Activation of activator protein-1 by reactive oxygen species associated with asbestos.
Vallyathan-V; Ding-M; Shi-X; Castranova-V
Toxicologist 2000 Mar; 54(1):254
Inhalation of asbestos causes alterations in cell signaling cascades, gene expression, cell injury and cell proliferation which may lead to pulmonary fibrosis, lung cancer, or mesothelioma. Asbestos-mediated free radical reactions are believed to trigger a number of cellular and molecular events that may promote fibrogenesis and carcinogenesis. Because activator protein I (AP-1) plays an important role in pre-neoplastic-to-neoplastic transformation tumor promotion and metastatsis, we studied the possible activation of AP-1 in vitro in cultured JB6 cells and in vivo using transgenic mice after exposure to crocidolite asbestos caused a significant (22-fold) activation of AP-1 in bronchiolar tissue compared to a moderate 10-fold increase in the lung tissue. The induction of AP-1 in asbestos exposure appears to be mediated through the phosphorylation of mitogen-activated protein kinases, Erk 1 and Erk 2. Hydroxyl radical scavengers inhibited asbestos-induced AP-1 activation. These data support the hypothesis that oxygen radical mechanisms may be associated with pulmonary fibrosis and carcinogenesis.
Asbestosis; Asbestos-dust; Inhalation-studies; Pulmonary-system-disorders; Fibrosis; Lung-cancer; Respiratory-system-disorders; Free-radicals; Fibrogenesis; Fibrogenicity; Carcinogenesis; Carcinogenicity; Carcinogens; In-vitro-studies; In-vivo-studies; Laboratory-animals; Animals; Animal-studies
The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania