Gene transfer of human manganese superoxide dismutase protects small intestinal villi from radiation injury

Hong Liang Guo, Darren Wolfe, Michael W. Epperly, Shaohua Huang, Kaihong Liu, Joseph C. Glorioso, Joel Greenberger, David Blumberg, D. I. Soybel, M. G. Sarr, R. A. Hodin

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Small bowel toxicity represents a major dose-limiting side effect of radiation treatment for many malignancies. We examined the effects of overexpressing human manganese superoxide dismutase (MnSOD) in the small intestine in mice to prevent radiation enteritis. Mice were treated with the human MnSOD gene delivered enterally using a nontoxic, replication-defective herpes simplex virus (HSV)-1-based vector. HSV vectors containing the human MnSOD transgene and green fluorescent protein (GFP) transgene, or GFP transgene alone, were constructed and injected intraluminally into a 2cm length of small intestine of C3H/HeNsd mice. Total body irradiation of 15 Gy was delivered to mice inoculated 24 hours earlier with either HSV-MnSOD (10 3 to 10 8 plaque-forming units), control HSV-GFP, or no vector. At 24 or 72 hours after irradiation, mice were killed and villi areas were measured from appropriate segments of the small intestine. Control irradiated mice showed a decreased villi area of 82% by day 3 after irradiation, whereas treatment of mice with HSV-MnSOD 10 8 plaque-forming units led to only a 16% decrease in villi area (P < 0.001) before radiation. Similar findings were seen on day 3 and were associated with a significant (P < 0.001) preservation of enteric protein content in HSV-MnSOD-treated mice. A dose-dependent effect of MnSOD in preventing radiation-induced small bowel injury was evident. These data demonstrate that overexpression of human MnSOD via a replication-defective herpes viral vector is an efficacious method of protecting the small intestine from ionizing radiation damage.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalJournal of Gastrointestinal Surgery
Volume7
Issue number2
DOIs
StatePublished - Feb 2003
Externally publishedYes

Fingerprint

Radiation Injuries
Superoxide Dismutase
Simplexvirus
Genes
Small Intestine
Green Fluorescent Proteins
Transgenes
Radiation
Defective Viruses
Enteritis
Inbred C3H Mouse
Whole-Body Irradiation
Radiation Effects
Human Herpesvirus 1
Ionizing Radiation
Wounds and Injuries
Therapeutics

Keywords

  • Gene therapy
  • MnSOD
  • Radiation damage
  • Small intestine

ASJC Scopus subject areas

  • Surgery

Cite this

Gene transfer of human manganese superoxide dismutase protects small intestinal villi from radiation injury. / Guo, Hong Liang; Wolfe, Darren; Epperly, Michael W.; Huang, Shaohua; Liu, Kaihong; Glorioso, Joseph C.; Greenberger, Joel; Blumberg, David; Soybel, D. I.; Sarr, M. G.; Hodin, R. A.

In: Journal of Gastrointestinal Surgery, Vol. 7, No. 2, 02.2003, p. 229-236.

Research output: Contribution to journalArticle

Guo, HL, Wolfe, D, Epperly, MW, Huang, S, Liu, K, Glorioso, JC, Greenberger, J, Blumberg, D, Soybel, DI, Sarr, MG & Hodin, RA 2003, 'Gene transfer of human manganese superoxide dismutase protects small intestinal villi from radiation injury', Journal of Gastrointestinal Surgery, vol. 7, no. 2, pp. 229-236. https://doi.org/10.1016/S1091-255X(02)00186-5
Guo, Hong Liang ; Wolfe, Darren ; Epperly, Michael W. ; Huang, Shaohua ; Liu, Kaihong ; Glorioso, Joseph C. ; Greenberger, Joel ; Blumberg, David ; Soybel, D. I. ; Sarr, M. G. ; Hodin, R. A. / Gene transfer of human manganese superoxide dismutase protects small intestinal villi from radiation injury. In: Journal of Gastrointestinal Surgery. 2003 ; Vol. 7, No. 2. pp. 229-236.
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