Cytotoxicity is the general quality of being toxic to cells, and can be caused by chemical stimuli, exposure to other cells (NK or T cells for example), or physical/environmental conditions (radiation exposure, temperature or pressure extremes, etc.). Cytotoxic treatment can result in one of three potential cellular fates. Whereas necrotic cell death involves the rapid loss of membrane integrity and cell lysis, apoptotic cell death is slower, more orderly, and is genetically controlled. Cytostasis is a special category of cytotoxicity wherein cells remain alive but fail to grow and divide.
Traditional assays for evaluating cytotoxicity typically probe membrane integrity, looking at the passage of labels into the cell or the leakage of biomolecules out of the cell. One of the major drawbacks of these assays is the fact that they provide only endpoint data. In contrast, xCELLigence real-time cell analysis (RTCA) allows cells to be monitored, in the absence of labels, continuously and automatically throughout the entire course of an experiment. Besides reducing the hands-on time required to run a cytotoxicity assay, the real-time data traces generated by xCELLigence ensure that subtleties of the cytotoxic response aren’t missed.
As described in the Technology Overview, xCELLigence® real time cell analysis (RTCA) interrogates the ability of electrodes in the bottom of E-Plate® wells to conduct electric current. Adhesion of cells to these electrodes impedes electric current, providing exquisite sensitivity to (1) the number of cells present, (2) the size/morphology of the cells, and (3) how tightly the cells are interacting with the plate surface. Cytotoxic responses nearly always involve biochemical changes that directly, or indirectly, affect one or more of the above three parameters. Consequently, xCELLigence is able to monitor cytotoxic responses resulting from an exceptionally wide range of molecular targets (Figure 1).
For specific examples of using xCELLigence to study cytotoxicity, see:
- Cytotoxicity: Compound-Mediated Cytotoxicity
- Cytotoxicity: Irradiation-Induced Cytotoxicity
- Cytotoxicity: Nanotoxicity
For examples of using xCELLigence to study cell-mediated cytotoxicity for cancer immunotherapy, see:
- Cancer Immunotherapy: Antibody-Dependent Cell-Mediated Cytolysis (ADCC)
- Cancer Immunotherapy: Bispecific T Cell Engagers (BiTEs) and Bispecific Antibodies
- Cancer Immunotherapy: Genetically Engineered T Cell-Mediated Cell Killing
- Cancer Immunotherapy: Macrophage-Mediated Phagocytosis
- Cancer Immunotherapy: NK Cell-Mediated Cytolysis
- Cancer Immunotherapy: T Cell-Mediated Cytolysis