AdLTR2EF1α-FGF2-mediated prevention of fractionated irradiation-induced salivary hypofunction in swine

Gene Ther. 2014 Oct;21(10):866-73. doi: 10.1038/gt.2014.63. Epub 2014 Jul 17.


Patients frequently experience a loss of salivary function following irradiation (IR) for the treatment of an oral cavity and oropharyngeal cancer. Herein, we tested if transfer of fibroblast growth factor-2 (FGF2) cDNA could limit salivary dysfunction after fractionated IR (7.5 or 9 Gy for 5 consecutive days to one parotid gland) in the miniature pig (minipig). Parotid salivary flow rates steadily decreased by 16 weeks post-IR, whereas blood flow in the targeted parotid gland began to decrease ~3 days after beginning IR. By 2 weeks, post-IR salivary blood flow was reduced by 50%, at which point it remained stable for the remainder of the study. The single preadministration of a hybrid serotype 5 adenoviral vector encoding FGF2 (AdLTR2EF1a-FGF2) resulted in the protection of parotid microvascular endothelial cells from IR damage and significantly limited the decline of parotid salivary flow. Our results suggest that a local treatment directed at protecting salivary gland endothelial cells may be beneficial for patients undergoing IR for oral cavity and oropharyngeal cancer.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dependovirus / genetics
  • Endothelial Cells / metabolism
  • Endothelial Cells / radiation effects
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Genetic Therapy
  • Genetic Vectors / administration & dosage*
  • Parotid Gland / cytology
  • Parotid Gland / physiopathology*
  • Parotid Gland / radiation effects
  • Radiation Injuries, Experimental / pathology
  • Radiation Injuries, Experimental / prevention & control*
  • Saliva / cytology
  • Saliva / radiation effects
  • Swine
  • Swine, Miniature


  • Fibroblast Growth Factor 2