Accidental and Programmed Cell Death in Investigative and Toxicologic Pathology

Cellular development and homeostasis are regulated via programmed cell death (PCD; apoptosis), which is a genetically regulated cellular process. Accidental cell death (ACD; necrosis) can be triggered by chemical, physical, or mechanical stress. Necrosis is the presence of dead tissues or cells in a living organism regardless of the initiating process and can be observed in infectious and non-infectious diseases and toxicities. This article describes tissue-based immunohistotechnical protocols used for assessing PCD and necrosis in formalin-fixed tissues obtained from preclinical species used in investigative and toxicologic pathology. Two commonly employed protocols for the identification of PCD and necrosis are described in this article: immunohistochemistry (IHC) for cleaved caspase 3, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). TUNEL has been used to detect DNA fragmentation by labeling the terminal ends of nucleic acids in necrotic and apoptotic cells. © 2018 by John Wiley & Sons, Inc.