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 superoxid e-plasmid/liposomes (MnSOD-PL) complex provided 'bystander' protection of t horacic tumors, mice with orthotopic Lewis lung carcinoma-bacterial beta-ga lactosidase gene (3LL-LacZ) were studied. There was no significant differen ce in irradiation survival of 3LL-LacZ cells irradiated, then cocultured wi th MnSOD-PL-treated compared with control lung cells (D-0 2.022 and 2.153, respectively), or when irradiation was delivered 24 h after coculture (D-0 0.934 and 0.907, respectively). Tumor-bearing control mice showed 50% survi val at 18 days and 10% survival at 21 days. Mice receiving liposomes with n o insert or LacZ-PL complex plus 18 Gy had 50% survival at 22 days, and a 2 0% and 30% survival at day 50, respectively. Mice receiving MnSOD-PL comple x followed by 18 Gy showed prolonged survival of 45% at 50 days after irrad iation (P < 0.001). Nested RT-PCR assay for the human MnSOD transgene demon strated expression at 24 h in normal lung, but not in orthotopic tumors. De creased irradiation induction of TGF-beta 1, TGF-beta 2, TGF-beta 3, MIF, T NF-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 M nSOD-PL therapy does not provide detectable 'bystander' protection to thora cic tumors.