Abstract
Nitrogen-chlorine (NCl) derivatives are a class of long-lived oxidants produced by stimulated phagocytes which may be important mediators of the inflammatory response. Because other phagocyte-generated oxidants cause genetic in cultured chloramine T (ClT), to produce sister-chromatid exchanges (SCEs) in cultured Chinese hamster ovary (CHO) cells. CHO cells were incubated for 30 h with ClT (10 −8 M-10 −5 M) and genetic damage was analyzed utilizing the SCE assay. A significant ( p<0.0005) dose-dependent increase in SCEs was observed. This effect was diminished when cells were treated concomitantly with methionine (10 −5 M), a thioether which reduces NCl back to the parent amine. Extracellularly-generated oxidants must traverse long distances before interacting with nuclear target molecules. Therefore, long-lived NCl derivatives may represent an important class of oxidants which mediate the process of carcinogenesis associated with chronic inflammatory states in vivo.
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