Scantox offers a range of screening options for assessing a test substance to determine its potential to induce structural chromosomal damage (clastogens) and numerical chromosomal damage (aneugens).
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Such studies are an important component in determining test substances’ overall genotoxic liability, given that chromosomal damage routes can occur when a substance is either DNA reactive (potentially also an Ames test positive) or not directly DNA reactive (potentially Ames test negative). The tools available for screening at Scantox allow the detection of both clastogens and aneugens, using study designs that are high-throughput, quick turnaround, small amounts of test items, and capable of differentiating the toxicological mechanism.
Chromosomal damage is most commonly determined by assessing whether a test substance causes micronuclei formation or by detecting biomarkers in the nucleus, which are precursors to their formation. Most global industries now require the assessment of test substances to determine their ability to induce such chromosomal damage using the OECD 487 in vitro micronucleus test. Increases in micronuclei in the cytoplasm of interphase cells indicate either chromosome breaks (clastogens) or abnormal segregation of chromosomes during mitosis (aneugens). As such, the in vitro micronucleus test can detect both the clastogenic and aneugenic modes of action for a test substance at a single endpoint. Including pan-centromeric FISH probes allows further analysis to assess whether micronuclei are centric (resulting from Aneugens) or acentric (resulting from Clastogens).
Whilst the OECD 487 study is most often conducted using fluorescence microscopy to detect micronucleated cells, this requires a higher test substance amount that is typically available at a screening project stage. Scantox has adapted this method to enable comparable study designs to be performed in a 96-well microplate, analysing cells for micronuclei identical to an OECD 487 study design. This approach is also compatible with FISH, giving a regulatory assessment for as little as 20 mg and capable of screening 100s of test substances across responsive timelines.
Alternative approaches, focussed on higher-throughput and fast-turnaround techniques such as flow cytometry MNT, can also be applied to assess micronucleus formation at Scantox, predicting OECD 487 outcome with low compound usage. This platform can also be applied to MultiFlow®️, which focuses on assessing cellular biomarkers indicating DNA strand breakage, genotoxic stress &/or arrest of cells in mitosis and induction of polyploidy. These markers are used in a statistical toolbox to assess whether test substances will likely present a clastogenic, aneugenic or no genotoxic liability in a screening discovery stage.
These screening options available at Scantox provide a range of options that can be tailored to specific project requirements. They give a comprehensive assessment of chromosomal damage potential at the early screening stage, informing the best next steps, reducing genotoxic liabilities, and promoting project success. Talk to our toxicology team for help with designing the best study package for your needs.