title: In vitro cytotoxicity of various forms of cobalt for rat alveolar macrophages and type II pneumocytes.
abstract: It has been shown that cobalt (Co) and the mixture cobalt-tungsten carbide (CoWC) are cytotoxic for alveolar macrophages (AM) and alveolar type II cells (AT-II), but the exact mechanisms of toxicity are not entirely elucidated. In this study, we exposed primary cultures of AT-II and AM, in vitro, to different forms of Co (Co particles, CoWC particles, CoCl(2)) and assessed cell damage using the dimethylthiazol diphenyl tetrazolium bromide test. In some experiments, inserts were used to separate the particles from the cells. The results show that AT-II are twice as sensitive to the effects of 100 microg Co particles/well (1.88 cm(2)) than AM. For this latter cell type, the presence of WC almost doubled (at 25 microg Co/well) the toxic effects compared to pure Co, but this synergy between Co and WC only occurred if the particles were in close contact with the cells. Lactalbumin and, to a lesser degree, EDTA were able to reduce the toxicity of Co, CoWC, and CoCl(2) for AT-II and AM. CoCl(2) showed a similar toxicity for AT-II and AM. The use of Co-conditioned medium revealed that Co particles are "aged" after having been incubated for 24 h in an aqueous medium and are then no longer able to cause the same degree of cell damage as fresh Co particles (71 versus 15% viability for 100 microg Co/well). The time course of the toxicity of the different forms of Co for AT-II and AM showed different patterns in causing cell damage, suggesting different action mechanisms. Evaluation of cell damage by electron microscopy was consistent with biochemical indices. Overall, our results indicate that the Co ion does play a role in the toxicity of both Co particles and CoWC particles.
authors.affiliation: Laboratory of Pneumology (Unit of Lung Toxicology), K.U.Leuven, Herestraat 49, Leuven, B-3000, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Roesems
authors.forename: P H
authors.initials: PH
authors.lastname: Hoet
authors.forename: D
authors.initials: D
authors.lastname: Dinsdale
authors.forename: M
authors.initials: M
authors.lastname: Demedts
authors.forename: B
authors.initials: B
authors.lastname: Nemery
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004492:Edetic Acid / Q000494:pharmacology; D007768:Lactalbumin / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D013997:Time Factors; D017973:Tungsten Compounds / Q000633:toxicity*
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; D017973:Tungsten Compounds; D003035:Cobalt; D007768:Lactalbumin; D004492:Edetic Acid; C022616:thiazolyl blue; C018021:cobaltous chloride