Prevention of radiation-induced oral cavity mucositis by plasmid/liposome delivery of the human manganese superoxide dismutase (SOD2) transgene.
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.
Guo
Hongliang
H
Department of Radiation Oncology, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
Seixas-Silva
Jose A
JA
Epperly
Michael W
MW
Gretton
Joan E
JE
Shin
Dong M
DM
Bar-Sagi
Dafna
D
Archer
Herbert
H
Greenberger
Joel S
JS
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D007763:Lac Operon; D008081:Liposomes / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009061:Mouth Mucosa / Q000473:pathology* / Q000528:radiation effects*; D009092:Mucous Membrane / Q000473:pathology; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*; D013997:Time Factors; D014059:Tongue / Q000473:pathology / Q000528:radiation effects; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
D008081:Liposomes; D013482:Superoxide Dismutase; D001616:beta-Galactosidase