41] Cytotoxicity of chloramines

Abstract

This chapter describes the cytotoxicity of chloramines. The binding of ligands to the membrane-surface receptors of neutrophilic leukocytes stimulates the reduction of oxygen (O2) to superoxide (O2–) and the secretion of cytoplasmic granule components including myeloperoxidase into the intracellular phagolysosome compartment and the extracellular medium. When neutrophils are incubated with target cells, nitrogen–chlorine (N–Cl) derivatives react with both types of cells so that results are influenced by the neutrophil:target cell ratio and the reactivity of N–Cl derivatives toward neutrophil and target cell components. Methods for evaluating the cytotoxicity of N–Cl derivatives consist of measuring oxidation, chlorination, or other chemical modifications of cell components and measuring lysis or the failure of specific structural or functional components of cells. Stimulated neutrophils undergo a progressive myeloperoxidase-dependent inhibition of O2 and glucose metabolism. This inhibition results from the reaction of hypochlorous acid (HOCl) with ammonium (NH4+) produced by the cells. Monochloramine (NH2Cl) is produced as a result and inactivates neutrophil components.