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THE ROLE OF APOPTOSIS IN NEUROTOXICOLOGY
Citation:
White, L. D., S. E. Hunter, M. W. Miller, M. F. Ehrich, AND S Barone. THE ROLE OF APOPTOSIS IN NEUROTOXICOLOGY. Chapter 5, E. Tiffany-Castiglioni (ed.), Methods in Pharmacology and Toxicology: In Vitro Neurotoxicology: Principles and Challenges. Humana Press Incorporated, Totowa, NJ, , 95-132, (2003).
Description:
Apoptosis, a form of programmed cell death, occurs in the nervous system throughout development, but with a preponderance of cell death occurring during the prenatal and perinatal periods. Aberrant periods of increased or decreased cell death, induced by toxicants in air, water, and food have the potential for producing dysfunctional or nonfunctional neuronal systems in all organisms from single-celled to humans. A number of environmentally-relevant neurotoxicants have been shown to modulate or produce apoptosis through alterations in developmental processes or alterations in cellular and subcellular homeostasis. Organophosphorus pesticides affect apoptosis by targeting mitochondrial function by altering membrane potential and substrate adhesion. Ethanol exposure has been shown to affect apoptosis, as well as proliferation and migration, in developing animals. Heavy metals, including methylmercury, have been implicated in apoptotic cell death in the cerebellum. Exposure to a number of xenobiotics such as hydroxyurea and haloacetic acids results in increased apoptosis during neurulation. This work is aimed at defining apoptosis within a neurotoxicological framework, discussing methodologies for detection/measurement of apoptosis, and illustrating the relevance of measuring apoptosis as an endpoint in determining safety factors and exposure limits for EPA-regulated chemicals.