The principal mechanism of H2O2 toxicity is thought to involve the generation of hydroxyl (HO.) radicals through its interactions with Fe2+ ions by the Fenton reaction. Of particular interest has been the demonstration by Ward, Blakely & Joner [(1985) Radiat. Res. 103, 383-392] that the cytotoxicity of H2O2 is diminished at low temperature. We have now examined this phenomenon further with a mammalian epithelial cell line (CNCMI-221). Resistance of these cells to 100 microM-H2O2 added extracellularly exhibits a transition in the temperature range between 27 degrees C and 22 degrees C. We have found that the low-temperature resistance to cytotoxic concentrations of H2O2 is abolished by preincubation of cells with reductants such as ascorbate or reduced lipoic acid. This implies that the low-temperature resistance to H2O2 cytotoxicity may be due to inhibition of cellular reductive processes. The restoration of the cytotoxic action of H2O2 at 4 degrees C by ascorbate is prevented by pre-exposure of cells to desferrioxamine. This is evidence that transition-metal ions (such as iron ions) are involved in the cytotoxicity and is consistent with a mechanism of cell damage that depends on the Fenton reaction and a metal ion in the reduced state. Restoration of H2O2 cytotoxicity at low temperature by ascorbate is consistent with the artificial production of an intracellular reducing environment that at normal temperatures is sustained by cellular metabolism.
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Research Article|
December 15 1989
Hydrogen peroxide cytotoxicity. Low-temperature enhancement by ascorbate or reduced lipoate
S K Jonas;
S K Jonas
*Department of Chemical Pathology, University College and Middlesex School of Medicine, Cleveland Street, London W1P 6DB, U.K.
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P A Riley;
P A Riley
*Department of Chemical Pathology, University College and Middlesex School of Medicine, Cleveland Street, London W1P 6DB, U.K.
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R L Willson
R L Willson
†Department of Biochemistry, Brunel University, Uxbridge, Middx. UB8 3PH, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1989 London: The Biochemical Society
1989
Biochem J (1989) 264 (3): 651–655.
Citation
S K Jonas, P A Riley, R L Willson; Hydrogen peroxide cytotoxicity. Low-temperature enhancement by ascorbate or reduced lipoate. Biochem J 15 December 1989; 264 (3): 651–655. doi: https://doi.org/10.1042/bj2640651
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