title: Human relevance of an in vitro gene signature in HaCaT for skin sensitization.
abstract: The skin sensitizing potential of chemicals is mainly assessed using animal methods, such as the murine local lymph node assay. Recently, an in vitro assay based on a gene expression signature in the HaCaT keratinocyte cell line was proposed as an alternative to these animal methods. Here, the human relevance of this gene signature is assessed through exposure of freshly isolated human skin to the chemical allergens dinitrochlorobenzene (DNCB) and diphenylcyclopropenone (DCP). In human skin, the gene signature shows similar direction of regulation as was previously observed in vitro, suggesting that the molecular processes that drive expression of these genes are similar between the HaCaT cell line and freshly isolated skin, providing evidence for the human relevance of the gene signature.
authors.affiliation: National Institute for Public Health and the Environment (RIVM), PO Box 1, NL-3720BA Bilthoven, The Netherlands; Department of Toxicogenomics, Maastricht University, PO Box 616, NL-6200 MD Maastricht, The Netherlands. Electronic address: jochem.vdveen@gmail.com.
authors.forename: Jochem W
authors.initials: JW
authors.lastname: van der Veen
authors.affiliation: National Institute for Public Health and the Environment (RIVM), PO Box 1, NL-3720BA Bilthoven, The Netherlands.
authors.forename: Henny
authors.initials: H
authors.lastname: Hodemaekers
authors.affiliation: Toxicology and Risk Assessment, TNO Triskelion, PO Box 844, NL-3700 AV Zeist, The Netherlands.
authors.forename: Astrid A
authors.initials: AA
authors.lastname: Reus
authors.affiliation: Toxicology and Risk Assessment, TNO Triskelion, PO Box 844, NL-3700 AV Zeist, The Netherlands.
authors.forename: Wilfred J M
authors.initials: WJ
authors.lastname: Maas
authors.affiliation: National Institute for Public Health and the Environment (RIVM), PO Box 1, NL-3720BA Bilthoven, The Netherlands; Department of Toxicogenomics, Maastricht University, PO Box 616, NL-6200 MD Maastricht, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: van Loveren
authors.affiliation: National Institute for Public Health and the Environment (RIVM), PO Box 1, NL-3720BA Bilthoven, The Netherlands. Electronic address: janine.ezendam@rivm.nl.
authors.forename: Janine
authors.initials: J
authors.lastname: Ezendam
mesh_terms: D000328:Adult; D000485:Allergens / Q000009:adverse effects; D003521:Cyclopropanes / Q000009:adverse effects; D017449:Dermatitis, Allergic Contact / Q000235:genetics* / Q000378:metabolism; D004137:Dinitrochlorobenzene / Q000009:adverse effects; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000485:Allergens; D003521:Cyclopropanes; D004137:Dinitrochlorobenzene; C029402:diphenylcyclopropenone
keywords: Gene signature; HaCaT; Human relevance; Skin sensitization