Evidence for a Fenton-Type Mechanism for the Generation of ·OH Radicals in the Reduction of Cr(VI) in Cellular Media

"Electron spin resonance (ESR) spectroscopy has been employed to· examine the role of tetraperoxochromate( V) ions (Cro:-) and other Cr(V) species in the generation of hydroxyl (OH) radicals in the reaction of Cr(VI) with H2O 2 in biological media. In contrast to earlier suggestions, the present ESR studies using crystalline K3CrO8 as a source of Cro:- show that decomposition of Cro:- in water or in H2O 2 does not generate significant amounts of OH radicals. Addition of NADH to a solution containing Cro:- yields a Cr(V)-NADH complex, which readily reacts with H2O 2 to generate OH radicals. Similar results obtained from several other biological reductants, including vitamin B2 , indicate that a vacant coordination site on a Cr(V) complex facilitates its reaction with H2O 2 to generate ""OH radicals. We thus suggest that in biological media, reaction [3] instead of [1] or [2] is the major pathway for the OH radical generation: While the carcinogenic potential of Cr(Vl)-based compounds has been well established via epidemiologic and animal studies (1), the underlying biochemical mechanism is still not well understood (2). In a recent development, however, Kawanishi et al. (3) have reported that hydroxyl (OH)2 radicals might be the key species in the mechanism of Cr(VI) toxicity. As to the mechanism of the ""OH radical formation they suggest that Cr(VI) reacts with cellular hydrogen peroxide (H2O 2) to form the tetraperoxochromate(V) (Crog-) ions, which decompose to produce hydroxyl radicals. It was also suggested (3) that the ""OH radicals thus produced cause genotoxicity via DNA base modification and deoxyribose phosphate backbone alterations. More recently Aiyar et al. (4) reported the detection of OH radicals in the reaction of Cr(VI) with H2O 2 in biological media, including the reaction of ""OH radicals with deoxyguanosine to generate 8-hydroxydeoxyguanosine adducts, confirming that ""OH radicals could indeed play a significant role in the mechanism of Cr(VI) toxicity. However, the mechanism for the ""OH generation was not clarified, although the role of Crog- ions as possible precursors was mentioned, somewhat along the lines suggested by Kawanishi et al. (3). The possibility of the participation of Crog- in the ""OH generation has also been indicated by Sugiyama et al. (5), since they mention that vitamin B2 enhances the formation of""OH radicals in the reaction of Cr(VI) with H2O 2 because of the generation of Crog- in the reaction."