Premium
Manganese superoxide dismutase‐plasmid/liposome (MnSOD‐PL) administration protects mice from esophagitis associated with fractionated radiation
Author(s) -
Epperly Michael W.,
Kagan Valerian E.,
Sikora Christine A.,
Gretton Joan E.,
Defilippi Stacy J.,
BarSagi Dapha,
Greenberger Joel S.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1023
Subject(s) - liposome , superoxide dismutase , glutathione peroxidase , glutathione , microbiology and biotechnology , lipid peroxidation , biology , superoxide , antioxidant , biochemistry , enzyme
Intraesophageal administration of manganese superoxide dismutase‐plasmid/liposome (MnSOD‐PL) prior to single fraction radiation has been shown to protect mice from lethal esophagitis. In our study, C3H/HeNsd mice received fractionated radiation in two protocols: (i) 18 Gy daily for four days with MnSOD‐PL administration 24 hr prior to the first and third fraction, or (ii) 12 Gy daily for six days with MnSOD‐PL 24 hr prior to the first, third, and fifth fraction. Control radiated mice received either no liposomes only or LacZ (bacterial β‐galactosidase gene)‐plasmid/liposome (LacZ‐PL) by the same schedules. We measured thiol depletion and lipid peroxidation (LP) in whole esophagus and tested the effectiveness of a new plasmid, hemagglutinin (HA) epitope‐tagged MnSOD (HA‐MnSOD). In fractionation protocols, mice receiving MnSOD‐PL, but not LacZ‐PL (200 μl of plasmid/liposomes containing 200 μg of plasmid DNA), showed a significant reduction in morbidity, decreased weight loss, and improved survival. Four and seven days after 37 Gy single fraction radiation, the esophagus demonstrated a significant increase in peroxidized lipids and reduction in overall antioxidant levels, reduced thiols, and decreased glutathione (GSH). These reductions were modulated by MnSOD‐PL administration. The HA‐MnSOD plasmid product was detected in the basal layers of the esophageal epithelium 24 hr after administration and provided significant radiation protection compared to glutathione peroxidase‐plasmid/liposome (GPX‐PL), or liposomes containing MnSOD protein, vitamin E, co‐enzyme Q10, or 21‐aminosteroid. Thus, MnSOD‐PL administration significantly improved tolerance to fractionated radiation and modulated radiation effects on levels of GSH and lipid peroxidation (LP). These studies provide further support for translation of MnSOD‐PL treatment into human esophageal radiation protection. © 2001 Wiley‐Liss, Inc.