title: Inhibition of oxygen-dependent radiation-induced damage by the nitroxide superoxide dismutase mimic, tempol.
abstract: Stable nitroxide radicals have been previously shown to function as superoxide dismutase (SOD)2 mimics and to protect mammalian cells against superoxide and hydrogen peroxide-mediated oxidative stress. These unique characteristics suggested that nitroxides, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), might protect mammalian cells against ionizing radiation. Treating Chinese hamster cells under aerobic conditions with 5, 10, 50, and 100 mM Tempol 10 min prior to X-rays resulted in radiation protection factors of 1.25, 1.30, 2.1, and 2.5, respectively. However, the reduced form of Tempol afforded no protection. Tempol treatment under hypoxic conditions did not provide radioprotection. Aerobic X-ray protection by Tempol could not be attributed to the induction of intracellular hypoxia, increase in intracellular glutathione, or induction of intracellular SOD mRNA. Tempol thus represents a new class of non-thiol-containing radiation protectors, which may be useful in elucidating the mechanism(s) of radiation-induced cellular damage and may have broad applications in protecting against oxidative stress.
authors.affiliation: Radiobiology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: J B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: W
authors.initials: W
authors.lastname: DeGraff
authors.forename: D
authors.initials: D
authors.lastname: Kaufman
authors.forename: M C
authors.initials: MC
authors.lastname: Krishna
authors.forename: A
authors.initials: A
authors.lastname: Samuni
authors.forename: E
authors.initials: E
authors.lastname: Finkelstein
authors.forename: M S
authors.initials: MS
authors.lastname: Ahn
authors.forename: S M
authors.initials: SM
authors.lastname: Hahn
authors.forename: J
authors.initials: J
authors.lastname: Gamson
authors.forename: A
authors.initials: A
authors.lastname: Russo
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D006224:Cricetinae; D003497:Cyclic N-Oxides / Q000378:metabolism / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D003497:Cyclic N-Oxides; D012333:RNA, Messenger; D011837:Radiation-Protective Agents; D013113:Spin Labels; D013482:Superoxide Dismutase; D005978:Glutathione; D010100:Oxygen; C001803:tempol