The first systematic study on the roles of O-2 in the reactions of Cr(VI/V/IV) with major intracellular reductants, cysteine (1), glutathione (2), and ascorbic acid (3) as well as with vitamin E analogue Trolox (4), has been performed. The reactions of 1-3 with Cr(VI) (aqueous buffer solutions, pH = 4.5-7.5, 25 degrees C) led to a slow O-2 consumption (measured by a Clark oxygen electrode). The reactions of 1-3 with the relatively stable Cr(V) and Cr(IV) 2-ethyl-2-hydroxybutanoato complexes under the same conditions were accompanied by fast O-2 consumption. The O-2 consumption during the reactions of Cr(VI/V/IV) with 1-3 did not lead to a significant accumulation of H2O2 (determined with catalase). No significant O-2 consumption was detected for the reactions of Cr(VI/V/IV) with 4. To reveal the mechanisms of O-2 activation, the kinetics of the Cr(V/IV) reactions with 1-4 at pH 4.5 and 7.5 were studied by stopped-flow UV-visible spectrophotometry; and the kinetic data were processed by the global analysis method. The stoichiometries and products of these reactions were studied by UV-visible, CD, and EPR spectroscopies. The proposed mechanism of O-2 activation includes oxidations of 1-4 by Cr(V/IV) to produce organic radical intermediates, which then react with O-2 in chain processes. No evidence was found for the direct activation of O-2 by the Cr compounds. Implications of the proposed mechanism to the DNA damage induced by the Cr(VI) + reductant + O-2 systems have been discussed.