The ability to measure early indicators of toxicity is an essential part of drug discovery. In vitro cytotoxicity assays involving tissue specific cell cultures are considered as valuable predictors of human drug toxicity. As a primary organ for drug metabolism, the liver is often subject to toxic effects, so in vitro cellular cytotoxicity studies focus on human hepatocytes.
Early and late indicators of in vitro cytotoxicity include plasma membrane integrity, mitochondrial mass and mitochondrial membrane potential, cell number, caspase activation, nuclear swelling and shrinking and DNA fragmentation.
Determining the count of a cell population is a very sensitive indicator of cell stress since cell proliferation requires intact cell structures and function.
Cytotoxicity assays and their desired readout parameters can vary largely, depending on target cells and compound type. Adaptation of the assay with respect to reagent used, parameters to be evaluated, end point, live or fixed cells and number of cells per sample is critical.
The figure above shows a schematic representation of mitochondrial mass (in this case increasing) and nuclear area changes (in this case decreasing) upon cytotoxic treatment. The cells have been stained with a mitochondrial marker (red) and a nuclear stain (green) in various stages after treatment with a cytotoxic compound. From left to right: increasing dose of compound.
Our Cytotoxicity solutions
Drawing on many years of experience and in-depth knowledge, PerkinElmer offers solutions for every throughput, a starting point for typical cytotoxicity assays and unlimited possibilities for customization:Opera
High Content Screening System
- High sample throughput with multi-color parallel image acquisition and over 100,000 data points per day
Image Analysis Software
- Unlimited possibilities for adding parameters and modifying readout
- Image analysis sequences for e. g. transition of G2 to M-phase (cyclin B1 staining), mitotic index (phosphohistone H3), S-Phase quantification (BrdU, EdU staining), DNA content
Compact High Content Screening System
- High speed with large field of view and large cell number captured with every image
- Ready to use protocols with reagent recommendations, ready- made image analysis sequences and documentation on how to customize
High Volume Data Management and Analysis System
- Enterprise level data management from assay development to high throughput screening seamlessly linking high content data, research data, in vivo imaging data, result management, screening statistics, biological and chemical data
Automated High Content Screening System
- Full environmental control and workstation with hand-over of plates from imager to incubator for short-term and long-term live cell assays
You may also be interested in: Live Cell Imaging.