Project name: Homo sapiens

Description: Due to its high throughput nature, toxicogenomics can provide a broad picture of a toxic response, offering the ideal functional platform for grouping chemicals according to mechanistic similarity. In this way, toxicogenomics has found its way into predictive toxicology. However, so far, the predictive potential of toxicogenomics in an endocrine disruptive screening context has not been extensively examined. The aim of this study was to combine a toxicogenomics approach with an estrogen-sensitive MCF-7 cell system. In total, 18 compounds with endocrine disruptive potential were selected, of which 11 are listed as ICCVAM reference compounds for validation of estrogen receptor (ER) binding and transactivation assays. In this way, the grouping and classification potential of the gene expression profiles could be directly compared to the more classical estrogenicity screens, such as ER binding, ER transactivation and MCF-7 cell proliferation assays. Results indicated that this toxicogenomics approach was clearly capable of grouping compounds into strong, weak and non estrogenic groups. This demonstrates the value of toxicogenomics for evaluating gradual differences in related modes of action, in addition to the more common search for opposite modes of action. The chemical groups were represented by interesting marker genes such as PGR, ERBB2, CXCL12, AREG and EGR3, including some early-responsive (4h) potential biomarkers. These results open the discussion on the added value of a broader endpoint evaluation in estrogenicity screens provided by omics-techniques compared to the classical single endpoint based assays.Overall design: The samples are hybridized in 12 loop designs that can be connected in the analysis via a reference sample that all loop designs have in common.The 11 ICCVAM reference compounds are: 17beta-estradiol, 2,3,7,8 Tetrachloro-dibenzo-p-dioxin, Atrazine, Genistein, Nonylphenol, Kepone, Testosterone, Methoxychlor, Lindane, p,p'-DDT, Diethylhexylphthalate.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2009-06-29