Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation.
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 beta-galactosidase 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 (D0 2.022 and 2.153, respectively), or when irradiation was delivered 24 h after coculture (D0 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-beta1, TGF-beta2, TGF-beta3, MIF, TNF-alpha, 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.
Epperly
M W
MW
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, PA 15213, USA.
Defilippi
S
S
Sikora
C
C
Gretton
J
J
Kalend
A
A
Greenberger
J S
JS
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D002470:Cell Survival / Q000528:radiation effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008081:Liposomes; D008168:Lung / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011836:Radiation Tolerance; D013482:Superoxide Dismutase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D008081:Liposomes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013482:Superoxide Dismutase