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

• 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
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2005.05.004

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.