Toxicity testing, microarray analysis

A number of commercial antibody-based microarrays for multiplexed cytokines analysis are now available (Beckman Coulter BD Biosciences Panom-ics Pierce S S Zyomyx and others). Cytokines are essentially biomarkers of cell injury, inflammation, and apoptosis. They are released by cells in culture in response to drug action (Turtinen et al., 2004) or are elevated in serum in various disease states. Moreover, numerous cytokines are involved in cellular response and many serve as dual effectors (Asao and Fu, 2000). As a result, anticytokine microarrays are being evaluated in drug discovery for off-target toxicity testing to replace standard ELISA plate formats. 

Several projects and consortia were established in order to solve the above-mentioned problems, e.g., the Micro Array Quality Control (MAQC) project, led by US FDA, which main goal is to assess microarray study variability and to develop standards and quality measures for transcriptomics data [50, 51], Another research project, the human embryonic stem cell-derived novel alternative test systems (ESNATS) recently published a paper to address similar questions using human embryonic stem cell-based in vitro test systems for reproductive toxicity by transcriptomics analysis [52], The strong aspect of this study, that it transparently presents difficulties, such as batch effects, and provides analysis strategies including overrepresented transcription factors. It can be used as basis for further development of reproductive toxicity assays based on transcriptomics analysis. 

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