For Research Use Only. Not for Use in Diagnostic Procedures.
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.