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 resulte d in activation of DNA binding activity of the nuclear factor (N kappa )-kappa B. In a combination with glutathione reductase, a Cr(VI) reduc ing agent, Cr(VI) expressed an enhanced activity in induction of NF-ka ppa B. This activation of NF-kappa B was decreased by a metal chelator , diethylenetriaminepentaacetic acid or catalase, but increased by sup eroxide dismutase. Addition of Mn2+, which reacts with Cr(IV) and inhi bits Cr(IV)-mediated hydroxyl radical ((OH)-O-.) generation via Fenton -like reaction, attenuated the activation of NF-kappa B. Sodium format e, an (OH)-O-. radical scavenger, also inhibited the activation. Elect ron spin resonance measurements showed that the incubation of Cr(VI) w ith intact Jurkat cells generated reactive Cr(V) intermediate. Glutath ione reductase and NADPH enhanced Cr(V) generation. Electron spin reso nance spin trapping measurements using 5,5-dimethyl-1-pyrroline N-oxid e (DMPO) as a spin trapping agent provided evidence that the incubatio n of Cr(VI) with the Jurkat cells in the presence of glutathione reduc tase generated (OH)-O-. radicals, H2O2 enhanced (OH)-O-. radical gener ation and also enhanced Cr(V) formation, indicating the role of Cr(IV) in (OH)-O-. radical generation. We conclude that Cr(VI) can activate MF-kappa B in vitro via Cr(IV)-mediated free radical reactions, We hyp othesize that Cr(VI)-mediated NF-kappa B activation may be involved in the mechanism of Cr(VI)-induced carcinogenicity.