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Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity.

Open access
Goossens, V, Grooten, J, De Vos, K, Fiers, W·1995·Proceedings of the National Academy of Sciences

Abstract

Tumor necrosis factor (TNF) is selectively cytotoxic to some types of tumor cells in vitro and exerts antitumor activity in vivo. Reactive oxygen intermediates (ROIs) have been implicated in the direct cytotoxic activity of TNF. By using confocal microscopy, flow cytometry, and the ROI-specific probe dihydrorhodamine 123, we directly demonstrate that intracellular ROIs are formed after TNF stimulation. These ROIs are observed exclusively under conditions where cells are sensitive to the cytotoxic activity of TNF, suggesting a direct link between both phenomena. ROI scavengers, such as butylated hydroxyanisole, effectively blocked the formation of free radicals and arrested the cytotoxic response, confirming that the observed ROIs are cytocidal. The mitochondrial glutathione system scavenges the major part of the produced ROIs, an activity that could be blocked by diethyl maleate; under these conditions, TNF-induced ROIs detectable by dihydrorhodamine 123 oxidation were 5- to 20-fold higher.

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Metadata

Authors
Goossens, V, Grooten, J., De Vos, K., & Fiers, W.
Venue
Proceedings of the National Academy of Sciences
Published
1995-08-29
Volume
92
Issue
18
Pages
8115-8119
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1964390988
Cited by
596
References
0
FWCI
8.88
Type
journal article
Language
en
Open access
green

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