Xenobiotic metabolism and disposition in human lung cell models: comparison with in vivo expression profiles.
Numerous lung cell lines are currently used as in vitro models for pharmacological and toxicological studies. However, no exhaustive report about the metabolic capacities of these models in comparison with those of lung tissues is available. In the present study, we used a high-throughput quantitative real-time reverse transcription-polymerase chain reaction strategy to characterize the expression profiles of 380 genes encoding proteins involved in the metabolism and disposition of xenobiotics in 10 commonly used lung cell lines (A549, H292, H358, H460, H727, Calu-1, 16HBE, 1 HAEO, BEAS-2B, and L-132) and four primary cultures of human bronchial epithelial cells. Expression results were then compared with those previously obtained in human nontumoral and tumoral lung tissues. Our results revealed disparities in gene expression between lung cell lines or when comparing lung cell lines with primary cells or lung tissues. Primary cell cultures displayed the highest similarities with bronchial mucosa in terms of transcript profiling and therefore seem to be the most relevant in vitro model for investigating the metabolism and bioactivation of toxicants and drugs in bronchial epithelium. H292 and BEAS-2B cell lines, which exhibited the highest homology in gene expression pattern with primary cells and the lowest number of dysregulated genes compared with nontumoral lung tissues, could be used as surrogates for toxicological and pharmacological studies. Overall, our study should provide references for researchers to choose the most appropriate in vitro model for analyzing the cellular effects of drugs or airborne toxicants on the airway.
Faculté de Médecine H. Warembourg, Pôle Recherche, Lille, France.
Elisabeth
E
Courcot
Julie
J
Leclerc
Jean-Jacques
JJ
Lafitte
Eric
E
Mensier
Sophie
S
Jaillard
Philippe
P
Gosset
Pirouz
P
Shirali
Nicolas
N
Pottier
Franck
F
Broly
Jean-Marc
JM
Lo-Guidice
D001711:Biotransformation / Q000235:genetics; D001980:Bronchi / Q000378:metabolism; D002460:Cell Line; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D057166:High-Throughput Screening Assays; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015262:Xenobiotics / Q000378:metabolism*
D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D015262:Xenobiotics