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 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.
Department of Biomedical Analysis, Section of Drug Toxicology, Faculty of Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
Esther F A
EF
Brandon
Tessa M
TM
Bosch
Maarten J
MJ
Deenen
Rianne
R
Levink
Everdina
E
van der Wal
Joyce B M
JB
van Meerveld
Monique
M
Bijl
Jos H
JH
Beijnen
Jan H M
JH
Schellens
Irma
I
Meijerman
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D001711:Biotransformation; D018938:Caco-2 Cells; D002277:Carcinoma / Q000201:enzymology / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods / Q000592:standards*; D005260:Female; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D014166:Transferases / Q000235:genetics* / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D026901:Membrane Transport Proteins; D003577:Cytochrome P-450 Enzyme System; D014166:Transferases