XENOBIOTIC METABOLISM ENZYME GENE-EXPRESSION IN HUMAN BRONCHIAL EPITHELIAL AND ALVEOLAR MACROPHAGE CELLS

Human bronchial epithelial cells (BEC), a primary defense against inha led materials, are the progenitor cells for bronchogenic carcinomas an d have important metabolic capabilities. We used reverse transcriptase -polymerase chain reaction (RT-PCR) to identify xenobiotic metabolism enzymes expressed in primary BEC and alveolar macrophages (AM) of non- smoking volunteers. Cytochromes P450 (CYP) 1A1, 1B1, 2B7, 2E1, and 4B1 and microsomal epoxide hydrolase (mEH) were expressed in BEC but not AM. CYP2F1 was expressed in BEC, but it was expressed at barely detect able levels or not at all in AM. NADPH oxidoreductase (NADPH OR), micr osomal glutathione transferase (GST 12), glutathione transferase mu, p henol sulfouansferase (PST), thermolabile phenol sulfotransferase (TL PST), and the clara cell-specific gene, CC10 were expressed in both BE C and AM. CYP3A4 and glucuronosyl transferases-1 and 2 were not expres sed in either BEC or AM. In contrast to primary BEC, of the genes eval uated, the immortalized human bronchial epithelial cell line BEP2D con stitutively expressed only CYP1A1, CYP2E1, NADPH OR, glucuronosyl tran sferase 1, GST 12, GST mu, PST, TL PST, and CC10. The loss of xenobiot ic metabolism enzyme gene expression in the BEP2D cell line may result from either reduced exposure to inducing agents, or loss of different iative characteristics in culture. It is clear from the data comparing BEC and AM that there are important intertissue differences in expres sion of xenobiotic metabolism enzymes.