Generation of free radicals by Cr(IV) from lipid hydroperoxides and its inhibition by chelators.

The generation of free radicals by Cr(IV) from lipid hydroperoxides was investigated by ESR spin trapping. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Reaction of Cr(VI) with ascorbate was used as a source of Cr(IV). Incubation of Cr(VI) with ascorbate generated Cr(IV) and Cr(V). Addition of cumene hydroperoxide generated DMPO/R adduct with an enhancement of Cr(V) signal. Addition of Mn(II), whose function is to remove Cr(IV), caused dose-dependent inhibition of DMPO/R formation. Similar results were obtained using t-butyl hydroperoxide. Metal ion chelators, deferoxamine, 1,10-phenanthroline and diethylenetriaminepentaacetic acid inhibited DMPO/R formation in the order of deferoxamine > 1,10-phenanthroline > diethylenetriaminepentaacetic acid. The results suggest the possible role of Cr(IV) and its mediated free radical generation from lipid hydroperoxides in the mechanism of Cr(VI) carcinogenesis.