Chloramine-induced sister-chromatid exchanges.

Nitrogen-chlorine (N-Cl) 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 damage in cultured mammalian cells, we studied the ability of the synthetic N-Cl compound, chloramine T (Cl-T), to produce sister-chromatid exchanges (SCEs) in cultured Chinese hamster ovary (CHO) cells. CHO cells were incubated for 30 h with Cl-T (10(-8) M-10(-5) M) and genetic damage was analyzed utilizing the SCE assay. A significant (p less than 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 N-Cl back to the parent amine. Extracellularly-generated oxidants must traverse long distances before interacting with nuclear target molecules. Therefore, long-lived N-Cl derivatives may represent an important class of oxidants which mediate the process of carcinogenesis associated with chronic inflammatory states in vivo.