Expression of Xenobiotic Metabolizing Enzymes in Different Lung Compartments of Smokers and Nonsmokers

• Published in: Environmental health perspectives 2006-11, Vol.114 (11), p.1655-1661
• Main Authors: Thum, Thomas, Erpenbeck, Veit J, Moeller, Julia, Hohlfeld, Jens M, Krug, Norbert, Borlak, Jürgen
• Format: Article
• Language: English
• Subjects: Adult; Air forces; Body mass index; Bronchi - metabolism; Bronchoalveolar Lavage Fluid - chemistry; Chemical hazards; Constitutive Androstane Receptor; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Dioxins; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enzymes; Female; Gene expression; Gene Expression Regulation; Genetic aspects; Humans; Liver X Receptors; Male; Middle Aged; Orphan Nuclear Receptors; Oxygenases - genetics; Oxygenases - metabolism; P values; Phthalates; Pregnane X Receptor; Prostatic diseases; Prostatic hyperplasia; Ranches; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - metabolism; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Receptors, Steroid - genetics; Receptors, Steroid - metabolism; Smokers; Smoking; Smoking - adverse effects; Smoking - metabolism; Testosterone; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.8861

Background: Cytochrome P450 monooxygenases (CYP) play an important role in the defense against inhaled toxicants, and expression of CYP enzymes may differ among various lung cells and tissue compartments. Methods: We studied the effects of tobacco smoke in volunteers and investigated gene expression of 19 CYPs and 3 flavin-containing monooxygenases, as well as isoforms of gluthathione S-transferases (GST) and uridine diphosphate glucuronosyltransferases (UGT) and the microsomal epoxide hydrolase (EPHX1) in bronchoalveolar lavage cells and bronchial biopsies derived from smokers (n = 8) and nonsmokers (n = 10). We also investigated gene expression of nuclear transcription factors known to be involved in the regulation of xenobiotic metabolism enzymes. Results: Gene expression of CYP1A1, CYP1B1, CYP2S1, GSTP1, and EPHXI was induced in bronchoalveolar lavage cells of smokers, whereas expression of CYP2B6/7, CYP3A5, and UGT2A1 was repressed. In bronchial biopsies of smokers, CYP1A1, CYP1B1, CYP2C9, GSTP1, and GSTA2 were induced, but CYP2J2 and EPHXI were repressed. Induction of CYP1A1 and CYP1B1 transcript abundance resulted in increased activity of the coded enzyme. Finally, expression of the liver X receptor and the glucocorticoid receptor was significantly up-regulated in bronchoalveolar lavage cells of smokers. Conclusions: We found gene expression of pulmonary xenobiotic metabolizing enzymes and certain key transcription factors to be regulated in bronchoalveolar lavage cells and bronchial biopsies of smokers. The observed changes demonstrate tissue specificity in xenobiotic metabolism, with likely implications for the metabolic activation of procarcinogens to ultimate carcinogens of tobacco smoke.