title: V79 Chinese hamster cells genetically engineered for polymorphic cytochrome P450 2D6 and their predictive value for humans.
abstract: With more than 30 genetic variants human cytochrome P450 2D6 (CYP2D6) presents the most extensive variation among all cytochromes P450. At the same time, roughly 30% of all drugs are metabolised by CYP2D6. Therefore, V79 Chinese hamster cells were genetically engineered for the genetic variants *1, *2, *9, *10, and *17 encoding active enzymes. These cells are to be used to understand and to predict variant-dependent metabolism of drugs and drug candidates. The V79-derived cell lines were extensively characterised for stable expression of mRNA, for enzyme activity using bufuralol hydroxylation, for CYP content by CO difference spectra, and for protein distribution and cellular location by in situ immunofluorescence. Based on these results, CYP-mediated metabolism of tamoxifen was investigated.
authors.affiliation: GenPharmTox BioTech AG, D-Planegg/Martinsried.
authors.forename: Niels
authors.initials: N
authors.lastname: Krebsfaenger
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Mürdter
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Zanger
authors.forename: Michel F
authors.initials: MF
authors.lastname: Eichelbaum
authors.forename: Johannes
authors.initials: J
authors.lastname: Doehmer
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D004347:Drug Interactions; D004983:Ethanolamines / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005818:Genetic Engineering; D014644:Genetic Variation; D005822:Genetic Vectors; D006900:Hydroxylation / Q000187:drug effects; D011110:Polymorphism, Genetic; D011802:Quinidine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000378:metabolism; D013629:Tamoxifen / Q000378:metabolism; D014162:Transfection
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C010831:bufuralol; D019389:Cytochrome P-450 CYP2D6; D011802:Quinidine