CYP1A1/1B1 and CYP2A6/2A13 activity is conserved in cultures of differentiated primary human tracheobronchial epithelial cells.

Article Details

Citation

Copy to clipboard

Newland N, Baxter A, Hewitt K, Minet E

CYP1A1/1B1 and CYP2A6/2A13 activity is conserved in cultures of differentiated primary human tracheobronchial epithelial cells.

Toxicol In Vitro. 2011 Jun;25(4):922-9. doi: 10.1016/j.tiv.2011.02.014. Epub 2011 Mar 3.

PubMed ID

21376804 [ View in PubMed

]

Abstract

BACKGROUND: The respiratory tract is the primary route of exposure to inhaled toxicants such as environmental pollutants and tobacco smoke. Metabolic activation of xenobiotics is a contributor to the onset of lung diseases. Enzymes such as CYP1A1/1B1 and CYP2A6/2A13 activate polycyclic aromatic hydrocarbons and nitrosamines, respectively. Yet, few in vitro models retaining both adequate morphology and metabolic activities are currently available to investigate smoke toxicity. OBJECTIVE: We characterised the expression and activity of the toxicologically relevant metabolic enzymes CYP1A1/1B1 and CYP2A6/2A13 in polarised primary tracheobronchial epithelial cells cultured at the air-liquid interface. Metabolic activity was compared with NCI-H292 and A549, two commonly used lung epithelial cell models. RESULTS: We report that CYP activity and inducibility is conserved in polarised primary tracheobronchial epithelial cells for 7- and 28-days cultured at the air-liquid interface. In comparison, NCI-H292 cells did not show CYP2A6/2A13 activity whilst A549 cells did not display significant metabolic activity for CYP1A1/1B1 or CYP2A6/2A13. CONCLUSION: Primary tracheobronchial epithelial cells retain both a polarised morphology and significant metabolic activity over a prolonged period of time. On the other hand, although A549 cells and NCI-H292 cells have been extensively used as lung models for toxicological assessment, they lack critical metabolic activation capability.