Toxicology and Radiation Biology

  • Toxicology
  • Biodosimetry
  • Environmental Mutagenesis
  • Mutation Research

Based on the Neon Metafer slide scanning platform, MetaSystems offers an unrivaled portfolio of imaging automation applications for toxicology, radiation biodosimetry, and mutation research. Metafer is the ideal tool for dose-response analyses: it offers extremely fast generation of biodosimetry results, is fully compliant to GLP regulations applied to preclinical genotoxicity studies, is sensitive enough to detect even low dose effects in environmental mutagenicity tests, and is highly flexible and adaptable to any study in mutation research labs.

Aberration Test

Counting dicentric chromosomes and other chromosomal aberrations is generally referred to as the 'Gold Standard' for radiation biodosimetry. Though the assay has been proven to deliver best dose estimates in radiation accidents and in toxicology studies, it is usually time consuming and labor intensive. Metafer1, with its dedicated tools and automated dicentric scoring software, frees the researcher from all tedious and error prone tasks. Additionally, it offers a complete working environment to quickly generate fully documented and reliable results. The Metafer1 platform is compliant to all applicable GLP regulations and to the OECD guideline #473 (In-Vitro Mammalian Chromosome Aberration Test).

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Micronucleus Tests

The cytokinesis-block micronucleus (in-vitro MN) test and the mammalian erythrocyte micronucleus (in-vivo MN) test are both used as tools for fast and precise quantification of DNA damage. Metafer1 offers complete automation for both tests – reliable, fast, and fully documented. Users of the in-vitro MN test receive their results within a few minutes, and each detected bi-nucleate is displayed as a gallery image, together with its micronucleus count. The amounts of mono-, bi-, and multi-nucleates are recorded and may be used to calculate the CBPI index.

Obtaining CBPI in Micronucleus Tests, (87.8kB)

For the in-vivo MN test, Metafer1 automatically assigns each cell to its respective sub-population (PCE or NCE). The assignment is done based on the staining of the cell, and it has the capability to automatically adapt to various staining conditions. Micronuclei are counted in each population, and results are displayed separately as a histogram.

Both tests are GLP compliant and follow the directive of the respective OECD guidelines (#487 for the in-vitro MN test and #474 for the in-vivo MN test). Results may either be summarized in comprehensive and customizable Neon reports, or directly exported to any external statistics software package.

IVMN, (2.2MB)

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Comet Assay

The Comet assay, also known as single cell gel electrophoresis (SCGE) assay, detects DNA damage and repair in individual cells. One major advantage of the Comet assay is the direct assessment of damage on a cell-by-cell basis. The sensitivity of the assay, however, makes it vulnerable to various factors which may affect the reproducibility of results.

Users of MetaSystems devices are able to fully customize the analysis portion of the Comet assay. MetaSystems offers an interactive workstation and an automated slide scanning system based on the Metafer1 platform. Both systems use sophisticated algorithms to obtain head and tail intensities, lengths, and background conditions. They also automatically calculate tail moments and Olive tail moments. The automated system performs the analysis completely unattended, and is capable of distinguishing between ‘normal’ cells and hedgehog comets. Each cell is documented as an image and may also be relocated on the microscope. Data is displayed in useful reports, on-screen graphs, and values that are assigned to gallery images.

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Foci Analysis

Phosphorylated H2AX (also known as γ-H2AX) is a marker for DNA double strand breaks. Fluorescently labeled γ-H2AX protein clusters can be microscopically detected, and thus, can be used as a very direct marker for DNA damage and repair. Metafer1 finds target cell nuclei, acquires signals from multiple focus planes (up to 12 color channels), and automatically analyzes the signals. Co-localization of signals from different channels, analysis of fused signals, and intensity measurements are possible.

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Ames II and Ames MPF Assay

The Ames II / Ames MPF test (based on the method of Xenometrix AG, Basel, Switzerland) is widely used to assess the mutagenic and toxic potential of compounds. The test uses bacteria carrying DNA mutations in genes involved in the synthesis of the amino acid histidine. The Ames II and Ames MPF assays are modernized versions of the original Ames test, using liquid culture instead of agar plates. The assays are done on 384-well microplates and have a colorimetric read-out which may be automatically analyzed by Metafer1. Each single well is interpreted as either positive or negative, giving the user the opportunity to change automatic scores in the event of ambiguous results. Printed results contain color images of each well resulting in a complete overview of the 384 well microplate.

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1 MetaSystems products are used in many countries worldwide. Depending on the regulations of the respective country or region, some products may not be used for clinical diagnostic use. In Europe MetaSystems products are CE labelled in-vitro diagnostics (IVD) devices. In the USA all MetaSystems products except the Ikaros karyotyping systems are intended to be used for research or inspection only.

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