Aneugen Versus Clastogen Evaluation and Oxidative Stress-Related Mode-of-Action Assessment of Genotoxic Compounds Using the ToxTracker Reporter Assay.

摘要: Understanding the mode-of-action (MOA) of genotoxic compounds and differentiating between direct DNA interaction indirect genotoxicity is crucial for their reliable safety assessment. ToxTracker a stem cell-based reporter assay that detects activation various cellular responses are associated with cancer. consists 6 different GFP cell lines can detect induction damage, oxidative stress, protein damage in single test. The thereby provide insight into MOA compounds. Genotoxicity detected by 2 independent reporters. Activation Bscl2-GFP adducts subsequent inhibition replication Rtkn-GFP activated following formation double-strand breaks. Here, we show differential these reporters could be used to further differentiate reactive clastogenic or non-DNA-reactive aneugenic For classification compounds, was extended cycle analysis aneuploidy extension validated using selection 16 (genotoxic) well-established MOA. Furthermore, related production oxygen species investigated stress combination scavengers. With new extensions, able accurately classify as nongenotoxic discriminate DNA-reactive aneugens, caused stress.