Document Detail


Xenobiotic Metabolism and Disposition in Human Lung Cell Models: Comparison with In Vivo Expression Profiles.
MedLine Citation:
PMID:  22798553     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 RT-PCR strategy to characterize the expression profiles of 380 genes encoding proteins involved in the metabolism and disposition of xenobiotics in ten 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 to those previously obtained in human non tumoral 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 appear 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 to non-tumoral 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 airways.
Authors:
Elisabeth Courcot; Julie Leclerc; Jean-Jacques Lafitte; Eric Mensier; Sophie Jaillard; Philippe Gosset; Pirouz Shirali; Nicolas Pottier; Franck Broly; Jean-Marc Lo-Guidice
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-13
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  -     ISSN:  1521-009X     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Universite de Lille 2;
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