Cr(Ⅵ)-containing compounds are well-established carcinogens, although the mechanism for chromium-induced carcinogenesis is still not well understood. The reduction of Cr(Ⅵ) to its lower oxidation states, particularly Cr(Ⅴ) and Cr(Ⅳ), is an important step for the production of chromium-mediated reactive oxygen species(ROS). The persistent oxidative stress during the reduction process may play a key role in the mechanism of Cr(Ⅵ)-induced carcinogenesis. This paper summarizes recent studies on (1) the reduction of Cr(Ⅵ) to Cr(Ⅲ) occur by a multiplicity of mechanisms depending on the nature of reducing agents including ascorbate, diol-and thiol- containing molecules, certain flavoenzymes, cell organelles, intact cells, and whole animals; (2) free-radical production with emphasis on hydroxy radical generation via Fenton or Haber-Weiss type reactions; and (3) free radical-induced cellular damage, such as DNA strand breaks, hydroxylation of 2'-deoxyguanosine, and activation of nuclear transcription factor κB.
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