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Carcinogenesis Advance Access published online on March 11, 2004

Carcinogenesis, doi:10.1093/carcin/bgh139
© 2004 by Oxford University Press
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© 2004 Oxford University Press

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

The use of N-t-butyl hydroxylamine for radioprotection in cultured cells and mice

Jin Hyup Lee 1, In San Kim 2, and Jeen-Woo Park 1*

1 Department of Biochemistry, College of Natural Science, Kyungpook National University, Taegu 702-701, Korea
2 College of Medicine, Kyungpook National University, Taegu 702-701, Korea

* Corresponding author. E-mail: parkjw{at}knu.ac.kr.

Received 24 December 2003 ; revised 9 February 2004 ; accepted 27 February 2004

Abstract

Exposure of cells to ionizing radiation leads to formation of reactive oxygen species that are associated with radiation-induced cytotoxicity. Therefore, compounds that scavenge reactive oxygen species may confer radioprotective effects. Recently, it has been shown that the decomposition product of the spin-trapping agent {alpha}-phenyl-N-t-butylnitrone, N-t-butyl hydroxylamine (NtBHA), mimics {alpha}-phenyl-N-t-butylnitrone and is much more potent in delaying reactive oxygen species-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 to NtBHA-treated cells. The ionizing radiation-induced mitochondrial damage reflected by the altered mitochondrial permeability transition, the increase in the accumulation of reactive oxygen species, and the reduction of ATP production was significantly higher in control cells compared to 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.


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