The use of N-t-butyl hydroxylamine for radioprotection in cultured cells and mice.
Exposure of cells to ionizing radiation leads to formation of reactive oxygen species (ROS) that are associated with radiation-induced cytotoxicity. Therefore, compounds that scavenge ROS may confer radioprotective effects. Recently, it has been shown that the decomposition product of the spin-trapping agent alpha-phenyl-N-t-butylnitrone (PBN), N-t-butyl hydroxylamine (NtBHA), mimics PBN and is much more potent in delaying ROS-associated senescence. We investigated the protective role of NtBHA against ionizing radiation in U937 cells and mice. Viability and cellular oxidative damage reflected by lipid peroxidation, oxidative DNA damage and protein oxidation were significantly lower in the cells treated with NtBHA when the cells were exposed to ionizing radiation. The modulation of cellular redox status was more pronounced in control cells compared with NtBHA-treated cells. The ionizing radiation-induced mitochondrial damage reflected by the altered mitochondrial permeability transition, the increase in the accumulation of ROS and the reduction of ATP production was significantly higher in control cells compared with NtBHA-treated cells. NtBHA administration before irradiation at 5 mg/kg daily for 2 weeks provided substantial protection against killing and oxidative damage to mice exposed to whole-body irradiation. These data indicate that NtBHA may have great application potential as a new class of in vivo, non-sulfur containing radiation protector.
Lee
Jin Hyup
JH
Department of Biochemistry, College of Natural Sciences and College of Medicine, Kyungpook National University, Taegu 702-701, Korea.
Kim
In San
IS
Park
Jeen-Woo
JW
D000818:Animals; D002470:Cell Survival; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006898:Hydroxylamines / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013997:Time Factors; D020298:U937 Cells
D006898:Hydroxylamines; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D013113:Spin Labels; C072771:N-tert-butylhydroxylamine; D005978:Glutathione; D010100:Oxygen