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The mechanisms of toxic tissue injury and cell death underlie numerous human diseases as well as the effects of pharmaceutical drugs and environmental toxins. These mechanisms are complex and vary with tissue structure, vascularization, spectrum of cell death proteins, nature of damaging agent, the strength, length and frequency of the exposure to the injury, and many other factors. Accordingly, cell death can take forms of apoptosis, necrosis, autophagy, mitotic catastrophe, as well as some intermediate or more specific forms of cell death including aponecrosis, oncosis, anoikis or abortosis. To approach this complexity, the best strategy for assessment of toxic tissue injury includes the use of: a) common methods that occur in all injuries independent of causes, mechanisms or the origin of tissue; b) methods that are quantitative; and c) approaches that allow, if necessary, combining observations with other methods to determine the mechanism of cell injury and death.

DNA fragmentation (i.e., accumulation of unprepared double-stranded DNA breaks) is a form of DNA damage, which indicates that cell death reached the point of no return and became irreversible. DNA fragmentation is a hallmark of all types of cell death regardless of the mechanism. To determine the mechanisms and molecules involved in cell death, DNA fragmentation assays can be easily combined with immunocytochemistry.