Metabolic activity testing can underestimate acute drug cytotoxicity as revealed by HepG2 cell clones overexpressing cytochrome P450 2C19 and 3A4.


Journal

Toxicology
ISSN: 1879-3185
Titre abrégé: Toxicology
Pays: Ireland
ID NLM: 0361055

Informations de publication

Date de publication:
15 01 2019
Historique:
received: 04 07 2018
revised: 23 11 2018
accepted: 26 11 2018
pubmed: 1 12 2018
medline: 24 5 2019
entrez: 1 12 2018
Statut: ppublish

Résumé

Preclinical drug safety assessment includes in vitro studies with physiologically relevant cell cultures. As an in vitro system for hepatic toxicology testing, we have been generating cell clones of human hepatoblastoma cell line HepG2 by lentiviral transduction of phase I cytochrome P450 (CYP) enzymes. Here, we present a stable CYP2C19-overexpressing HepG2 cell clone (HepG2-2C19 C1) showing an enzyme activity of approximately 82 pmol x min

Identifiants

pubmed: 30500380
pii: S0300-483X(18)30620-6
doi: 10.1016/j.tox.2018.11.008
pii:
doi:

Substances chimiques

Acrolein 7864XYD3JJ
Cyclophosphamide 8N3DW7272P
CYP2C19 protein, human EC 1.14.14.1
Cytochrome P-450 CYP2C19 EC 1.14.14.1
Cytochrome P-450 CYP3A EC 1.14.14.1
CYP3A4 protein, human EC 1.14.14.55

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

37-47

Informations de copyright

Copyright © 2018. Published by Elsevier B.V.

Auteurs

Susanne Steinbrecht (S)

Institute of Biotechnology, Brandenburg University of Technology, Universitätsplatz 1, 01968, Senftenberg, Germany.

Rosalie König (R)

Institute of Biotechnology, Brandenburg University of Technology, Universitätsplatz 1, 01968, Senftenberg, Germany.

Kai-Uwe Schmidtke (KU)

Institute of Biotechnology, Brandenburg University of Technology, Universitätsplatz 1, 01968, Senftenberg, Germany.

Natalie Herzog (N)

Institute of Biotechnology, Brandenburg University of Technology, Universitätsplatz 1, 01968, Senftenberg, Germany.

Katrin Scheibner (K)

Institute of Biotechnology, Brandenburg University of Technology, Universitätsplatz 1, 01968, Senftenberg, Germany.

Anne Krüger-Genge (A)

Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Kantstr. 55, 14513, Teltow, Germany.

Friedrich Jung (F)

Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Kantstr. 55, 14513, Teltow, Germany.

Sarah Kammerer (S)

Institute of Biotechnology, Brandenburg University of Technology, Universitätsplatz 1, 01968, Senftenberg, Germany.

Jan-Heiner Küpper (JH)

Institute of Biotechnology, Brandenburg University of Technology, Universitätsplatz 1, 01968, Senftenberg, Germany. Electronic address: jan-heiner.kuepper@b-tu.de.

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Classifications MeSH