Published ahead of print on April 8, 2004, doi:10.1165/rcmb.2003-0425OC
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2003-0425OC Respirable Coal Dust Particles Modify Cytochrome P4501A1 (CYP1A1) Expression in Rat Alveolar CellsHealth Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown; and Genetics and Developmental Biology Program, West Virginia University, Morgantown, West Virginia Address correspondence to: Dr. Ann F. Hubbs, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Rd., Morgantown, WV 26505. E-mail: Ahubbs{at}cdc.gov Cytochrome P4501A1 (CYP1A1) metabolizes polycyclic aromatic hydrocarbons in cigarette smoke to DNA-binding reactive intermediates associated with carcinogenesis. Epidemiologic studies indicate that the majority of coal miners are smokers but have a lower risk of lung cancer than other smokers. We hypothesized that coal dust (CD) exposure modifies pulmonary carcinogenesis by altering CYP1A1 induction. Therefore, male Sprague Dawley rats were intratracheally instilled with 2.5, 10, 20, or 40 mg CD/rat or vehicle (saline); and 11 d later, pulmonary CYP1A1 was induced by intraperitoneal injection of ß-naphthoflavone (BNF; 50 mg/kg). Fourteen days after CD exposure, CYP1A1 protein and activity were measured by Western blot and 7-ethoxyresorufin-O-deethylase activity, respectively. CYP1A1 and the alveolar type II markers, cytokeratins 8/18, were localized and quantified in lung sections by dual immunofluorescence with morphometry. The area of CYP1A1 expression in alveolar septa and alveolar type II cells in response to BNF was reduced by exposure to 20 or 40 mg CD compared with BNF alone. CD exposure significantly inhibited BNF-induced 7-ethoxyresorufin-O-deethylase activity in a dose-responsive manner. By Western blot, induction of CYP1A1 protein by BNF was significantly reduced by 40 mg CD compared with BNF alone. These findings indicate that CD decreases BNF-induced CYP1A1 protein expression and activity in the lung.
Abbreviations: aryl hydrocarbon receptor, AhR • alveolar macrophages, AM • aryl hydrocarbon receptor nuclear translocator, Arnt • alveolar type II cells, AT-II • bronchoalveolar lavage, BAL • BAL fluid, BALF • bicinchoninic acid, BCA • ß-naphthoflavone, BNF • coal mine dust, CD • coal workers' pneumoconiosis, CWP • cytochrome P4501A1, CYP1A1 • cytochrome P4502B1, CYP2B1 • enhanced chemiluminescence, ECL • 7-ethoxyresorufin-O-deethylase, EROD • fluorescein isothiocyanate, FITC • immunoglobulin G, IgG • lactate dehydrogenase, LDH • neutral buffered formalin, NBF • proximal alveolar, PA • polycyclic aromatic hydrocarbon, PAH • phosphate-buffered saline, PBS • progressive massive fibrosis, PMF • polymorphonuclear leukocytes, PMN • 7-pentoxyresorufin-O-deethylase, PROD • random alveolar, RA • tris-buffered saline, TBS • xenobiotic responsive element, XRE This article has been cited by other articles:
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