Journal Article

The use of <i>N-t</i>-butyl hydroxylamine for radioprotection in cultured cells and mice

Jin Hyup Lee, In San Kim and Jeen-Woo Park

in Carcinogenesis

Volume 25, issue 8, pages 1435-1442
Published in print August 2004 | ISSN: 0143-3334
Published online August 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh139
The use of N-t-butyl hydroxylamine for radioprotection in cultured cells and mice

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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 α-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.

Keywords: CMAC, t-butoxycarbonyl-Leu-Met-7-amino-4-chloromethylcoumarin; DCFH-DA, 2′,7′-dichloro-fluoroscin diacetate; DHR, dihydrorhodamine; DNP, dinitrophenyl; DPPP, diphenyl-1-pyrenylphosphine; FACS, fluorescence-activated cell sorter; FITC, fluorescein isothiocyanate; HNE, 4-hydroxynonenal; MBA, malondialdehyde; MPT, mitochondrial membrane potential transition; NtBHA, N-t-butyl hydroxylamine; 8-OH-dG, 8-hydroxy-2′-deoxyguanosine; PBN, α-phenyl-N-t-butylnitrone; ROS, reactive oxygen species; TBARS, thiobarbituric acid-reactive substances; TRITC, tetramethylrhodamine isothiocyanate

Journal Article.  5617 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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