Reduction of chromium(VI) and its relationship to carcinogenesis

Although Cr(VI)-containing compounds are well-documented carcinogens, their mechanism of action is still not well understood. Recent studies have suggested that reduction of Cr(VI) to its lower oxidation states and related free-radical reactions play an important role in carcinogenesis. This article summarizes recent studies on (1) the reduction of Cr(VI) by 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 kappa B.