Respirable Coal Dust Particles Modify Cytochrome P4501A1 (CYP1A1) Expression in Rat Alveolar Cells
| Autor: | Mark Barger, Lori A. Battelli, Michael L. Kashon, Joginder Nath, Mohamed Ghanem, J. Y. C. Ma, Vincent Castranova, Ann F. Hubbs, Dale W. Porter, Val Vallyathan |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.medical_treatment Blotting Western Clinical Biochemistry Intraperitoneal injection Fluorescent Antibody Technique Immunofluorescence medicine.disease_cause Rats Sprague-Dawley Alveolar cells Western blot Macrophages Alveolar Cytochrome P-450 CYP1A1 polycyclic compounds medicine Animals heterocyclic compounds Lung cancer Lung Molecular Biology medicine.diagnostic_test Chemistry Dust Cell Biology respiratory system medicine.disease Molecular biology Rats Blot Coal medicine.anatomical_structure Carcinogenesis |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 31:171-183 |
| ISSN: | 1535-4989 1044-1549 |
| Popis: | 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 beta-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. |
| Databáze: | OpenAIRE |
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