Prevention of radiation-induced oral cavity mucositis by plasmid/liposome delivery of the human manganese superoxide dismutase (SOD2) transgene

Radiat Res. 2003 Mar;159(3):361-70. doi: 10.1667/0033-7587(2003)159[0361:porioc];2.


Oral cavity mucositis is a major toxicity of radiation therapy for head and neck cancer. In the present mouse model studies, we evaluated intraoral administration of SOD2-PL complexes 24 h before single-fraction 30-Gy irradiation for the prevention of oral cavity mucositis. Expression of the human SOD2 transgene in the oral cavity of C3H/HeNsd mice was demonstrated by nested reverse transcriptase polymerase chain reaction (RT-PCR). Mice treated intraorally with bacterial beta-galactosidase gene-plasmid/liposome (LacZ-PL) or hemagglutinin (HA)-manganese superoxide dismutase-plasmid/liposome (HA-SOD2-PL) demonstrated LacZ or HA-SOD2 expression, respectively, 24 h after injection. In a second strain of mouse, SOD2-PL-treated female athymic nude mice demonstrated significantly decreased ulceration at day 5 after 30 Gy, compared to LacZ-PL-injected, irradiated mice or irradiated controls. No further reduction in radiation-induced ulceration was detected in mice treated with both SOD2-PL and 10 mg/kg of amifostine (WR-2721) 30 min before 30 Gy compared to SOD2-PL alone. No significant protection of orthotopically transplanted murine squamous cell carcinoma (SCC-VII) tumors was detected in mice that received SOD2-PL treatment before 18 Gy. Thus overexpression of human SOD2 in the oral cavity mucosa can prevent radiation-induced mucositis with no detectable compromise in the therapeutic response of orthotopically transplanted tumors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / pathology
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Female
  • Genetic Vectors*
  • Humans
  • Immunohistochemistry
  • Lac Operon
  • Liposomes / metabolism*
  • Mice
  • Mice, Nude
  • Mouth Mucosa / pathology*
  • Mouth Mucosa / radiation effects*
  • Mucous Membrane / pathology
  • Neoplasm Transplantation
  • Plasmids / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Superoxide Dismutase / genetics*
  • Time Factors
  • Tongue / pathology
  • Tongue / radiation effects
  • Transgenes*
  • beta-Galactosidase / metabolism


  • Liposomes
  • Superoxide Dismutase
  • beta-Galactosidase