In vitro alveolar cytotoxicity of soluble components of airborne particulate matter: effects of serum on toxicity of transition metals

Respiration of fossil fuel-derived airborne particulate matter (PM) has been linked to various pulmonary disorders. Transition metals contained in such PM, such as zinc, iron and vanadium, have been suggested as the primary culprits in PM-induced pulmonary distress by rat instillation studies. In this study, the cytotoxicity of zinc, iron, and vanadium on confluent monolayers of rat alveolar epithelial cells was evaluated as the inhibition of cellular succinate dehydrogenase metabolic activity as quantified via the MTT assay. In addition, the effect of culture medium serum concentration on the toxicities of these three metals was investigated. Of the three metals tested, zinc was the most toxic, with an EC50 of 0.6 mM in culture medium with 10% serum; vanadium and iron had EC50's of 3 and 4 mM respectively. Serum in culture medium was found to substantially reduce the apparent toxicity of zinc: EC50's for zinc ranged from 0.6 mM in 10% serum to 0.1 mM in serum-free medium. Zinc toxicity analyses in various culture medium conditions demonstrated that the toxicity-reducing effect of serum was due largely and perhaps entirely, to serum albumin. Some, but not all of the effect of serum and albumin on zinc toxicity is apparently due to zinc-albumin binding. (C) 2004 Elsevier Ltd. All rights reserved.