DescriptionMicronucleus (MN) formation is a hallmark of genetic toxicity; as such, micronuclei are used as indicators of genotoxicity caused by drug candidates or environmental toxins. The in vitro micronucleus assay is among a new set of genetic toxicology assays wherein cultured cells are treated and scored for micronucleus induction. Existing in vitro assays for micronuclei induction are time-consuming, require multiple trained personnel, can be subjective, and are not automated. Because of these constraints, it has been virtually impossible to test many compounds for this important indicator of genotoxicity. An automated in vitro assay that enables screening for indicators of genetic toxicity earlier in the development of therapeutic candidates would improve attrition rates and yield substantial financial gains for the pharmaceutical industry. We have developed an automated solution with the Thermo Scientific Cellomics Micronucleus BioApplication and HCS Reagent Kit for the ArrayScan HCS Reader. It is a functional assay that measures the frequency of micronuclei (MN) to determine genotoxicity, as well as various indicators of cytotoxicity. The Micronucleus BioApplication enables detection of genotoxicity through examining the frequency of micronucleus formation in single cells (Figure 1). The Micronucleus BioApplication identifies and selects only the desired subpopulation based on analysis of images of fluorescently labeled whole cells and nuclei generated by the ArrayScan HCS Reader. It then detects, distinguishes, and quantitates nuclei and micronuclei in the targeted subpopulation. This BioApplication and Reagent Kit have been optimized for the “cytokinesis-block” method of measuring micronucleus induction. Therefore, in addition to reporting micronucleus frequency as the primary indicator of genotoxicity, it can automatically determine the ratio of multinucleated to mononucleated cells for monitoring cell-cycle delay, an early indicator of cytotoxicity. In addition, the Micronucleus BioApplication reports membrane permeability indicator as a secondary measure of cytotoxicity when used with the Micronucleus HCS Reagent Kit. Various agents can be simultaneously tested for their genotoxicity by comparing micronucleus frequency within the treated population to basal levels of micronucleus formation. The streamlining and automation of this otherwise laborious assay allows the user to test multiple doses of compound at the same time (Figure 2) for a more comprehensive assessment of genotoxic potential, at a substantially lower labor cost than manual methods.
The Micronucleus BioApplication and HCS Reagent Kit provide several advantages over manual methods for genotoxicity evaluation:
- Screen hundreds of compounds a week vs. one compound every few weeks.
- Enable genotoxicity testing to occur earlier in the drug discovery process, saving time and money by eliminating poor drug candidates.
- Detect early and late cytotoxicity for a high-content assay for compound toxicity.
- Provide an answer in days vs. weeks, reducing down-time and increasing efficiency.
The Micronucleus BioApplication decreases the time required to quantitatively analyze populations of cells for micronucleus induction, reduces subjectivity, and provides an easy method for evaluating multiple exposed wells. Whereas manual evaluation of a single compound make take 1-2 weeks, the Micronucleus BioApplication can read results for an entire 96-well plate in less than eight hours. Thus, the Thermo Scientific Cellomics platform provides significant improvements in throughput and cost per compound tested. The BioApplication is therefore essential for screening compounds that are potential genotoxic agents. The BioApplication is designed to work with the reagents and optimized protocol found in the HCS Reagent Kit to provide a cohesive, ready-to-use assay to assess micronucleus formation with your compounds. Features- BioApplication reports the number of nuclei, micronuclei, and percentage of cells that contain micronuclei
- HCS Reagent Kit provides optimized reagents and cell preparation protocol designed to work with the BioApplication
- Automatically distinguishes agents that can lead to micronuclei formation by use of reference wells
- Allows gating of subpopulations of interest using permeability as well as up to three additional channels
- Can simultaneously measure early and late indicators of cytotoxicity by measuring the ratio of multinucleated to mononucleated cells and membrane permeability, respectively
- Flexibility allows optimization of the assay for different cell types including, but not limited to, CHO-K1, BALB-3T3, and V79
Benefits- Significantly reduces time required to evaluate micronucleus formation
- Enables, for the first time, automated screening for genotoxicity
- Provides a more objective analysis of micronucleus formation
- Allows genotoxic compounds to be identified earlier in the drug discovery process, saving valuable time and money
To see validation data using this BioApplication Click here Ordering Information| Buy | Product # | Description | Pkg. Size | | Call to order | S50-0018-1 | Micronucleus Bioapplication | N/A | | Call to order | K11-0001-1 | Micronucleus HCS Reagent Kit | 5 x 96 |
* To order BioApplication Software or Thermo Scientific Cellomics instrumentation, please call 800-432-4091 in the US.
To order Thermo Scientific Cellomics HCS Reagent Kits, please call 800-874-3723 in the US.
To order from elsewhere, contact your local distributor of Thermo Scientific Products. See all Thermo Scientific Cellomics HCS Reagent Kits Download (Coming Soon!): {Instructions} {MSDS} {Certificate of Analysis} Click the link below to view available product brochure
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