Cell signaling pathways elicited by asbestos.
Mossman-BT; Faux-S; Janssen-Y; Jimenez-LA; Timblin-C; Zanella-C; Goldberg-J; Walsh-E; Barchowsky-A; Driscoll-K
Environ Health Perspect 1997 Sep; 105(Suppl 5):1121-1125
The induction of multiple signaling pathways by exposure to asbestos (1332214) fibers was investigated in hamster tracheal epithelial (HTE) cells. A diploid line of HTE cells was incubated with crocidolite (12001284) at 1.25 or 5.0 micrograms/square centimeter of culture dish. At 2 to 24 hours after crocidolite addition, cells were isolated for preparation of nuclear extracts for electrophoretic mobility shift assays. Evidence indicated that crocidolite asbestos causes nuclear factor kappa-B activation in HTE cells. The activation of the extracellular signaling kinase/mitogen activated protein kinase (MAPK) cascade by crocidolite asbestos after phosphorylation of the epidermal growth factor receptor was considered. The cell signaling events, particularly the balance between ERK and stress related protein kinase activities in the MAPK pathway may be important in induction of cell proliferation or apoptosis with phenotypic end points occurring in pulmonary epithelial and pleural mesothelial cells after exposure to asbestos. The authors conclude that multiple cell signaling pathways may be stimulated by mineral dusts. Probable mediators in these pathways are oxidants that phosphorylate either receptors on the cell surface or other signaling proteins occurring upstream of transcription factor interaction with DNA. Active oxygen species may also be important in the degradation of proteins in these cascades or in the initiation of lipid peroxidation cell signaling pathways yet to be characterized after exposure of cells to minerals.
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Cytotoxic-effects; Cell-damage; Asbestos-fibers; Mammalian-cells; Mineral-dusts; In-vitro-studies; Respiratory-system-disorders; DNA-damage
Pathology University of Vermont Medical Alumni Bldg Burlington, VT 05405
Environmental Health Perspectives
University of Vermont & St Agric College, Burlington, Vermont