Mechanisms of chromium Genotoxicity† ‡

Hexavalent chromium(VI) is genetically active in intact cells, but inactive in simplified systems (isolated nuclei, purified DNA). Chromate ions are transported through cell membranes by a gene‐controlled mechanism. The reduction within the cytoplasm leads mainly to chromium inactivation, although formation of genetically active chromium(III) complexes cannot be ruled out. Interactions with the genetic material are referred to unreduced chromium(VI) and, most of all, to chromium(III) complexes originated by intracellular reduction of chromium(VI). Trivalent chromium(III) is inactive in intact cells, but active in simplified systems. Chromium(III) complexes do not permeate cell membranes, except in particular conditions, in which genetic effects are observed. Mechanisms of chromium genotoxicity are revised: Interference of chromium with nucleotide biosynthesis. Structural alterations of the genetic material, stimulating DNA‐repair. Reduced fidelity of DNA synthesis (due to reaction of chromium(III) with DNA). Preferential sites of point mutations, role of DNA repair mechanisms, interactions with other genotoxic agents, putative thresholds, genetic effects in vivo (particularly in humans), correlations between mutagenicity and carcinogenicity, and environmental aspects are discussed. In the conclusions possible developments for future research are analysed.