Chromium(vi)-induced nuclear factor-k{cyrillic}b activation in intact cells via free radical reactions

Jianping Ye, Xiaoying Zhang, Howard A. Young, Yan Mao, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

Incubation of chronuum(VI) [Cr(VI)] with cultured Jurkat cells resulted in activation of DNA binding activity of the nuclear factor (NF)-k{cyrillic}B. In a combination with glutathione reductase, a Cr(VI) reducing agent, Cr(VI) expressed an enhanced activity in induction of NF-k{cyrillic}B. This activation of NF-k{cyrillic}B was decreased by a metal chelator, diethylene triaminepentaacetic acid or catalase, but increased by superoxide dismutase. Addition of Mn2+ which reacts with Cr(IV) and inhibits Cr(IV)-mediated hydroxyl radical (OH) generation via Fenton-like reaction, attenuated the activation of NF-k{cyrillic}B. Sodium formate, an OH radical scavenger, also inhibited the activation. Electron spin resonance measurements showed that the incubation of Cr(VI) with intact Jurkat cells generated reactive Cr(V) intermediate. Glutathione reductase and NADPH enhanced Cr(V) generation. Electron spin resonance spin trapping measurements using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent provided evidence that the incubation of Cr(VI) with the Jurkat cells in the presence of glutathione reductase generated OH radicals. H enhanced OH radical generation and also enhanced Cr(V) formation, indicating the role of Cr(IV) in OH radical generation. We conclude that Cr(VI) can activate NF-f{cyrillic}B in vitro via Cr(IV)-mediated free radical reactions. We hypothesize that Cr(VI)-mediated NF-k{cyrillic}B activation may be involved in the mechanism of Cr(VI)-induced carcinogenicity.

Original languageEnglish
Pages (from-to)2401-2405
Number of pages5
JournalCarcinogenesis
Volume16
Issue number10
DOIs
StatePublished - Oct 1995

ASJC Scopus subject areas

  • Cancer Research

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