Modulation of radiation-induced life shortening by systemic intravenous MnSOD-plasmid liposome gene therapy

被引:35
作者
Epperly, Michael W.
Dixon, Tracy
Wang, Hong
Schlesselman, James
Franicola, Darcy
Greenberger, Joel S. [1 ]
机构
[1] Univ Pittsburgh, Med Ctr, Dept Radiat Oncol, Inst Canc, Pittsburgh, PA 15213 USA
关键词
D O I
10.1667/RR1286.1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
To determine whether systemic administration of MnSOD-PL protected mice from the acute hematopoietic syndrome and delayed death after total-body irradiation (TBI), C57BL/ 6,1 mice were injected intravenously with 100 mu l liposomes containing 100 jig of human MnSOD-transgene plasmid 24 h prior to irradiation with 9.5 Gy or 1.0 Gy. The dose of 9.5 Gy was lethal to 42% of irradiated control female mice and 74% of irradiated control male mice at 30 days, with bone marrow hypocellularity consistent with the hematopoietic syndrome. A statistically significant increase in survival was observed in MnSOD-PL-treated female mice out to 400 days and in male mice out to 340 days. The incidence of tumors was similar between surviving groups. Between 350 and 600 days, the outcome was similar for both MnSOD-PL-treated and control irradiated groups. consistent with aging, with no difference in gross or microscopic pathological evidence of tumors. Male and female mice receiving 1.0 Gy TBI showed radiation-induced life shortening after 120 days that was decreased by MnSOD-PL administration and that was not associated,with in increase in rate of tumor-associated death. Therefore, systemic MnSOD-PL radioprotective gene therapy is not associated with a detectably higher incidence of late carcinogenesis. (C) 2008 by Radiation Research Society.
引用
收藏
页码:437 / 443
页数:7
相关论文
共 36 条
  • [1] Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males
    Borrás, C
    Sastre, J
    García-Sala, D
    Lloret, A
    Pallardó, FV
    Viña, J
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 2003, 34 (05) : 546 - 552
  • [2] INVIVO PROTECTION BY THE AMINOTHIOL WR-2721 AGAINST NEUTRON-INDUCED CARCINOGENESIS
    CARNES, BA
    GRDINA, DJ
    [J]. INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1992, 61 (05) : 567 - 576
  • [3] Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage
    Carpenter, M
    Epperly, MW
    Agarwal, A
    Nie, S
    Hricisak, L
    Niu, Y
    Greenberger, JS
    [J]. GENE THERAPY, 2005, 12 (08) : 685 - 693
  • [4] *CTR DRUG EV RES, STAT ASP DES AN INT
  • [5] *CYT STAT SOFTW SE, STATXACT 8 OV
  • [6] Epperly M.W., 2003, GENE THER MOL BIOL, V7, P61
  • [7] Epperly MW, 2002, RADIAT RES, V157, P568, DOI 10.1667/0033-7587(2002)157[0568:MSDSIR]2.0.CO
  • [8] 2
  • [9] Epperly MW, 2001, RADIAT RES, V155, P2, DOI 10.1667/0033-7587(2001)155[0002:MORICE]2.0.CO
  • [10] 2