The comet assay: A new method to examine heterogeneity associated with solid tumors

DNA strand breaks in individual cells were first measured over a decade ago. The single-cell gel electrophoresis or comet assay, named for the microscopic appearance of the DNA following electrophoresis, continues to evolve and is now being widely adopted by environmental toxicologists and oncologists. It is the first technique that allows measurement of DNA damage in virtually all single cells (including invertebrate or plant cells), and does so rapidly and with a high degree of sensitivity. Figure 1 illustrates the appearance of comets and shows the response of lymphoblast cells to X rays. Initial DNA damage can be detected after exposure of lymphocytes to as little as 5 cGy, equivalent to about 50 single-strand breaks per diploid cell. Although the method has become popular for detecting genotoxic damage in humans and sentinal organisms, the relation between DNA damage and permanent genetic consequences must be determined for each chemical. Probably the most unique and powerful feature of this method is that it can characterize the full range of responses to DNA damage within the individual cells of a heterogeneous population. As many effective anti-tumor treatments produce DNA damage, the comet assay seems ideally suited to characterize tumor heterogeneity, and to predict tumor and normal tissue response to therapy.