Enhancement of Chemical Activation via Radical-Dependent Mechanisms: An Emerging Concept in Chemical-Chemical Interactions
The biological effects of exogenous chemicals including drugs, are initiated through physiochemical interactions between the chemical and specific tissue macromolecules, such as enzymes, structural and receptor proteins, and nucleic acids. In most cases, such interactions provide the molecular basis for both the pharmacologic and toxic effects of xenobiotics. One of the possible results of the interaction of a chemical with cellular enzymes is its metabolism to a bioreactive intermediate.1 The reaction of either this initial reactive metabolite or a secondary reactive product with critical target molecules can then bring about changes in cellular function. Reactions which result in the enhanced activation of a chemical can then result in an increased pharmacologic or toxicologic effect. Chemical-mediated induction of enzymes involved in the metabolism of xenobiotics is a well-established mechanism whereby a chemical can indirectly enhance the activation and hence the potential toxic actions of another chemical2.
KeywordsMouse Lung Covalent Binding Butylate Hydroxy Toluene Pulmonary Toxicity Phenoxy Radical
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