Cytochrome P4501A1 (CYP1A1) induction is suppressed by coal dust exposure in the ovine lung.
Authors
Ghanem-M; Hubbs-AF; Kashon-M; Weissman-D; Porter-D; Batelli-LA; Vallyathan-V; Nath-J
Source
Environ Mol Mutagen 2004 Oct; 44(3):200
Abstract
Cytochrome P4501A1 (CYP1A1) is associated with polycyclic aromatic hydrocarbon-mediated carcinogenesis. We have previously demonstrated suppression of CYP1A1 induction by coal dust (CD) exposure in a rat model. Since it has been controversial whether rat pulmonary responses to particulate parallel those of humans, we questioned whether CD exposure would also alter CYP1A1 induction in a larger species. We instilled the right apical lobes of Katahdin crossbred Iambs with 500 mg CD (<5 microns) or saline using a flexible fiberoptic bronchoscope. 53 or 54 days later, the Iambs received 50 mg/kg IP of the CYP1A1 inducer, betanaphthoflavone (BNF). The Iambs were sacrificed on day 56. The principal histological change in CD-instilled lobes was histiocytic bronchinterstitial pneumonia. CD-instilled lung lobes had increased percentages of bronchoalveolar lavage macrophages and neutrophils and decreased percentages of lymphocytes. CYP1A1-dependent 7-ethoxyresorufin-O-deethylase activity in microsomes prepared from lung tissue was significantly reduced in CD-instilled right lobes relative to uninstilled left lobes or the right lobes of sheep receiving BNF alone. Dual immunofluorescence staining of lung sections for CYP1A1 and the alveolar type 2 (AT-II) cell marker, cytokeratins 8/18, showed that expression of CYP1A1 in whole alveolar septum, AT-II cells and non-type II cells were all significantly reduced by CD exposure. These findings show that in addition to causing pulmonary inflammation, intrapulmonary deposition of CD also modifies induction and cellular localization of CYP1A1 protein in the sheep lung.
Keywords
Dusts; Dust-exposure; Coal-mining; Coal-miners; Coal-dust; Polycyclic-aromatic-hydrocarbons; Carcinogenesis; Carcinogens; Carcinogenicity; Lung-disorders; Laboratory-animals; Animals; Animal-studies; Models; Exposure-levels; Exposure-assessment; Pulmonary-system-disorders; Respiratory-system-disorders
Document Type
Abstract; Conference/Symposia Proceedings
Source Name
Environmental and Molecular Mutagenesis
