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Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation

Gene Therapy volume 7, pages 1011–1018 (2000)Cite this article

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 β-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-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.

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Acknowledgements

This paper is supported in part by the National Institutes of Health, research grant No. RO1-HL60132. We thank Valerie Dewald, RTT, for technical assistance, and Dr William Gooding for the biostatistics. This paper was supported by Research Grants RO1-HL-60132 of the National Institutes of Health.

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

    MW Epperly, S Defilippi, C Sikora, J Gretton, A Kalend & JS Greenberger

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Epperly, M., Defilippi, S., Sikora, C. et al. Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation. Gene Ther 7, 1011–1018 (2000). https://doi.org/10.1038/sj.gt.3301207

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