title: Tissue-engineered mucosa is a suitable model to quantify the acute biological effects of ionizing radiation.
abstract: The aim of this study was to evaluate the suitability of tissue-engineered mucosa (TEM) as a model for studying the acute effects of ionizing radiation (IR) on the oral mucosa. TEM and native non-keratinizing oral mucosa (NNOM) were exposed to a single dose of 16.5Gy and harvested at 1, 6, 24, 48, and 72h post-irradiation. DNA damage induced by IR was determined using p53 binding protein 1 (53BP1), and DNA repair was determined using Rad51. Various components of the epithelial layer, basement membrane, and underlying connective tissue were analyzed using immunohistochemistry. The expression of cytokines interleukin-1β (IL-1β) and transforming growth factor beta 1 (TGF-β1) was analyzed using an enzyme-linked immunosorbent assay. The expression of DNA damage protein 53BP1 and repair protein Rad51 were increased post-irradiation. The expression of keratin 19, vimentin, collage type IV, desmoglein 3, and integrins α6 and β4 was altered post-irradiation. Proliferation significantly decreased at 24, 48, and 72h post-irradiation in both NNOM and TEM. IR increased the secretion of IL-1β, whereas TGF-β1 secretion was not altered. All observed IR-induced alterations in TEM were also observed in NNOM. Based on the similar response of TEM and NNOM to IR we consider our TEM construct a suitable model to quantify the acute biological effects of IR.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Erasmus MC, Rotterdam, The Netherlands. wendy_tra@hotmail.com
authors.forename: W M W
authors.initials: WM
authors.lastname: Tra
authors.forename: B
authors.initials: B
authors.lastname: Tuk
authors.forename: J W
authors.initials: JW
authors.lastname: van Neck
authors.forename: S E R
authors.initials: SE
authors.lastname: Hovius
authors.forename: S
authors.initials: S
authors.lastname: Perez-Amodio
mesh_terms: D001485:Basement Membrane / Q000528:radiation effects; D002448:Cell Adhesion / Q000528:radiation effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D024141:Collagen Type IV / Q000032:analysis / Q000528:radiation effects; D003238:Connective Tissue / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D051184:Desmoglein 3 / Q000032:analysis / Q000528:radiation effects; D004848:Epithelium / Q000528:radiation effects; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D039503:Integrin alpha6 / Q000032:analysis / Q000528:radiation effects; D039663:Integrin beta4 / Q000032:analysis / Q000528:radiation effects; D053583:Interleukin-1beta / Q000032:analysis / Q000528:radiation effects; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000528:radiation effects; D053539:Keratin-19 / Q000032:analysis / Q000528:radiation effects; D015603:Keratinocytes / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology / Q000528:radiation effects*; D051135:Rad51 Recombinase / Q000032:analysis / Q000528:radiation effects; D011829:Radiation Dosage; D023822:Tissue Engineering; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000528:radiation effects; D000071857:Tumor Suppressor p53-Binding Protein 1; D014746:Vimentin / Q000032:analysis / Q000528:radiation effects
chemical_list: D024141:Collagen Type IV; D051184:Desmoglein 3; D039503:Integrin alpha6; D039663:Integrin beta4; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D053539:Keratin-19; C498301:TP53BP1 protein, human; D053773:Transforming Growth Factor beta1; D000071857:Tumor Suppressor p53-Binding Protein 1; D014746:Vimentin; C495153:RAD51 protein, human; D051135:Rad51 Recombinase