Chromium(VI)-induced nuclear factor-kappa B activation in intact cells via free radical reactions.
Incubation of chromium(VI) [Cr(VI)] with cultured Jurkat cells resulted in activation of DNA binding activity of the nuclear factor (NF)-kappa B. In a combination with glutathione reductase, a Cr(VI) reducing agent, Cr(VI) expressed an enhanced activity in induction of NF-kappa B. This activation of NF-kappa 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-kappa 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. H2O2 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-kappa B in vitro via Cr(IV)-mediated free radical reactions. We hypothesize that Cr(VI)-mediated NF-kappa B activation may be involved in the mechanism of Cr(VI)-induced carcinogenicity.
Ye
J
J
Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD 21702, USA.
Zhang
X
X
Young
H A
HA
Mao
Y
Y
Shi
X
X
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D005561:Formates / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D008223:Lymphoma; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011192:Potassium Dichromate / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013113:Spin Labels; D014407:Tumor Cells, Cultured
D003497:Cyclic N-Oxides; D005561:Formates; D016166:Free Radical Scavengers; D005609:Free Radicals; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D015375:Receptors, Interleukin-2; D013113:Spin Labels; C030544:formic acid; D017665:Hydroxyl Radical; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D011192:Potassium Dichromate