title: Development and evaluation of a skin organ model for the analysis of radiation effects.
abstract: OBJECTIVE
  The reaction of tissues to ionizing radiation involves alterations in cell-cell and cell-matrix interactions mediated by cellular adhesion molecules. The aim of this study was to develop and evaluate an artificial skin organ model for the analysis of radiation effects.
  
  
  METHODS
  A human co-culture system consisting of the spontaneously immortalized keratinocyte cell line HaCaT and primary HDFa fibroblasts embedded into a collagen sponge was established. This skin organ model has been characterized and evaluated for its suitability for radiobiological investigations. For that purpose, expression of beta(1)-integrin following irradiation was compared in the skin organ model and in HaCaT monolayer cells (FACScan and immunohistochemistry). Furthermore, the influence of ionizing radiation on DNA fragmentation was investigated in the skin organ model (TUNEL assay).
  
  
  RESULTS
  The novel skin organ model showed characteristics of human skin as demonstrated by cytokeratin and Ki-67 immunoreactivity and by electron microscopy. A single dose of 5 Gy X-irradiation induced an upregulation of beta(1)-integrin expression both in the skin organ model and in HaCaT cells. Following irradiation, beta(1)-integrin immunoreactivity was intensified in the upper layers of the epidermis equivalent whereas it was almost absent in the deeper layers. Additionally, irradiation of the skin organ model also caused a marked increase of DNA fragmentation.
  
  
  CONCLUSIONS
  These results demonstrate that the novel skin organ model is suitable to investigate cellular radiation effects under three-dimensional conditions. This allows to investigate radiation effects which cannot be demonstrated in monolayer cell cultures.
authors.affiliation: Institute of Radiobiology of the German Armed Forces, Munich, Germany. ViktorMeineke@bundeswehr.org
authors.forename: Viktor
authors.initials: V
authors.lastname: Meineke
authors.forename: Kerstin
authors.initials: K
authors.lastname: Müller
authors.forename: Roland
authors.initials: R
authors.lastname: Ridi
authors.forename: Nils
authors.initials: N
authors.lastname: Cordes
authors.forename: Frank-Michael
authors.initials: FM
authors.lastname: Köhn
authors.forename: Artur
authors.initials: A
authors.lastname: Mayerhofer
authors.forename: Johannes
authors.initials: J
authors.lastname: Ring
authors.forename: Dirk
authors.initials: D
authors.lastname: van Beuningen
mesh_terms: D002461:Cell Line, Transformed; D003094:Collagen; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000473:pathology / Q000528:radiation effects*; D008854:Microscopy, Electron; D008954:Models, Biological; D011855:Radiodermatitis / Q000473:pathology*; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: D019012:Integrin beta1; D003094:Collagen