title: Human skin in organ culture and human skin cells (keratinocytes and fibroblasts) in monolayer culture for assessment of chemically induced skin damage.
abstract: Human skin cells (epidermal keratinocytes and dermal fibroblasts) in monolayer culture and human skin in organ culture were exposed to agents that are known to produce irritation (redness, dryness, edema and scaly crusts) when applied topically to skin. Among the agents used were three well accepted contact irritants (i.e., all-trans retinoic acid [RA], sodium lauryl sulfate [SLS] and benzalkonium chloride) as well as the corrosive organic mercury compound, aminophenyl mercuric acetate (APMA), and 5 contact sensitizers (oxazolone, nickel sulfate, eugenol, isoeugenol and ethylene glycol dimethacrylate [EGDM]). As a group, the contact irritants (including the corrosive mercuric compound) were cytotoxic for keratinocytes and fibroblasts and suppressed growth at lower concentrations than the contact sensitizers. The contact irritants also produced histological changes (hyperplasia, incomplete keratinization, loss of the granular layer, acantholysis and necrosis) in organ-cultured skin at dose levels at which the contact sensitizers appeared to be inert. Finally, the profile of secreted molecules from organ-cultured skin was different in the presence of contact irritants versus contact sensitizers. Taken together, these data suggest that the use of organ-cultured skin in conjunction with cells derived from the skin in monolayer culture may provide an initial approach to screening agents for deleterious changes in skin.
authors.affiliation: Department of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. varani@umich.edu
authors.forename: James
authors.initials: J
authors.lastname: Varani
authors.forename: Patricia
authors.initials: P
authors.lastname: Perone
authors.forename: Diana M
authors.initials: DM
authors.lastname: Spahlinger
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Singer
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Diegel
authors.forename: Walter F
authors.initials: WF
authors.lastname: Bobrowski
authors.forename: Robert
authors.initials: R
authors.lastname: Dunstan
mesh_terms: D066258:Amphiregulin; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D066255:EGF Family of Proteins; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007509:Irritants / Q000633:toxicity; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D024042:Collagen Type I; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D007509:Irritants