A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells.
Organisms exposed to ionizing radiation are mainly damaged by free radicals, which are generated by the radiolysis of water contained in the cells. Recently a significant reduction of tissue injury from irradiation damage was demonstrated by using MnSOD-plasmid/liposome treatments in the protection of murine lung. In this study we show that a new active recombinant human MnSOD (rMnSOD), easily administered in vivo, not only exerts the same radioprotective effect on normal cells and organisms as any MnSOD, but it is also radiosensitizing for tumor cells. In addition, we show how healthy animals, exposed to lethal doses of ionizing radiation and daily injections with rMnSOD, were protected from radiodamage and were still alive 30 days after the irradiation, while animals treated with only PBS solution, in the absence of rMnSOD, died after 7-8 days from the radiotreatments. The molecular analysis of all irradiated tissues revealed that the antiapoptotic AVEN gene appeared activated only in the animals treated in the presence of rMnSOD. The data suggest that rMnSOD deserves to be considered as a pharmaceutical tool for making radiotherapy more selective on cancer cells and to prevent and/or cure the accidental damage derived from exposure to ionizing radiation.
Borrelli
Antonella
A
Department of Molecular Biology and Biotherapy, National Cancer Institute of Naples, Italy.
Schiattarella
Antonella
A
Mancini
Roberto
R
Morrica
Brunello
B
Cerciello
Vincenzo
V
Mormile
Maria
M
d'Alesio
Valentina
V
Bottalico
Laura
L
Morelli
Francesco
F
D'Armiento
Maria
M
D'Armiento
Francesco Paolo
FP
Mancini
Aldo
A
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D045744:Cell Line, Tumor; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000494:pharmacology; D005609:Free Radicals / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007928:Lethal Dose 50; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D011832:Radiation Injuries / Q000517:prevention & control; D011836:Radiation Tolerance / Q000187:drug effects; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000494:pharmacology
C412506:AVEN protein, human; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D016166:Free Radical Scavengers; D005609:Free Radicals; D008565:Membrane Proteins; D011838:Radiation-Sensitizing Agents; D011994:Recombinant Proteins; D013482:Superoxide Dismutase