Inhibition of protein synthesis by zinc: comparison between protein synthesis and RNA synthesis

Inhalation of zinc fumes may lead to the acute respiratory distress syndrom e. The mechanisms of pulmonary zinc toxicity are not yet understood. Theref ore we investigated zinc-dependent depression of protein and RNA synthesis in rat and human lung cell lines. 1 After exposure to 120 or 150 mu mol/l zinc, RNA synthesis as assessed by uridine incorporation decreased by 60 - 70% between 0 and 2 h exposition in rat alveolar type II cells (L2 cells) and human fibroblastlike cells (11Lu and 16Lu cells), and by 90% between 0 and 4 h in carcinoma-derived cells ( A549 cells). 2 After 2 h exposure, L2, 11Lu, and 16Lu cells were half-maximally inhibite d by 50 mu mol/l zinc, whereas A549 cells were more resistant with half-max imal inhibition at 100 mu mol/zinc. 3 Protein and RNA synthesis was inhibited in parallel in L2, 11Lu, and A549 cells as indicated by simultaneous determination of uridine and amino acid incorporation. In 16Lu cells, the decline in protein synthesis preceded RN A synthesis inhibition. Pretreatment with RNA synthesis inhibitors (amaniti n or actinomycin D) had no effect on time curve and intensity of RNA synthe sis inhibition. Taken together, our results indicate that the suppression of RNA and protei n synthesis likely are independent phenomena, due to direct zinc effects on these biosynthetic pathways.