Validation of in vitro cell models used in drug metabolism and transport studies; genotyping of cytochrome P450, phase II enzymes and drug transporter polymorphisms in the human hepatoma (HepG2), ovarian carcinoma (IGROV-1) and colon carcinoma (CaCo-2, LS180) cell lines

Human cell lines are often used for in vitro biotransformation and transport studies of drugs. In vivo, genetic polymorphisms have been identified in drug-metabolizing enzymes and ABC-drug transporters leading to altered enzyme activity, or a change in the inducibility of these enzymes. These geneti...

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Bibliographic Details
Published in:	Toxicology and applied pharmacology Vol. 211; no. 1; pp. 1 - 10
Main Authors:	Brandon, Esther F.A., Bosch, Tessa M., Deenen, Maarten J., Levink, Rianne, van der Wal, Everdina, van Meerveld, Joyce B.M., Bijl, Monique, Beijnen, Jos H., Schellens, Jan H.M., Meijerman, Irma
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 15-02-2006
Subjects:	60 APPLIED LIFE SCIENCES ANIMAL CELLS ATP-Binding Cassette, Sub-Family B, Member 1 - genetics ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Biological Transport Biotransformation CaCo-2 Caco-2 Cells Carcinoma - enzymology Carcinoma - metabolism Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - metabolism Cell Line, Tumor Colonic Neoplasms - enzymology Colonic Neoplasms - metabolism Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Drug Screening Assays, Antitumor - methods Drug Screening Assays, Antitumor - standards Drug transporters DRUGS ENZYME ACTIVITY ENZYMES Female Genetic polymorphisms HEPATOMAS HepG2 Humans IGROV-1 IN VITRO IN VIVO Inactivation, Metabolic - genetics LARGE INTESTINE Liver Neoplasms - enzymology Liver Neoplasms - metabolism LS180 cytochrome P450 Membrane Transport Proteins - genetics Membrane Transport Proteins - metabolism METABOLISM Ovarian Neoplasms - enzymology Ovarian Neoplasms - genetics Pharmacogenetics - methods Phase II enzymes Polymorphism, Genetic Transferases - genetics Transferases - metabolism VALIDATION CaCo-2 Phase II enzymes IGROV-1 HepG2 LS180 cytochrome P450 Genetic polymorphisms Drug transporters
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Summary:	Human cell lines are often used for in vitro biotransformation and transport studies of drugs. In vivo, genetic polymorphisms have been identified in drug-metabolizing enzymes and ABC-drug transporters leading to altered enzyme activity, or a change in the inducibility of these enzymes. These genetic polymorphisms could also influence the outcome of studies using human cell lines. Therefore, the aim of our study was to pharmacogenotype four cell lines frequently used in drug metabolism and transport studies, HepG2, IGROV-1, CaCo-2 and LS180, for genetic polymorphisms in biotransformation enzymes and drug transporters. The results indicate that, despite the presence of some genetic polymorphisms, no real effects influencing the activity of metabolizing enzymes or drug transporters in the investigated cell lines are expected. However, this characterization will be an aid in the interpretation of the results of biotransformation and transport studies using these in vitro cell models.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0041-008X 1096-0333
DOI:	10.1016/j.taap.2005.05.004