Book Chapter Details
Mandatory Fields
Samali A., Zhivotovsky B., Orrenius S.
1999 Unknown
Current Protocols in Toxicology
Current Concepts in Cell Toxicity
John Wiley and Sons, Inc.
New York
Optional Fields
Toxicology, cytotoxicity, cell death, apoptosis, necrosis
Toxicology is sometimes defined as the study of the adverse or harsh effects of toxic agents on living cells, tissues, or whole organisms. The term “toxic agent” is generally used to refer to both naturally occurring toxic substances (toxins) and to harmful products or byproducts (toxicants) generated from human activities, which may have diverse effects on living cells. These agents can be subclassified in various ways—for example, according to their target organ (e.g., liver, kidney, or reproductive organs), industrial use (e.g., food additives or pesticides), source (e.g., animal or plant toxins), and effects (e.g., cancer or liver injury). When a cell is exposed to toxic agents, it will undergo certain molecular or biochemical transformations. The biotransformations or alterations caused by the cell’s exposure to harmful products is generally referred to as cell toxication or cell toxicity. On the other hand, the biotransformations or cellular alterations that lead to the elimination of toxicants or the prevention of toxic metabolite formation from these compounds are called “cell detoxification.” Cell toxicity can have reversible (short-lived or repairable) effects, or affect the cell irreversibly, leading to mutations, malignant transformation, or cell death. The final outcome of being in contact with toxic agents depends mainly on the nature of the toxic substance, the dose applied, and the exposure time. At low doses or short exposure times, small quantities of the toxic agent will come in contact with the cell and be delivered into its cytosol. This may lead to toxicity resulting from the mere presence of the agent in the cell, or the agent may interact with an array of target molecules. Such toxicity initiates a series of events leading to minor and potentially reversible injuries. These events can cause a temporary halt in some of the cellular functions. Similarly, the presence of toxic agents or cellular injuries caused by them may activate the cell’s defenses—detoxification or repair mechanisms—to enable it to withstand such harsh environments and to repair the injuries that have been inflicted upon the cell. The cell’s defense mechanisms involve rapid production or activation of specific molecules—examples of which are heat-shock proteins (HSPs), metallothioneins (MTs), superoxide dismutases (SODs), and catalase— which enable the cell to withstand or tolerate selective toxic agents. A number of xenobiotics (e.g., carbon monoxide, heavy-metal ions, and strong acids and bases) are directly toxic, whereas the toxicity of the others is largely due to production of metabolites. The mechanism of detoxification includes glutathione, cytochrome P-450, Cu, Zn-SOD, and Mn-SOD. However, at high doses or prolonged exposure times, the toxic agents cause irreversible cellular damage, to the extent that the rate of toxication exceeds that of detoxification, leading to a general cellular dysfunction and cell death. This unit attempts to define cell toxicity that leads to cellular demise, with a strong emphasis on cell death via both apoptosis and necrosis, by summarizing some of the more recent developments in cellular, molecular, and biochemical studies of the events that govern the induction and execution of cell death.
DOI: 10.1002/0471140856.tx0201s00
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