Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy

M. Epperly, J. Bray, S. Kraeger, R. Zwacka, J. Engelhardt, E. Travis, J. S. Greenberger

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Organ and tissue damage caused by ionizing irradiation is directly related to volume irradiated, total dose and dose rate. The acute effects are in part mediated by cellular activation of early response genes, including those for transcriptional activators of genes for humoral cytokines. In the lung, as in other organs, recovery from the acute effects of ionizing irradiation does not always correlate with prevention of the critical fate effects, including fibrosis, which contribute to organ failure. An interventional technique by which to protect normal organs from the late effects of irradiation has remained elusive. We now demonstrate that overexpression of a transgene for human manganese superoxide dismutase (MnSOD) delivered by plasmid-liposome, or adenovirus to the lungs of C57BL/6J or Nu/J mice, respectively, before irradiation exposure, decreases the late effects of whole lung irradiation (organizing alveolitis/fibrosis). These data provide a rational basis for the design of gene therapy approaches to organ protection from irradiation damage.

Original languageEnglish (US)
Pages (from-to)196-208
Number of pages13
JournalGene Therapy
Volume5
Issue number2
DOIs
StatePublished - Jan 1 1998

Fingerprint

Genetic Therapy
Superoxide Dismutase
Lung
Fibrosis
Transgenes
Adenoviridae
Liposomes
Genes
Plasmids
Cytokines

Keywords

  • Late effects
  • MnSOD
  • Radiation fibrosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Epperly, M., Bray, J., Kraeger, S., Zwacka, R., Engelhardt, J., Travis, E., & Greenberger, J. S. (1998). Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. Gene Therapy, 5(2), 196-208. https://doi.org/10.1038/sj.gt.3300580

Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. / Epperly, M.; Bray, J.; Kraeger, S.; Zwacka, R.; Engelhardt, J.; Travis, E.; Greenberger, J. S.

In: Gene Therapy, Vol. 5, No. 2, 01.01.1998, p. 196-208.

Research output: Contribution to journalArticle

Epperly, M, Bray, J, Kraeger, S, Zwacka, R, Engelhardt, J, Travis, E & Greenberger, JS 1998, 'Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy', Gene Therapy, vol. 5, no. 2, pp. 196-208. https://doi.org/10.1038/sj.gt.3300580
Epperly, M. ; Bray, J. ; Kraeger, S. ; Zwacka, R. ; Engelhardt, J. ; Travis, E. ; Greenberger, J. S. / Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. In: Gene Therapy. 1998 ; Vol. 5, No. 2. pp. 196-208.
@article{9cab48496e194e7ea650ae662c5f7149,
title = "Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy",
abstract = "Organ and tissue damage caused by ionizing irradiation is directly related to volume irradiated, total dose and dose rate. The acute effects are in part mediated by cellular activation of early response genes, including those for transcriptional activators of genes for humoral cytokines. In the lung, as in other organs, recovery from the acute effects of ionizing irradiation does not always correlate with prevention of the critical fate effects, including fibrosis, which contribute to organ failure. An interventional technique by which to protect normal organs from the late effects of irradiation has remained elusive. We now demonstrate that overexpression of a transgene for human manganese superoxide dismutase (MnSOD) delivered by plasmid-liposome, or adenovirus to the lungs of C57BL/6J or Nu/J mice, respectively, before irradiation exposure, decreases the late effects of whole lung irradiation (organizing alveolitis/fibrosis). These data provide a rational basis for the design of gene therapy approaches to organ protection from irradiation damage.",
keywords = "Late effects, MnSOD, Radiation fibrosis",
author = "M. Epperly and J. Bray and S. Kraeger and R. Zwacka and J. Engelhardt and E. Travis and Greenberger, {J. S.}",
year = "1998",
month = "1",
day = "1",
doi = "10.1038/sj.gt.3300580",
language = "English (US)",
volume = "5",
pages = "196--208",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy

AU - Epperly, M.

AU - Bray, J.

AU - Kraeger, S.

AU - Zwacka, R.

AU - Engelhardt, J.

AU - Travis, E.

AU - Greenberger, J. S.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - Organ and tissue damage caused by ionizing irradiation is directly related to volume irradiated, total dose and dose rate. The acute effects are in part mediated by cellular activation of early response genes, including those for transcriptional activators of genes for humoral cytokines. In the lung, as in other organs, recovery from the acute effects of ionizing irradiation does not always correlate with prevention of the critical fate effects, including fibrosis, which contribute to organ failure. An interventional technique by which to protect normal organs from the late effects of irradiation has remained elusive. We now demonstrate that overexpression of a transgene for human manganese superoxide dismutase (MnSOD) delivered by plasmid-liposome, or adenovirus to the lungs of C57BL/6J or Nu/J mice, respectively, before irradiation exposure, decreases the late effects of whole lung irradiation (organizing alveolitis/fibrosis). These data provide a rational basis for the design of gene therapy approaches to organ protection from irradiation damage.

AB - Organ and tissue damage caused by ionizing irradiation is directly related to volume irradiated, total dose and dose rate. The acute effects are in part mediated by cellular activation of early response genes, including those for transcriptional activators of genes for humoral cytokines. In the lung, as in other organs, recovery from the acute effects of ionizing irradiation does not always correlate with prevention of the critical fate effects, including fibrosis, which contribute to organ failure. An interventional technique by which to protect normal organs from the late effects of irradiation has remained elusive. We now demonstrate that overexpression of a transgene for human manganese superoxide dismutase (MnSOD) delivered by plasmid-liposome, or adenovirus to the lungs of C57BL/6J or Nu/J mice, respectively, before irradiation exposure, decreases the late effects of whole lung irradiation (organizing alveolitis/fibrosis). These data provide a rational basis for the design of gene therapy approaches to organ protection from irradiation damage.

KW - Late effects

KW - MnSOD

KW - Radiation fibrosis

UR - http://www.scopus.com/inward/record.url?scp=0031887093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031887093&partnerID=8YFLogxK

U2 - 10.1038/sj.gt.3300580

DO - 10.1038/sj.gt.3300580

M3 - Article

C2 - 9578839

AN - SCOPUS:0031887093

VL - 5

SP - 196

EP - 208

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 2

ER -