Characterization and Interlaboratory Comparison of a Gene Expression Signature for Differentiating Genotoxic Mechanisms

• DOI: 10.1093/toxsci/kfp103
• Publication Date: 2009-05-23T00:46:43Z
• Authors: Heidrun Ellinger-...; Jennifer M. Fostel; Chinami Aruga; Daniel Bauer; Eric Boitier; Shibing Deng; Donna Dickinson; Anne-Celine Le Fevre; Albert J. Fornace; Olivier Grenet; Yizhong Gu; Jean-Christophe H...; Masako Shiiyama; Roger Smith; Ronald D. Snyder; Catherine Spire; Gotaro Tanaka; Jiri Aubrecht
• Keywords: Toxicogenomics

The genotoxicity testing battery is highly sensitive for detection of chemical carcinogens. However, it features a low specificity and provides only limited mechanistic information required risk assessment positive findings. This especially important in case findings the vitro chromosome damage assays, because may be also induced secondarily to cell death. An increasing body evidence indicates that toxicogenomic analysis cellular stress responses an insight into mechanisms action genotoxicants. To evaluate utility such we evaluated gene expression profiles TK6 cells treated with four model genotoxic agents using targeted high density real-time PCR approach multilaboratory project coordinated by Health Environmental Sciences Institute Committee on Application Genomics Mechanism-based Risk Assessment. We show this profiling technology produced reproducible data across laboratories allowing us conclude relevant set capable distinguishing compounds cause DNA adducts or double strand breaks from those interfere mitotic spindle function as consequence cytotoxicity. Furthermore, our suggest at early time points are most likely provide larger arrays will richer differentiating molecular Although more need tested identify robust signature, study confirms potential investigation mechanisms.