TY - CHAP M1 - Book, Section TI - Chapter 3. Mechanisms of Toxicity A1 - Gregus, Zoltán A2 - Klaassen, Curtis D. A2 - Watkins, John B. PY - 2010 T2 - Casarett & Doull's Essentials of Toxicology, 2e AB - Toxicity involves toxicant delivery to its target or targets and interactions with endogenous target molecules that may trigger perturbations in cell function and/or structure or that may initiate repair mechanisms at the molecular, cellular, and/or tissue levels.Biotransformation to harmful products is called toxication or metabolic activation.Biotransformations that eliminate the ultimate toxicant or prevent its formation are called detoxications.Apoptosis, or programmed cell death, is a tightly controlled, organized process whereby individual cells break into small fragments that are phagocytosed by adjacent cells or macrophages without producing an inflammatory response.Sustained elevation of intracellular Ca2+ is harmful because it can result in (1) depletion of energy reserves by inhibiting the ATPase used in oxidative phosphorylation, (2) dysfunction of microfilaments, (3) activation of hydrolytic enzymes, and (4) generation of reactive oxygen and nitrogen species (ROS and RNS).Cell injury progresses toward cell necrosis (death) if molecular repair mechanisms are inefficient or the molecular damage is not readily reversible.Chemical carcinogenesis involves insufficient function of various repair mechanisms, including (1) failure of DNA repair, (2) failure of apoptosis (programmed cell death), and (3) failure to terminate cell proliferation. SN - PB - The McGraw-Hill Companies CY - New York, NY Y2 - 2024/10/12 UR - accesspharmacy.mhmedical.com/content.aspx?aid=6479256 ER -