V79 Chinese hamster cells genetically engineered for polymorphic cytochrome P450 2D6 and their predictive value for humans.
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.
Krebsfaenger
Niels
N
GenPharmTox BioTech AG, D-Planegg/Martinsried.
Mürdter
Thomas E
TE
Zanger
Ulrich M
UM
Eichelbaum
Michel F
MF
Doehmer
Johannes
J
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
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