Tissue-engineered mucosa is a suitable model to quantify the acute biological effects of ionizing radiation

Int J Oral Maxillofac Surg. 2013 Aug;42(8):939-48. doi: 10.1016/j.ijom.2013.01.025. Epub 2013 Apr 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basement Membrane / radiation effects
  • Cell Adhesion / radiation effects
  • Cell Culture Techniques
  • Cell Differentiation / radiation effects
  • Cell Proliferation / radiation effects
  • Collagen Type IV / analysis
  • Collagen Type IV / radiation effects
  • Connective Tissue / radiation effects
  • DNA Damage / radiation effects
  • DNA Repair / radiation effects
  • Desmoglein 3 / analysis
  • Desmoglein 3 / radiation effects
  • Epithelium / radiation effects
  • Female
  • Fibroblasts / radiation effects
  • Gamma Rays
  • Humans
  • Integrin alpha6 / analysis
  • Integrin alpha6 / radiation effects
  • Integrin beta4 / analysis
  • Integrin beta4 / radiation effects
  • Interleukin-1beta / analysis
  • Interleukin-1beta / radiation effects
  • Intracellular Signaling Peptides and Proteins / analysis
  • Intracellular Signaling Peptides and Proteins / radiation effects
  • Keratin-19 / analysis
  • Keratin-19 / radiation effects
  • Keratinocytes / radiation effects
  • Male
  • Middle Aged
  • Mouth Mucosa / cytology
  • Mouth Mucosa / radiation effects*
  • Rad51 Recombinase / analysis
  • Rad51 Recombinase / radiation effects
  • Radiation Dosage
  • Tissue Engineering*
  • Transforming Growth Factor beta1 / analysis
  • Transforming Growth Factor beta1 / radiation effects
  • Tumor Suppressor p53-Binding Protein 1
  • Vimentin / analysis
  • Vimentin / radiation effects

Substances

  • Collagen Type IV
  • Desmoglein 3
  • Integrin alpha6
  • Integrin beta4
  • Interleukin-1beta
  • Intracellular Signaling Peptides and Proteins
  • Keratin-19
  • TP53BP1 protein, human
  • Transforming Growth Factor beta1
  • Tumor Suppressor p53-Binding Protein 1
  • Vimentin
  • RAD51 protein, human
  • Rad51 Recombinase