Department of Radiation Oncology, University of Pittsburgh Cancer Institute, 200 Lothrop Street, B346-PUH, Pittsburgh, PA 15213, USA

Correspondence to: J S Greenberger

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 -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-1, tgf-2, tgf-3, mif, tnf-, 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. Gene Therapy (2000) 7, 1011-1018.

plasmid/liposomes; MnSOD; lung radioprotection