title: Cobalt chloride speciation, mechanisms of cytotoxicity on human pulmonary cells, and synergistic toxicity with zinc.
abstract: Cobalt is used in numerous industrial sectors, leading to occupational diseases, particularly by inhalation. Cobalt-associated mechanisms of toxicity are far from being understood and information that could improve knowledge in this area is required. We investigated the impact of a soluble cobalt compound, CoCl(2)·6H(2)O, on the BEAS-2B lung epithelial cell line, as well as its impact on metal homeostasis. Cobalt speciation in different culture media, in particular soluble and precipitated cobalt species, was investigated via theoretical and analytical approaches. The cytotoxic effects of cobalt on the cells were assessed. Upon exposure of BEAS-2B cells to cobalt, intracellular accumulation of cobalt and zinc was demonstrated using direct in situ microchemical analysis based on ion micro-beam techniques and analysis after cell lysis by inductively coupled plasma mass spectrometry (ICP-MS). Microchemical imaging revealed that cobalt was rather homogeneously distributed in the nucleus and in the cytoplasm whereas zinc was more abundant in the nucleus. The modulation of zinc homeostasis led to the evaluation of the effect of combined cobalt and zinc exposure. In this case, a clear synergistic increase in toxicity was observed as well as a substantial increase in zinc content within cells. Western blots performed under the same coexposure conditions revealed a decrease in ZnT1 expression, suggesting that cobalt could inhibit zinc release through the modulation of ZnT1. Overall, this study highlights the potential hazard to lung function, of combined exposure to cobalt and zinc.
authors.affiliation: Laboratoire de développement Analytique Nucléaire, Isotopique et Elémentaire, Gif-sur-Yvette, France. carole.bresson@cea.fr
authors.forename: Carole
authors.initials: C
authors.lastname: Bresson
authors.forename: Carine
authors.initials: C
authors.lastname: Darolles
authors.forename: Asuncion
authors.initials: A
authors.lastname: Carmona
authors.forename: Céline
authors.initials: C
authors.lastname: Gautier
authors.forename: Nicole
authors.initials: N
authors.lastname: Sage
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roudeau
authors.forename: Richard
authors.initials: R
authors.lastname: Ortega
authors.forename: Eric
authors.initials: E
authors.lastname: Ansoborlo
authors.forename: Véronique
authors.initials: V
authors.lastname: Malard
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D003035:Cobalt / Q000145:classification* / Q000378:metabolism / Q000633:toxicity*; D003470:Culture Media; D004357:Drug Synergism; D006706:Homeostasis; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013058:Mass Spectrometry; D015032:Zinc / Q000633:toxicity*
chemical_list: D003470:Culture Media; D003035:Cobalt; C018021:cobaltous chloride; D015032:Zinc