title: Xenobiotic metabolism capacities of human skin in comparison with a 3D epidermis model and keratinocyte-based cell culture as in vitro alternatives for chemical testing: activating enzymes (Phase I).
abstract: Skin is important for the absorption and metabolism of exposed chemicals such as cosmetics or pharmaceuticals. The Seventh Amendment to the EU Cosmetics Directive prohibits the use of animals for cosmetic testing for certain endpoints, such as genotoxicity; therefore, there is an urgent need to understand the xenobiotic metabolizing capacities of human skin and to compare these activities with reconstructed 3D skin models developed to replace animal testing. We have measured Phase I enzyme activities of cytochrome P450 (CYP) and cyclooxygenase (COX) in ex vivo human skin, the 3D skin model EpiDerm™ (EPI-200), immortalized keratinocyte-based cell lines and primary normal human epidermal keratinocytes. Our data demonstrate that basal CYP enzyme activities are very low in whole human skin and EPI-200 as well as keratinocytes. In addition, activities in monolayer cells differed from organotypic tissues after induction. COX activity was similar in skin, EPI-200 and NHEK cells, but was significantly lower in immortalized keratinocytes. Hence, the 3D model EPI-200 might represent a more suitable model for dermatotoxicological studies. Altogether, these data help to better understand skin metabolism and expand the knowledge of in vitro alternatives used for dermatotoxicity testing.
authors.affiliation: Leibniz-Institut für Umweltmedizinische Forschung (IUF), Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Götz
authors.forename: Roland
authors.initials: R
authors.lastname: Pfeiffer
authors.forename: Julia
authors.initials: J
authors.lastname: Tigges
authors.forename: Veronika
authors.initials: V
authors.lastname: Blatz
authors.forename: Christine
authors.initials: C
authors.lastname: Jäckh
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Freytag
authors.forename: Eric
authors.initials: E
authors.lastname: Fabian
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
authors.forename: Hans F
authors.initials: HF
authors.lastname: Merk
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Edwards
authors.forename: Camilla
authors.initials: C
authors.lastname: Pease
authors.forename: Carsten
authors.initials: C
authors.lastname: Goebel
authors.forename: Nicola
authors.initials: N
authors.lastname: Hewitt
authors.forename: Ellen
authors.initials: E
authors.lastname: Fritsche
mesh_terms: D000826:Animal Testing Alternatives; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003885:Dermotoxins; D015232:Dinoprostone / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008748:Methylcholanthrene; D008954:Models, Biological; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014116:Toxicology; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D001551:Benz(a)Anthracenes; D003885:Dermotoxins; D015262:Xenobiotics; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone