Modes of action of toxic agents.

The principal modes of action of toxic agents are discussed in relation to the type of chemical bond formed between the poison and the target constituent of tissues. Alteration of enzyme activity, interference with the binding of poisonous chemicals to proteins, intercalation with nucleic acids, disturbances in electrolyte balance and the disorganization of cellular water and membrane lipids are illustrated as toxic processes involving ionic or van der Waals forces. The reactions of heavy metals with tissue nucleophiles and of exogenous nucleophiles with tissue metals are given brief attention in connection with coordinate-covalent binding. Covalent binding of poisons can arise from the incorporation of an antimetabolite into a larger molecule or reactions of electrophiles or free radicals with tissue constituents. These modes of action are illustrated by chemicals that produce necrosis, allergy or cancer.