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- Title
Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation.
- Authors
Epperly, M W; Defilippi, S; Sikora, C; Gretton, J; Kalend, A; Greenberger, J S
- Abstract
To determine whether intratracheal (IT) lung protective manganese superoxide-plasmid/liposomes (MnSOD-PL) complex provided 'bystander' protection of thoracic tumors, mice with orthotopic Lewis lung carcinoma-bacterial βgalactosidase gene (3LL-LacZ) were studied. There was no significant difference in irradiation survival of 3LL-LacZ cells irradiated, then cocultured with MnSOD-PL-treated compared with control lung cells (D[sub 0] 2.022 and 2.153, respectively), or when irradiation was delivered 24 h after coculture (D[sub 0] 0.934 and 0.907, respectively). Tumor-bearing control mice showed 50% survival at 18 days and 10% survival at 21 days. Mice receiving liposomes with no insert or LacZ-PL complex plus 18 Gy had 50% survival at 22 days, and a 20% and 30% survival at day 50, respectively. Mice receiving MnSOD-PL complex followed by 18 Gy showed prolonged survival of 45% at 50 days after irradiation (P < 0.001). Nested RT-PCR assay for the human MnSOD transgene demonstrated expression at 24 h in normal lung, but not in orthotopic tumors. Decreased irradiation induction of TGF-β1, TGF-β2, TGF-β3, MIF, TNF-α, and IL-1 at 24 h was detected in lungs, but not orthotopic tumors from MnSOD-PL-injected mice (P < 0.001). Thus, pulmonary radioprotective MnSOD-PL therapy does not provide detectable 'bystander' protection to thoracic tumors.
- Subjects
SUPEROXIDE dismutase; PLASMIDS; LIPOSOMES; TUMORS; IRRADIATION
- Publication
Gene Therapy, 2000, Vol 7, Issue 12, p1011
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301207