Modulation of topoisomerase activities by tumor necrosis factor

Document Type

Article

Publication Date

1995

Abstract

A number of chemotherapeutic agents which inhibit the DNA topoisomerases markedly potentiate cell death mediated by tumor necrosis factor, suggesting a role for these enzymes in the TNF cytotoxic mechanism. To investigate this possibility, topoisomerase I and II activities were assayed following TNF addition to murine L929 cells. Topoisomerase I and II activities increased within 15 min of TNF addition and returned to baseline levels within 1 and 2 hr, respectively. The increases in both topoisomerase activities were blocked by H-7 (but not H-8) and similar increases were seen following PMA addition. However, concentrations of H-7 which blocked the increased topoisomerase activities had no effect on TNF cytotoxicity nor on the enhancement of TNF cytotoxicity by topoisomerase inhibitors. Thus, in these cells topoisomerase activities are directly modified by TNF during the initial phases of a cytotoxic response. However, neither TNF cytotoxicity nor the enhancement of TNF cytotoxicity by topoisomerase inhibitors appears to require the TNF-mediated increases in topoisomerase activities. © 1995.

Publication Title

Cellular immunology

Volume

160

Issue

1

First Page

98

Last Page

103

Comments

This article was published in Cellular immunology, Volume 160, Issue 1, Pages 98-103.

The published version is available at http://dx.doi.org/10.1016/0008-8749(95)80014-A.

Copyright © 1995.

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