Effects of zinc chloride on glutathione and glutathione synthesis rates invarious lung cell lines

Zinc-mediated toxicity has been linked to cellular glutathione (GSH) conten ts. In this study, effects of zinc on cellular GSH content, glutathione red uctase (GR) activity, and GSH synthesis were investigated. In all cell line s tested, decreases in cellular GSH content and GR activity as well as an i ncrease in oxidized glutathione (GSSG) were found after incubation of cells with zinc chloride. These effects were dose- and time-dependent. Changes i n GR activities were earliest affected and were most marked compared with t he other parameters examined. Decrease of enzyme activity was not due to a decrease in the cosubstrate NADPH. In A549 and L2 cells., initial increases in GSH synthesis rates occurred up to about 175% of control. Later, GSH sy nthesis decreased to levels below controls. In 16Lu cells, GSH synthesis de creased after 2 h of zinc exposure. No transient increase was found in this cell line. Measurement of ATP content did not show any influence of zinc o n cellular ATP. Lactate dehyrogenase leakage, a marker of a clear cytotoxic effect, occurred after 6 h of zinc treatment in the non-malignant cells ex amined, and after 16 h in malignant A549 cells. We assume the inhibition of GR activity and the associated increase of GSSG could possibly represent a main zinc-mediated toxic cellular effect.