Gene expression profile analysis: an emerging approach to investigate mechanisms of genotoxicity.
The response to stress triggers transcriptional activation of genes involved in cell survival and/or cell death. Thus, the monitoring of gene expression levels in large gene sets or whole genomes in response to various agents (toxicogenomics) has been proposed as a tool for investigating mechanisms of toxicity. Although standard in vitro genetic toxicity testing provides relatively simple and accurate hazard detection, interpretation of positive findings, i.e., in vitro chromosome aberrations, in terms of relevant risk to humans is difficult, due to the limited insight into the underlying mechanisms. Therefore, the development of experimental approaches capable of differentiating a wide range of genotoxic mechanisms is expected to significantly improve risk assessment. The goal of this review is to summarize current developments in toxicogenomic analysis of genotoxic stress, and to provide a perspective on the application of gene expression profile analysis in genetic toxicology.
Aubrecht
Jiri
J
Pfizer Global Research and Development, Eastern Point Rd, MS 8274-1246 Groton, CT 06340-8014, USA. jiri.aubrecht @pfizer.com
Caba
Ebru
E
D000818:Animals; D001419:Bacteria / Q000235:genetics; D004249:DNA Damage; D020869:Gene Expression Profiling / Q000639:trends*; D006801:Humans; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D043922:Toxicogenetics / Q000379:methods*
D009153:Mutagens