxicity.
Microarrays provide an unprecedented opportunity for comprehensive concurrent analysis of thousands of genes. The global analysis of the response of genes to a toxic insult (toxicogenomics), as opposed to the historical method of examining a few select genes, provides a more complete picture of toxicologically significant events. Here we examine the utility of microarrays for providing mechanistic insights into the response of cells to DNA damage. Our data indicate that the value of the technology is in its potential to provide mechanistic insight into the mode of action of a genotoxic compound. Array-based expression profiling may be useful for differentiating compounds that interact directly with DNA from those compounds that are genotoxic via a secondary mechanism. As such, genomic microarrays may serve as a valuable alternative methodology that helps discriminate between these two classes of compounds. Key words: biomarkers, gene expression profile, genetic toxicology, mechanism of action, toxicogenomics.
Newton
Ronald K
RK
Division of Toxicology, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, Indiana, USA.
Aardema
Marilyn
M
Aubrecht
Jiri
J
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D018736:DNA Adducts; D004249:DNA Damage; D004785:Environmental Pollutants / Q000506:poisoning*; D020869:Gene Expression Profiling; D006801:Humans; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D043922:Toxicogenetics / Q000639:trends*; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D018736:DNA Adducts; D004785:Environmental Pollutants