Environmental and Molecular Mutagenesis (EMM) Editor's Choice - December 2014
The Editor's Choice for December is "Validation of a High Throughput Flow Cytometric In Vitro Micronucleus Assay Including Assessment of Metabolic Activation in TK6 Cells” by Annemette V. Thougaard, Joan Christiansen, Tomas Mow, and Jorrit J. Hornberg.
In their Editor’s Choice article, Thougaard et al. describe the most comprehensive validation study of the high throughput flow cytometric MN assay ever conducted. The authors assessed the MN induction of 64 compounds selected to include in vivo genotoxicants, nongenotoxic chemicals, and drugs. The MN assay was conducted in a 96-well format both with and without metabolic activation. They established relevant cut-off values to classify a compound as genotoxic (fold MN increase of 4.5) and exclude interference due to cytotoxicity (fold ethidium monoazide positive cell increase of 3.5, in addition to using the recommended relative nuclei count value of <0.45). Thereby, they avoided irrelevant positives and, consequently obtained an optimal balance of high sensitivity (88%) and high specificity (87%) in the characterization of genotoxicants. Overall, this article provides important recommendations and perspectives regarding the MN assay for investigators in the fields of early drug discovery and regulatory safety assessment. By deselecting genotoxic compounds early from the drug discovery process, the number of animal experiments may also be reduced. Environ. Mol. Mutagen. 55: 704-718. © 2014 Wiley Periodicals, Inc.