RT Book, Section A1 Lehman-McKeeman, Lois D. A2 Klaassen, Curtis D. A2 Watkins, John B. SR Print(0) ID 1178013063 T1 Mechanisms of Toxicity T2 Casarett & Doull’s Essentials of Toxicology, 4e YR 2021 FD 2021 PB McGraw Hill PP New York, NY SN 9781260452297 LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1178013063 RD 2024/10/05 AB KEY POINTSToxicity 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.